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55209977 | Mass-Based Investigation of Particle Volatility Mass-based particle volatility was investigated with the TGA to evaluate the mass fraction of volatile and nonvolatile substances in the particulate samples collected on filter papers installed inside the MOUDI.The brake specific emissions of volatile and non-volatile substances at different size bins are shown in Fig. 3 for the engine load of 0.7 MPa, and the MMD and geometric standard deviation for the non-volatile substances are listed in Table 4.For PM 1.8 , the brake specific emissions of volatility substances are 64.2,55.2 and 132.6 mg/kWh for biodiesel, ULSD and LSD, respectively, indicating that using biodiesel, the emission of volatile substances could reduce, compared with LSD, but could increase, compared with ULSD.However, in terms of mass fraction, biodiesel particles contain 32.2% volatile substances which is larger than 13.8 and 23.0% for ULSD and LSD particles, respectively.Chang et al. (1998) suggested that due to its lower volatility (higher boiling point), unburned biodiesel fuel should be more likely to condense and adsorb on the soot particles, leading to higher volatile fraction on these particles.Ballesteros et al. (2008) attributed the higher volatile fraction in biodiesel particles to their higher surface/volume ratio.The higher surface/ volume ratio implies an increment in the active surface in which the hydrocarbons can be adsorbed and causes a rise in the volatile fraction.Moreover, oxygenated fuels like biodiesel have significant effect on the reduction of soot. On the other hand biodiesel might also lead to a reduction in hydrocarbon emissions which might reduce the volatile fraction.Further analysis shows that, with biodiesel, the non-volatile substances in PM 1.8 decrease by 69.7 and 60.9%, compared with LSD and ULSD, respectively, while for volatile substances, the corresponding reductions are 51.6% and -16.3%.It indicates more effective reduction on non-volatile substances than volatile substances.The LSD particles contain a larger percentage of volatile substances than the ULSD particles.Liu et al. (2005) suggested that higher fuel sulfur content results in higher concentration of nucleated sulfuric acid particles, which provides larger amount of sites for the condensation of volatile organic compounds. The size resolved particle volatility is compared among the three fuels in Fig. 3.For particles with aerodynamic size less than 180 nm, the brake specific emissions of volatile substance are 40.9 and 25.7 mg/kWh, respectively, for biodiesel and ULSD, while for particles with aerodynamic size between 180-1800 nm, the corresponding values are 23.4 and 29.5 mg/kWh.It indicates that the higher brake specific emission of volatile substances from biodiesel is mainly in the smaller size bins.Fig. 3 also shows that the brake specific emission of volatile substances from LSD is larger than those from biodiesel and ULSD in all the size bins. Fig. 4 shows the mass fraction of volatile substances at different aerodynamic size bins for the three fuels at the engine load of 0.7 MPa.For each fuel, the mass fraction of volatile substances first decreases with the particle size and then increases.The decrease of volatile fraction with particle size in the small-size range (for particles less than 100 nm in diameter) has been found by Kwon et al. (2003) who conducted an experimental investigation on particulate emissions of a medium-sized diesel truck mounted on a chassis dynamometer.It is known that nucleation mode particles with diameter less than 50 nm are mostly formed from volatile hydrocarbon or sulfuric acid in the dilution process, thus these particles contain a higher mass fraction of volatile substances.On the other hand, particles with much larger size have fractal-like structure which provides more pores and intra-particle cavities for the condensation and adsorption of volatile substances (Kerminen et al., 1997;Ristovski et al., 2006), leading to an increase of the volatile fraction in these particles.Similar result was also found by Kerminen et al. (1997) and Zhang et al. (2009) who used low-pressure impactor in their investigations.In this study, for the three fuels, biodiesel particles contain the highest mass fraction of volatile substances in the smallsize range.In the large-size range, LSD particles exhibit stronger volatility because the larger amount of large-size LSD particles promotes the adsorption and condensation of volatile substances. | 5 |
55209977 | Particle Number Concentration, Size Distribution and Volatility Number-based particle concentration, size distribution and volatility were investigated using the SMPS and the TD, with the TD set to 275°C.The particles measured with the SMPS alone contain both non-volatile and volatile substances while those measured with the SMPS and the TD contain non-volatile substances only with the volatile substances being adsorbed in the TD.Typical number concentration and size distributions measured with and without the TD are shown in Fig. 5 for the engine load of 0.38 MPa, while the influence of engine load and fuel on particle geometrical mean diameter (GMD) is shown in Fig. 6.The number concentrations measured with the SMPS can be converted into brake specific particle number concentrations (BSPN) and the results are shown in Fig. 7 for different engine loads, with and without the TD. Fig. 5 shows that the LSD and biodiesel, respectively, generate the highest and the lowest number of particles, both with and without the TD.The difference among the different fuels is mainly due to difference in particles larger than 50 nm in diameter.Number-based particle volatility was investigated using the SMPS measurements, with and without the TD.Basically, particles measured with the SMPS with the TD are non-volatile ones.As shown in Fig. 5, the loss of particles associated with the TD is mainly concentrated on particles which are less than 100 nm in size, especially for the biodiesel and ULSD.With the TD, some of the particles may be completely adsorbed if they are completely composed of volatile substances, while some of them may shrink in size to form particles with diameter less than 10 nm (Rönkkö et al., 2007).In this study, particles below 10 nm could not be measured because the SMPS measurement was set to 10-486 nm.However, particles above 100 nm in size are less affected by the TD.Alander et al. (2004) suggested that accumulation mode particles mostly exist in the form of primary particle agglomerates and the volatile substances may be collected in pores and intra-particle cavities between the primary particles.Thus the mobility size of the accumulation mode particles is not significantly influenced by the removal of the volatile substances. Fig. 6 shows that the GMD increases with engine load for each fuel which is a consequence of the increase in mass of fuel burned in the diffusion combustion mode at high engine load (Tsolakis, 2006;Zhu et al., 2010;Srivastava1 et al., 2011).The high fuel/air ratio and local temperature associated with high engine load also promote particle formation.Moreover, at high engine load, the time available for soot oxidation after the end of the diffusion combustion period is shorter, leading to the formation of a larger number of particles (Tsolakis, 2006).With more particles being formed, they tend to coagulate to form larger particles.Furthermore, during the dilution and cooling of the exhaust gas, the volatile substances could condense on the surface of the existing particles to form larger ones (Bagley et al., 1998;Schneider et al., 2005).This effect is more significant at high engine load when the exhaust gas temperature is higher (Ning et al., 2004).Fig. 6 also shows that, with the TD, there is an increase in the GMD of the particles.On average of the different engine loads, the GMDs increased by 13.5, 12.3 and 10.4% for the biodiesel, LSD and ULSD, respectively, which could be attributed to the higher level of volatility in the small size particles.Biodiesel has a higher level of volatility in the small size particles, hence, the adsorption of the smaller particles lead to a larger increase in GMD, after passing through the TD, compared with the two diesel fuels.Fig. 7 shows that in general, with and without the TD, for each fuel, the BSPN firstly decreases with the increase of engine load and then increases, which is similar to the results of the mass-based BSPM (Fig. 2).A comparison on the results, obtained without the TD, shows that the BSPN is the highest for LSD and the lowest for biodiesel, for all the engine loads.On average of the five engine loads, with biodiesel, the BSPN is decreased by 19% and 47%, compared with ULSD and LSD, respectively.Besides a reduction in BSPN, there is also a corresponding reduction in the GMD.For the biodiesel, the explanations for its lower BSPM and MMD could also be applied to explain the lower BSPN and GMD.Fig. 7 shows both the BSPN obtained with and without the TD.If the BSPN obtained without the TD is considered as a combination of non-volatile and volatile particles, and the BSPN obtained with the TD represents the non-volatile particles, the difference between them can be used as an indication of the BSPN of volatile particles.The BSPN thus obtained is presented in Fig. 8(a) while Fig. 8(b) shows the fraction of the BSPN of volatile particles in the BSPN obtained without the TD.As shown in Fig. 8(a), for each fuel, the BSPN of volatile particles firstly decreases with the increase of engine load and then increases, which is consistent with the trend of BSPN in Fig. 7. Fig. 8(a) shows that the biodiesel particles contain a higher BSPN of volatile particles than the ULSD particles at almost all engine loads while the LSD particles contain the highest level of volatile particles, which is in line with the results obtained in the mass-based investigation on volatile particles.On average of the five engine loads, the BSPNs of volatile particles are 2.00 × 10 14 , 1.25 × 10 14 , and 3.76 × 10 14 #/kW h for biodiesel, ULSD and LSD respectively.However, the volatile particles occupy 52.3%, 40.0% and 58.7% in the total particle emissions at the engine load 0.7 MPa, for the biodiesel, ULSD and LSD, respectively, which is larger than the corresponding reduction in the mass fraction of volatile substances especial for the biodiesel and LSD.One of the reasons is that a portion of the volatile substances exists as nanoparticles which contribute significantly to number concentration reduction but much less to the mass concentration reduction. In regard to the number-fraction of volatile particles, as shown in Fig. 8(b), the minimum percentage of volatile particles occurs at the intermediate engine load for the biodiesel and ULSD.For example, for biodiesel, there is 44.2% volatile particle in total BSPN at 0.38 MPa, while the corresponding percentages at 0.08 and 0.7 MPa are 51.9% and 52.3%, respectively.However, for the LSD, the percentage of volatile particles exhibits monotonic increase with engine load.At low engine load, due to lower incylinder gas temperature, there is a larger amount of unburned hydrocarbon and lubricating oil in the exhaust gas which could be converted to volatile particles or condense on existing soot agglomerates (Ning et al., 2004;Ristovski et al., 2006;Mustafi et al., 2010), leading to an increase in particle volatility.The increase in volatility under high engine load is uncommon but has also been observed by Meyer and Ristovski (2007) through a VH-TDMA (volatilization and humidification tandem differential mobility analyzer) investigation on emissions from a six-cylinder diesel engine fueled with commercial 500-ppm-wt sulfur diesel fuel.Meyer and Ristovski (2007) suggested that ternary nucleation involving sulfuric acid, water and ammonia might be the dominant mechanism for production of volatile substances at high engine load.Therefore, in this study, the ternary nucleation might be one of the dominant mechanisms for the formation of volatile substances when the engine is fueled with the LSD. | 6 |
55209977 | Particle Number Concentration and Volatility in Different Size Groups Nanoparticles (< 50 nm) are more hazardous to human health (Peters et al., 1997;Somers et al., 2004).Thus, the particles are classified into three groups: < 50, 50-100 and > 100 nm, for further analysis.The effect of fuel type and engine load on the BSPN and fraction of the particles in each of the three size groups is shown in Fig. 9. Compared with ULSD, the BSPN of biodiesel is at similar level for particles < 50 nm but lower for the larger particles, indicating that the reduction of BSPN associated with the biodiesel is concentrated on large size particles.In comparison with LSD, biodiesel and ULSD could lead to reduction of BSPN in all size groups, and LSD has the lowest fraction of small size particles while biodiesel has the highest.The volatility of particles in different size groups is also investigated.For different size groups, the BSPN of volatile particles and their percentage in the total volatile particles are shown in Fig. 10.On average of the five engine loads, in the size group of < 50 nm, the BSPNs of volatile particles are 1.38 × 10 14 , 8.64 × 10 13 and 2.02 × 10 14 #/kW h for biodiesel, ULSD and LSD respectively.The results indicate that the biodiesel could reduce the volatile particles in the small size range, compared with LSD but leads to an increase, compared with ULSD.The number-fractions of volatile particles in the size group of < 50 nm are 57.6,35.7 and 59.5% for biodiesel, ULSD and LSD, respectively.The number fraction of volatile particles is similar between biodiesel and LSD in this size range.While for the size group of > 100 nm, the number-fractions of volatile substances are 31.3,15.2 and 42.9%, for biodiesel, ULSD and LSD, respectively.LSD particles exhibit obviously higher number-fraction of volatile substances than those from the biodiesel and ULSD.The higher volatility of the LSD particles in the large-size range is in line with the mass-based results.However, there might be different mechanisms leading to these results as a consequence of the different methods used to assess the mass-based and number-based volatile fractions.In the mass-based case, it is assessed based on the loss of adsorption and condensed volatile substances upon heating in the TGA.In the numberbased method, the volatile substances are adsorbed in the TD instead of being adsorbed or condensed on the soot particles, leading to a reduction of particle sizes and reflected in the change of BSPN, in particular for the LSD which generates a larger amount of large-size particles.Both the number-based and mass-based results show that the volatile substances in the LSD particles are distributed over a wider range of size than the biodiesel and ULSD particles. | 7 |
54729029 | In this paper the mathematical model describing the falling thin liquid film on a vertical wall is considered taking into account heat and mass transfer at the interface in the regime of periodic rolling waves. The families of exact and numerical generalized solutions, where periodic traveling waves conjugate through the strong and weak discontinuities with each other or with the residual thickness, are constructed. Evolution of exact periodic generalized solutions is studied in time. 1 Problem statement Heat transfer at condensation of immobile saturated vapor on a vertical surface was firstly considered in [1] for the case of the laminar flow of a condensate film. Later, theoretical and experimental studies of the film flows, including those with consideration of heat and mass transfer on the free surface, were carried out in many papers. It is shown [2] that the Kapitza waves are not the capillary, but the rolling ones. A possibility of traveling wave existence on the surface of a vertically falling liquid film without consideration of surface tension is shown in [3], and the equation, describing propagation of these waves, so-called kinematic equation, is also derived there (exact discontinuous solutions to this equation correspond qualitatively to the experimental results). In [4], the flow of a thin liquid film on a vertical wall was studied theoretically with consideration of condensation at the interface in the regime of the rolling waves. The families of discontinuous solutions were derived, where the traveling waves conjugate with each other or with a residual thickness through strong and weak discontinuities. In [5] the model that takes into account heat and mass transfer at the interface of a thin film of liquid flowing down a vertical wall in the regime of rolling waves for both cases – evaporation and condensation was studied. The full families of exact generalized solutions, which model the increasing and decreasing waves as well as the rolling waves, where the traveling waves are interfaced through strong or weak discontinuities with each other or with the “residual” thickness were constructed. Time evolution of these families of exact generalized solutions was studied. The maps of flow regimes of the liquid film on a vertical heat transfer surface were plotted. Based on the model developed in [3-5], the traveling waves on the surface of a falling liquid film were studied in [6], taking into account heat and mass transfer and surface tension. * Corresponding author: [email protected] DOI: 10.1051/ 01075 (2016) , 2016 72 7201075 HMTTSC MATEC Web of Conferences matecconf/2016 © The Authors, published by EDP Sciences. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (http://creativecommons.org/licenses/by/4.0/). In this paper, we consider the model that takes into account heat and mass transfer at the interface of a thin film of liquid flowing down a vertical wall in the regime of periodic rolling waves for both cases – evaporation and condensation. We have constructed the exact generalized solutions, which model the increasing and decreasing waves as well as the periodic rolling waves, where the traveling waves are conjugated through strong or weak discontinuities with each other or with the “residual” thickness. The rolling wave equation was obtained in [5] | 1 |
54729029 | Problem statement Heat transfer at condensation of immobile saturated vapor on a vertical surface was firstly considered in [1] for the case of the laminar flow of a condensate film.Later, theoretical and experimental studies of the film flows, including those with consideration of heat and mass transfer on the free surface, were carried out in many papers.It is shown [2] that the Kapitza waves are not the capillary, but the rolling ones.A possibility of traveling wave existence on the surface of a vertically falling liquid film without consideration of surface tension is shown in [3], and the equation, describing propagation of these waves, so-called kinematic equation, is also derived there (exact discontinuous solutions to this equation correspond qualitatively to the experimental results).In [4], the flow of a thin liquid film on a vertical wall was studied theoretically with consideration of condensation at the interface in the regime of the rolling waves.The families of discontinuous solutions were derived, where the traveling waves conjugate with each other or with a residual thickness through strong and weak discontinuities.In [5] the model that takes into account heat and mass transfer at the interface of a thin film of liquid flowing down a vertical wall in the regime of rolling waves for both casesevaporation and condensation was studied.The full families of exact generalized solutions, which model the increasing and decreasing waves as well as the rolling waves, where the traveling waves are interfaced through strong or weak discontinuities with each other or with the "residual" thickness were constructed.Time evolution of these families of exact generalized solutions was studied.The maps of flow regimes of the liquid film on a vertical heat transfer surface were plotted.Based on the model developed in [3][4][5], the traveling waves on the surface of a falling liquid film were studied in [6], taking into account heat and mass transfer and surface tension. In this paper, we consider the model that takes into account heat and mass transfer at the interface of a thin film of liquid flowing down a vertical wall in the regime of periodic rolling waves for both casesevaporation and condensation.We have constructed the exact generalized solutions, which model the increasing and decreasing waves as well as the periodic rolling waves, where the traveling waves are conjugated through strong or weak discontinuities with each other or with the "residual" thickness. The rolling wave equation was obtained in [5] 3 3 where h is the liquid film thickness, and the coefficients are determined in the following manner: . This is the rolling wave equation, which considers the capillary forces ( D > 0) and condensation at 0 4•10 6 J/kg.Calculation gives the values D =4.6•10 -5 , E 1.The discontinuous solutions to equation ( 1), limit at 0 D o , are the stable generalized solutions to hyperbolic equation 3 1 3 The similar equation was derived in [5]. | 2 |
54729029 | Periodic solution of equation of the rolling wave at phase transition The hyperbolic equation ( 2) admits exact solution 2 ( , , ) 2 describes a change in initial film thickness (0, ) condensation, the film thickness increases, and at 0 E , i.e., at evaporation, the film thickness decreases.We will derive the exact solutions, which model evolution of a single rolling wave at 0 E , i.e., at evaporation.These solutions are set by formula and they are presented [5] by increasing h and decreasing h waves, traveling with velocities V and V , conjugated with depths ( , , ) , ) through weak discontinuities on lines ( ) x a t and ( ) x c t , where ( , , ), 0 ( , ), ( , , ) 0, ( , ). Here, 2 ( , ) / (2| |) T K E K E is time, required for complete evaporation of the residual layer with initial depth K .It follows from formulas (3)-( 4) that complete evaporation of the residual layer from the left of the rolling wave, i.e., at ( ) x a t d , occurs at ( , ) l T K E , and from the right of this wave, i.e., at ( ) We will study time evolution of infinite succession of waves of type (3) rolling in the residual layer ( , , ) H t K E , where l r K K K , in the regime of evaporation at 0 E .We assume that the initial amplitude of these waves is relatively small.To set the initial position of rolling wave succession, we consider section * * , and expand solution (3), limited in this section, to periodic solution ( , ) In the case of condensation, i.e., at 0 E ! , time evolution of infinite succession of waves of type (3) rolling in the residual layer ( , , ) | 3 |
98253702 | A síntese de uma série de álcoois secundários derivados da (R)-carvona, assim como o curso estereoquímico da esterificação destes derivados com (±)-ibuprofeno é apresentada. O composto comercial racêmico foi transformado nos respectivos ésteres diastereoisoméricos através do acoplamento mediado por DCC/DMAP, fornecendo o par de diastereoisômeros derivados de (S)ou (R)-ibuprofeno em relação até 5.7:1, dependendo do tipo de auxiliar quiral empregado. | 1 |
98253702 | Introduction During the past two decades, the preparation of optically active drugs has received considerable attention both, from academics and industry.The reasons behind this interest are threefold, including the medical benefit from using a single chemical entity, the changing pharmaceutical regulations, which now require the development of optically active drugs as single stereoisomers, and also advances in strategies for the synthesis of optically pure compounds, which facilitated the task. 1 Ibuprofen (1, Figure 1) is a non-steroidal antiinflammatory agent of the class of the a-arylpropionic acids, which also includes flurbiprofen (2, Figure 1), fenoprofen (3, Figure 1), ketoprofen (4, Figure 1) and naproxen (5, Figure 1), amongst its most prominent members.The drug is marketed mostly as the racemate despite that it has been shown that the (S)-enantiomer is the main responsible for the therapeutic effect.The pure enantiomer is also available, being prescribed only for certain specific conditions. 2t has been demonstrated that (R)-ibuprofen as well as its congeners can be stereoselectively interconverted in vivo into their active enantiomers through a thioester-mediated epimerization process which involves the Co-enzyme A (CoA). 3 However, these acyl-CoA thioester derivatives are chemically reactive and may become involved in a transacylation reactions with endogenous nucleophiles, leading to covalent binding of the drug to proteins, the clinical consequences of which relate to the toxicity of this pharmaceutically active ingredient. 4It is also suspected that the acyl-CoA intermediate derived from (R)-ibuprofen may be responsible for the formation of mixed glyceryl esters, which once deposited in fatty tissue could cause unknown long-term effects, transforming (R)-ibuprofen into a pharmacological uncertainty. 5herefore, the selective preparation of (S)-ibuprofen has been the subject of intense research and numerous stereoselective chemical approaches have been explored for that purpose. 6In addition, resolutions of the racemate by means of crystallization of diastereomeric salts, 7 as well as chemoenzimatic transformations including esterificacion, trans-esterification, 8 enantioselective hydrolysis of esters, 9 amides 10 and nitriles 11 and other enzyme-mediated strategies, 12 and a yeast-mediated selective degradation of the unwanted enantiomer, 13 have also been reported. Carvone is a naturally-occurring cyclohexylic terpenoid which is isolated from Carum carvi, Anethum graveolans and Mentha spicata, being available in both of its enantiomeric forms.It has been extensively employed as building block in organic synthesis. 14Interestingly, however, the use of carvone derivatives as chiral auxiliaries has only few and scattered precedents. 15he chiral auxiliary-mediated dynamic kinetic resolution of a-substituted carboxylic acids has been recently recognized as an approach towards the preparation of enantioenriched a-aminoacids, as well as their a-mercapto-, a-haloand a-hydroxycongeners.This is an effective alternative, provided configurational lability can be induced at the stereogenic a-carbonyl center. 16ecently, Amoroso and coworkers 17,18 reported the preparation of different a-arylpropionic acids in their enantioenriched forms, by using lactamide-type chiral auxiliaries.The diastereomeric mixtures of the corresponding lactamic esters were obtained in good yields and reasonable diastereoselectivities depending upon the solvent and chiral auxiliary used.Therefore, here we wish to report the synthesis of chiral secondary alcohols derived from (R)-carvone (6, Figure 1) and their reaction with racemic ibuprofen under Steglich conditions, 19 as a stereodivergent entry to enantioenriched mixtures of esters derived from either (S)-or (R)-ibuprofen, depending on the type of chiral auxiliary employed. | 2 |
98253702 | Results and Discussion Three series of secondary alcohols were prepared.In the first one, (R)-carvone was submitted to a conjugate addition reaction with thiophenol under thermodynamic conditions, 20 furnishing thioethers (7a-c, Scheme 1) in 4, 34 and 16% yield, respectively.On the other hand, reaction with PhSH and 2-naphthalenethiol under kinetic 21 conditions afforded sulfides (7a and 8, Scheme 1) in 60 and 92% yield, respectively. The stereochemistry of these products was deduced by comparison with literature data, 22 analysis of the enhancement of signals in nuclear Overhauser effect (nOe) experiments and examination of their 1 H NMR spectra, which revealed that H-3 was considerably more deshielded in 7a (d 3.89 ppm) than in 7b (d 2.91 ppm) and 7c (d 3.29 ppm), pointing out to a pseudo-axial orientation of the heteroatomic substituent.The preferential generation of 7a and 8 under kinetic conditions is consistent with an axial Michael addition of the thiols from the a-face of carvone, driven by stereoelectronic effects, and subsequent protonation of the resulting enolate from the opposite and less hindered b-face.Compounds 7b and 7c may result from the base-mediated equilibration of 7a under the reaction conditions. 23iastereoselective reduction of ketones 7a, 7b and 8 with K-Selectride in anhydrous THF, 24 from the less encumbered b-face of their corresponding carbonyl moiety, 25 provided alcohols 9a, 9b and 10 (Scheme 1) in 58, 66 and 56%, respectively. For the second series, where the aromatic substituent is directly attached to a cyclohexenic six-membered ring, (R)-carvone was subjected to the direct addition of three different Grignard reagents.The procedure stereoselectively furnished alcohols 15a-c (Scheme 2), as result of an antiperiplanar attack of the Grignard reagent with respect to the isopropenyl group. 27In turn, these tertiary allylic alcohols were treated with PCC/Al 2 O 3 , producing an oxidative allylic transposition 28 to the corresponding 3-phenyl-(S)-carvone derivatives 16a-c (Scheme 2) in yields ranging from 71 to 86%. 29 Figure 1.Chemical structures of (±)-ibuprofen (1), other relevant a-arylpropionic acid type non-steroidal anti-inflammatory agents (2-5) and R-carvone (6).Vol.21, No. 6, 2010 These ketones were stereoselectively reduced with sodium borohydride in a MeOH-THF mixture, furnishing the secondary allylic alcohols 17a-c (Scheme 2) in 83-94% yield.Their configuration was determined as 1S,5S based on literature precedents 30 and the results of a nOe experiment, where signal enhancement of H-5 was observed upon irradiation of H-1. | 3 |
98253702 | Me The third group of chiral alcohols was obtained after subjecting (R)-carvone to conjugate addition reactions with aryl and 1-naphthyl Grignard reagents in the presence of copper(I) iodide 31 to which TMSCl was added in order to ensure efficient transformations. 32ese gave the corresponding silyl enol ether intermediates 18a and 18b (Scheme 3) in high yields, as single diastereomers to which the (3S,5R)-configuration was assigned on the basis of literature precedents, 33 an exhaustive NMR analysis of 18b and knowledge of the role of the isopropenyl group in determining the stereochemistry of the conjugate addition product.The stereochemical result of this reaction is consistent with the outcome of the reductions of ketones 16a-c, resulting from a nucleophilic attack anti-periplanar to the bulky isopropenyl group. In turn, these were desilylated by careful treatment with TBAF in Et 2 O in order to avoid the production of diastereomeric mixtures at the stereocenter adjacent to the carbonyl, due to the base-catalyzed epimerization of the initial product. 34In this process, protonation of the trapped intermediate enolate from the less hindered face anti-periplanar to the C-5 substituent, furnished ketones 19a and 19b (Scheme 3) in 96 and 90% yields, respectively.Finally, ketones 19a,b were stereoselectively reduced with K-selectride to the corresponding secondary alcohols 20a and 20b (Scheme 3) in 80% yield.Interestingly, the stereochemical outcome of the reduction was different from that previously observed with the sulfur-containing alcohols and could be attributed to a different preferred conformation of the starting ketones, where the bulky aryl substituents are located equatorially, flipping the isopropenyl moiety to a pseudo-axial position, thus hindering the approach of the reducing agent from the side of the isopropenyl group. This speculation was confirmed by nOe experiments on 19a and 19b, which revealed that irradiation of the methylene carbon of the isopropenyl moiety excerted signal enhancement of H-3 (Figure 2).On the other hand, detection of H-3 signal enhancement in 20a upon irradiation of the C-2 methyl group and also of H-9b confirmed that they were located on the same side of the molecule.Furthermore, the axial nature of the hydroxyl group was established from the values of the coupling constants between H-1 and its neighbours in its 1 H NMR spectrum (4.5 and 5.9 Hz) and its lack of nOe signal enhancement of H-1 upon irradiation of H-9b. The performance of the chiral auxiliaries was evaluated through their submission to esterification reactions with (±)-ibuprofen, under the conditions described by Steglich, 19 which employ the DCC-DMAP reagent system as condensing agent. As shown in Table 1, alcohol 9a provided up to a 28:72 mixture of diastereomeric esters in 89% combined yield, when the reaction was carried out in CHCl 3 at -50 ºC (entry 1).Furthermore, when the bulkier 2-naphthyl thioether 10 was used as chiral auxiliary, a slight improvement in the diastereomeric ratio (26:74) was observed, at the expense of a slight decrease in yield of product (entry 10).On the other hand alcohol 9b, a diastereomer of 9a, furnished essentially equimolecular mixtures of diastereomeric esters (entries 4-9), according to NMR and HPLC peak area integration, regardless the solvent and temperature conditions employed. In an attempt to improve the product diastereomeric ratio, the reactions with the related sulfoxide 13 and sulfone 14 were explored.However, essentially no chiral induction was observed among the resulting esters (entries 11-14). Chiral auxiliaries 17a-c gave diastereomeric ratios nearing 2:1 (Table 2), always favouring the same ester which as discussed below, was demonstrated to be that derived from (S)-ibuprofen.The best results in terms of chemical and optical yields were obtained with alcohol 17a, when subjected to esterification in toluene at -20 ºC (entry 3). When chiral alcohols 20a and 20b were subjected to esterification with (±)-ibuprofen under Steglich conditions (Table 3), it was observed that the best results were obtained when chloroform was employed as solvent (entries 1, 2 and 13) and that the product was enantioenriched in the ester derived from (R)-ibuprofen.Comparison with esters prepared with pure (S)-ibuprofen indicated that the major diastereomer is that derived from (R)-ibuprofen.Interestingly, slightly improved diastereomeric ratios were obtained when a five-fold excess of ibuprofen was employed, while changing the order of addition of the reagents, preincubation of a mixture of the acid and the alcohol with activated 4Å molecular sieves and the addition of triethylamine (entries 3-5) did not improve the diastereomeric ratios of ester products. In addition, a trend was observed, indicating that the bulkier 1-naphthyl derivative 20b slightly outperformed its congener 20a, probably by leading to a chiral auxiliary with a conformationally more rigid cyclohexyl ring.Under the typical conditions, a ratio of products up to 82:18 was observed (entry 13).These levels of enantioenrichment are similar to those previously informed by the group of Amoroso. 17or the sake of comparison, the effect of placing a bulkier group near the secondary alcohol was examined with (-)menthol (31, Scheme 4), the esterification of which with (±)-ibuprofen in CHCl 3 at 0ºC gave 55% of a nearly 1:1 mixture of diasteromeric esters 32 (Scheme 4). The group of Amoroso has demonstrated that ibuprofen and other a-substituted carboxylic acids undergo a dynamic kinetic resolution process when subjected to the Steglich esterification. 19As shown in Scheme 5, when an a-substituted carboxylic acid (I) reacts with DCC and DMAP, enantiomeric acyl-DMAP derivatives II and III are formed as intermediates.Under these conditions, it has been proposed that the stereogenic center becomes labile and the enantiomeric acyl-DMAP derivatives are thus capable of being interconverted.When a chiral alcohol (R*OH) is added to the reaction medium, both acyl-DMAP intermediates can react to furnish diastereomeric ester products (IV and V).Two main conditions are required for a successful dynamic kinetic resolution.One of them is that interconversion between the acyl-DMAP derivatives II and III should proceed at a faster rate than formation of the ester products and the other is that the acyl-DMAP intermediates should react at very different rates with the chiral auxiliary. In order to gain further understanding on the studied esterification, a series of esterifications were carried out with pure (S)-ibuprofen.After examination of the products, it was observed that when the reaction was carried out with alcohol 20a the resulting major diastereomers where those carrying the (R)-configuration on the ibuprofen a-carbonyl stereocenter.On the contrary, when the esterifications where carried out with alcohols 17a-c, the prevailing diastereomers were those derived from (S)-ibuprofen (Tables 1-3).However, composition of the mixtures was different from those arising from the racemic acid, pointing out to poor compliance of the studied transformations with the requirements for a successful dynamic kinetic resolution.Particularly, the experiments revealed that interconversion of the enantiomeric acyl-DMAP intermediates is not fast enough, compared with their reaction with the chiral auxiliary, to grant a more optically efficient transformation. In conclusion, it was demonstrated that secondary alcohols derived from naturally-occurring (R)-carvone are able to provide good yields of enantioenriched mixtures of ibuprofen esters, that their performance is similar to that of other chiral alcohols and that depending on the chosen chiral auxiliary, production of (R)-or (S)-ibuprofen derived esters may be favoured. | 4 |
98253702 | Experimental Melting points were taken on an Ernst Leitz Wetzlar model 350 hot-stage microscope and are reported uncorrected.Specific rotation data were obtained with a Jasco DIP 1000 photopolarimeter, fitted with 1 dm cells.FT-IR spectra were determined employing a Shimadzu Prestige 21 spectrophotometer as solid dispersions in KBr disks, or as thin films held between NaCl cells.The 1 H and 13 C NMR spectra were acquired in CDCl 3 in a Bruker Avance spectrometer (300.13 and 75.48 MHz for 1 H and 13 C, respectively), with tetramethylsilane (TMS) as internal standard.The chemical shifts are reported in ppm downfield from TMS and coupling constants (J) are given in Hertz.DEPT 135 and DEPT 90 experiments aided the interpretation and assignment of the fully decoupled 13 C NMR spectra.In special cases, 2D-NMR (COSY, HMBC, HMQC and J-resolved spectra) and selective nOe experiments were also employed.Pairs of signals marked with "#", " ‡" or with an asterisk, "*", as superscripts indicate that their assignments may be exchanged. In the conventional work-up procedure, the reaction was diluted with brine (5-10 mL) and the products were extracted with EtOAc (4-5 × 20 mL).The combined organic extracts were then washed once with brine (5 mL), dried over Na 2 SO 4 and concentrated under reduced pressure.The residue was submitted to flash column chromatography with silica gel 60 H. Elution was carried out with hexane-EtOAc mixtures, under positive pressure and employing gradient of solvent polarity techniques. All new compounds gave single spots on TLC plates run in different hexane-EtOAc and CH 2 Cl 2 -toluene solvent systems.Chromatographic spots were detected by exposure to UV light (254 nm), followed by spraying with ethanolic ninhydrin (amines) or with ethanolic p-anisaldehyde/ sulfuric acid reagent and careful heating of the plates for improving selectivity. The diastereomeric esters of ibuprofen were best separated on a Varian ProStar liquid chromatograph fitted with a 250 × 4.6 mm C-18 Luna column (Phenomenex, 5 mm particle size), using a 80:20 mixture of MeOH:50 mmol L -1 phosphate buffer, pH 5.5 as mobile phase, pumped at 1 mL min -1 .Detection wavelength was 254 nm. | 5 |
98253702 | S , 3 R , 5 R ) -5 -I s o p r o p e n y l --m e t h y l -3phenylcyclohexanone 19a: CuI (500 mg, 2.64 mmol) was added to a stirred 1.18M THF solution of PhMgBr (8 mL, 5.28 mmol), cooled to 0 ºC.After stirring 15 min, a solution of (R)-carvone (209 mg, 1.39 mmol) and TMSCl (772 mg, 7.1 mmol) in THF (2 mL) was introduced dropwise and the reaction was further stirred 45 min at 0 ºC.Then, the mixture was treated with saturated NH 4 Cl and the reaction products were extracted with EtOAc (4 × 50 mL).The combined organic extracts were washed with brine (10 mL), dried (Na 2 SO 4 ) and concentrated under reduced pressure.The resulting residue was filtered through a short plug of silica gel, furnishing 18a (380 mg, 96%), as a yellowish oil.Without further purification, a stirred solution of the silyl ether 18a (100 mg, 0.35 mmol) in Et 2 O (10 mL) was cooled to 0 ºC and treated with 1M TBAF in THF (0.42 mL, 0.42 mmol).After 2 h at this temperature, the volatiles were removed under reduced pressure and the residue was chromatographed affording ketone 19a (72 mg, 95%), as a pale yellow oil.[a] D 25 -55. | 6 |
98253702 | Table 2 . Esterification a Deduced by comparison with esters prepared with pure (S)-ibuprofen. 1 H enone 16c: 18% PCC on Al 2 O 3 (1.09g, 0.91 mmol) was added portionwise to a solution of alcohol 15c (98 mg, 0.38 mmol) in anhydrous CH 2 Cl 2 (15 mL), and the resulting suspension was stirred 1 day at room temperature.The solids were separated by filtration through Celite and the filter was washed with CH 2 Cl 2 (3 × 10 mL). | 8 |
225649150 | Chalcone is one of the phenolic group secondary metabolic with numerous biological activities. Many studies have shown that chalcone derivatives compound has anti-cancer, anti-inflammatory, antimalarial, and antibacterial activities. The purpose of this research was to study the prediction potency unsaturated carbonyl system of chalcone derivative against HeLa cell by MTT assay. Those activities assumed can inhibit the mechanism action of NF-kB that caused cervical cancer. The 2,4-dihydroxide-4’methoxychalcone has done synthesis as a target compound by a sonochemical for 7 hours. The results showed that chalcone derivative most active against the HeLa cell. | 1 |
225649150 | Introduction Cancer is a disease caused by abnormal and uncontrolled cell growth (Anwar et al., 2018). In its development, cancer cells can spread to other parts of the body and end in death. In general, the cause of cancer cannot be ascertained. Various factors both genetic and environmental factors (Shanmugam et al., 2016) have a certain contribution to increasing the risk of cancer. Various types of cancer, including breast cancer and cervical cancer, are contributors to sufficient mortality, tragically, cervical cancer is one of the most cancer that diagnosed among woman (Bak et al., 2016), however, new drug and new technologies or all-combined have been allowed as solve a problem (Bedell et al., 2020). Treatment efforts in terms of dealing with cancer certainly continue. Given the predicted increase in the surge in cancer patients by 300 percent worldwide in 2030 with a quantity of 70 percent in developing countries including Indonesia. Based on the Ministry of Health data, the prevalence of cancer can reach 4.3 to 1,000 people. For 2020, about 13,800 new cases of cervical cancer diagnosed in women between 35 until 44 ages year old and 4,290 women die caused cervical cancer based on The American Cancer Society's estimates. Chalcone as flavonoids classes of plant-derived compounds containing than 4000 secondary metabolites (Syed et al., 2016) which several biological effects, in recent years, have biochemical and pharmacological as well as anti-cancer (Alper et al., 2019). Flavonoids as a natural product such as oxorylin A, wogoni, and vitexin were reported for the treatment of cancer diseases and undergoing phase I/II clinical trials in China (Liu et al., 2020). The conjugation, hydroxylation, and substitutions in the chemical structure of chalcone derivates may give significant biological activities and flavonoids classes were bearing hydroxyl group and double bond of ring recently designed synthesized as biochemical properties as against cancer (Hoang et al., 2015). Various treatments for many types of cancer, chemotherapy surgery, radiotherapy, or combinations, however, multidrug resistance happens in some cases. The development of another new drug for design and discovery needs to solve the problem (Abbas et al., 2019). Chalcone is an important anti-cancer agent that discovery in the synthesized drug-using mechanism of cytotoxic activity of chalcone included by apoptosis, cell cycle disruption, inhibition of tubulin polymerization, blockade of nuclear factor-kappa B and inhibition of kinases for cervical cancer cell (Abbas et al., 2019). Nuclear factor-kappa B (NF-kB) one of the transcription factors as a molecular target that critical factors and important studies intervention biological, pharmacological and development new drug since they involved in the control of immune responses that causes cancer diseases (Kaneko et al., 2019). The aim of the study was to predicted and investigate of the compound that obtained by hydroxyl and unsaturated carbonyl system in chemical structure in term of anti-cancer by blockade nuclear factor-kappa B (NF-kB) that the first classical pathway (Escárcega et al., 2007) induced genes. This general structure of synthesized is shown in Figure 1. and cytotoxic properties shown by the MTT assay data as a cytotoxic assay that used directly (Abel & Baird, 2018) to determine cell viability. In Vitro anti-cancer, HeLa cells (Luong et al., 2017) (human cervical cancer) in this research were culture in Roswell Park Memorial Institute (RPMI) from Parasitology Laboratory, Universitas Gadjah Mada. The procedure was started in RPMI, 100 mL of cell suspension containing 106 cells was added into microplate 96 each well and incubated for 24 h at 37 0 C and 5% CO2. A test chalcone compound solution was inserted into a cell suspension that had been incubated previously. Added 100 mL of RPMI and cancer cells in wells as media and cell control. After the incubation, the culture media was removed and washed by PBS, then MTT solution of 100 mL (9.5 mL of RPMI and 1 mL of MTT solution) was inserted into wells and incubated again for 4 h with the same condition. 100 mL of 10% SDS in 0,1 N HCl as stopper reaction added into each of wells. Next, the wells left at room temperature overnight were wrapped by paper tightly. Then, absorbance reading by ELISA reader at 595 nm (wavelength optimum) and Percentage of survival cells were determined and calculated by eq. 1. The compound of 2,4-dihydroxide-4'-methoxychalcone has been synthesized by (Suryani et al., 2019) with yield product 98 %, respectively. Sonochemical method using to achieve optimal yield and this method an alternative to a short time reaction of synthesis. Methanol as a solvent (Figure 1) for synthesis growth a yield as good as possible and evaporated easily. The result showed that the sonochemical method was efficient (Monsef et al., 2020) since the conventional method needs a long time reaction for 24-72 hours. Figure 1. General one-pot synthesis method with reagents; 1) acetophenone, 2) benzaldehyde and product; 3) 2,4-dihydroxide-4'-methoxychalcone Chalcone compound was identified by spectral data IR, EI-MS, 1 H, and 13 C-NMR (Suryani et al., 2019). By 1 H-NMR, H with 7,44 ppm and H 7,86 ppm with doublet peak (J = 15 Hz) described the unsaturated carbonyl of chalcone were performed. That peak with chemical shift was specific for unsaturated carbonyl of chalcone. Furthermore the chemical shift of H presenced downfield since resonance by electronwithdrawing side with H . Hence we assumed that activity in vitro of chalcone against a panel of human cervical cell lines (HeLa) by applying 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) assay as the most popular assessment of viability and cytotoxicity (Pascua-Maestro et al., 2018). Chalcone has an active compound as inhibition of cell growth with IC50 value less than 20 g/mL, moderate active with IC50 value 20-100 g /mL and not active in the inhibition of cell growth if IC50 value than 100 g /mL (Anwar et al., 2018). Based on IC50 references, chalcone synthesized has moderate activity with IC50 (percentage at which 50% of HeLa cells are dead) value shown in Table 1, but that activity of the compound is not selective because of that activity against normal cell (Vero) by 42,29 g /mL with the low selectivity index 0,57. | 2 |
225649150 | Discussion Chalcone compound, 2,4-dihydroxide-4'-methoxychalcone was prepared by the Claisen-Schmidt according to Scheme 1. To obtain chalcone in good yield, the residues were treated with 10 % in methanol. The synthesis compound was evaluated for its activity as anti-cancer by showed IC50 value may be influenced to such factors like the nature of substitutions in the ring of chalcone, the genetic and biochemical specific compound (Solomon & Lee, 2012). Based on Table 1, it showed that the IC50 value chalcone derivative is 74,24 g/mL with 0,57g/mL of selectivity index. The IC50 value calculated, represents that the concentration of the result in a 50 % decrease in cell growth since the chalcone compound is the most widely known as anti-cancer agents. The range as moderate activity, the chalcone compound showed as generally better against HeLa cell lines cancer. The addition of the hydroxyl group at positions 2 and 4 in ring A may affect the activity cancel line inhibitor, also the methoxy group presence increases inhibitory activity too. As a whole, chalcone structure consists of two aromatic rings (A and B) (Han et al., 2019) with disubstituted of a hydroxyl group in ring A and monosubstituted of methoxy in ring B (Mahapatra et al., 2015) have activities moderate level since that substituted important as active site (Venkateswararao et al., 2012). Moreover, it was also has a double bond opening ring of benzene. Accordingly, the chalcone compound should undergo mechanism investigation to understand the active sites as potentially more drug agents. Nuclear factor-kB (NF-kB) one of a key role in cancer disease (Folmer et al., 2008), then as a subunit of the transcription factor in cancer cells, NF-kB, controlled immune responses, proliferation, apoptosis and tumorigenesis (Wu et al., 2019). Investigated of chalcone, particularly that hydroxyl group in the aromatic ring did not give a significant activity (Zhang et al., 2018), but unsaturated carbonyl of chalcone predicted inhibiting the activity of transcription activity in an uncontrolled cell (Bazzaro et al., 2011) From Scheme 2, unsaturated carbonyl of chalcone attacked by Ik-kB, that it was IKK protein-mediated of the NF-kB activation pathway (Yadav et al., 2011). Based on the mechanism reaction of Scheme 2, bonding between protein Ik-kB and unsaturated carbonyl of chalcone may stop NF-kB pathway as caused proliferation of cancer cells in humans. As a candidate drug, a mechanism the activity chalcone assumed by blocked the NF-kB pathway was identified since the in-vitro MTT assay test. In other particularly research, the hydroxyl group of chalcone as flavonoid metabolic secondary, interaction too with Ik-kB of human and it useful to synthesis a novel drug (Moulishankar & Lakshmanan, 2020). When we treat cancer cases, activation of NF-kB should be blocked and the Ik-kB activation pathway did not bind with NF-kB when unsaturated carbonyl bind with Ik-kB than NF-kB transcription factor will be inhibited (Yoon & Rui, 2007). Despite chalcone effects, it potency (Meng et al., 2014), the active site for inhibited NF-kB was an important role in determining chalcone to docking molecular as an anti-cancer drug in future (Ren et al., 2017). To rapidly, when the compound of drug identify inhibiting the NF-kB signaling pathway currently these drugs provide have development. | 3 |
58914429 | A cathodic stripping voltammetric method for determination of Ti(IV) in water samples containing high concentrations of surfactants is described. The linear calibration plot for Ti(IV) was achieved in the simultaneous presence of 5 mg L anionic, 1 mg L cationic and 2 mg L nonionic surfactants for an accumulation time of 30 s in the range 2.5 × 10 to 5 × 10 mol L, the detection limit for accumulation time of 30 s was about 8.4 × 10 mol L. The developed method was successfully applied to Ti(IV) determination in environmental waters, such as river water (Bystrzyca, Czerniejówka), stagnant water (Lake Zemborzyce) and rain water (collected from eastern areas of Poland) with satisfactory results. | 1 |
58914429 | Introduction The excellent properties possessed by titanium make it a highly useful material.Titanium alloys have been increasingly widely used in aviation, aerospace, shipbuilding and other industrial departments whereas the main use of TiO 2 is as a white powder pigment used in products such as paints, coatings, plastics, paper, inks, fibers, food and cosmetics [Akram et al., 2011;Chunxiang et. Al., 2011].Because application of titanium has been growing steadily, the possibility of rise of its concentration in environmental water samples increases.Therefore the need for simple, cheap and sensitive procedure of titanium determination in environmental water samples grows. The electrochemical behavior of titanium makes its classical voltammetric determination very difficult, because at the common potentials it cannot be reduced to the metallic state and deposited onto an electrode.The voltammetric procedures for titanium determination are based on adsorption of the Ti(IV) complexes and next its reduction to Ti(III).For this purpose various complexing agents are exploited, e.g.mordant red, cupferron, beryllon III, pyrocatechol, calcein, xylenol orange, methylthymol blie, chromotripic acid, pyridylazoresorcinol. The analysis of titanium at the trace level in various environmental samples has been achieved by adsorptive stripping voltammetric method which is based on the formation and accumulation of complexes with chloranilic acid. However, it should be noted that although voltammetric methods are simple and sensitive, they are vulnerable to numerous interferences arising mainly from the environmental sample matrix.In voltammetric procedures even low concentrations of organic matter, inevitably present in environmental samples, limit the applicability, e.g.surfactants can foul and passive the electrode causing a decrease or total decay of the analytical signal [Hoyer and Jansen, 2003].Because production and use of surfactants has been growing steadily, their concentration in environmental water samples increases [Chebotarev et al., 2004].Therefore the need for voltammetric stripping procedures making possible the titanium determination in the presence of surfactants grows. This work provides a simple and fast procedure for determination of Ti(IV), which allows for the analysis of environmental water samples with a complicated matrix containing high concentration of nonionic, anionic and cationic surfactants.For this purpose Amberlite XAD-7 resin was used for surface active substance removing by means of their adsorption on the resin while Ti(IV) remains in the sample and it is possible to directly determine it by adsorptive stripping voltammetry. | 2 |
58914429 | E3S Web of Conferences The measurements were made using an EA-9 electrochemical analyzer and a controlled growth static mercury drop electrode in the HMDE mode, both made by MTM-ANKO Cracow, Poland.A three electrode system consisting of an Hg drop working electrode (drop surface area 1.4 mm 2 ), a Pt auxiliary electrode and an Ag/AgCl reference electrode were used.Measurements were performed using differential pulse adsorptive stripping voltammetry according to the following procedure.A natural water sample or synthetic sample for the testing procedure (containing Ti(IV) and surface active substances), 2 mL of 1 mol L -1 acetate buffer pH = 3 and an adequate volume of triply distilled water, so that the final volume of the solution was 20 mL were added to a glass vial of volume 25 mL and finally 0.5 g of XAD-7 resin was inserted.Then, a magnetic stirring bar was put into the vial, and the solution was mixed for 5 min.Next, after sedimentation of resin 9.8 mL of the solution was pipetted into the electrochemical cell and then 200 µL of 1 × 10 -2 mol L -1 chloranilic acid was added and deaeration for 5 min.was performed.A mercury drop was formed, and the accumulation of the Ti(IV)-chloranilic acid complex was carried out at -0.25 V for 60 s from the stirred solution.After the equilibration time of 5 s, the differential pulse voltammogram was recorded, while the potential was scanned from -0.25 V to -0.85 V, with the intensity of the obtained peak directly proportional to the concentration of Ti(IV) in the sample.The scan rate and pulse height were 20 mV s -1 and -50 mV, respectively. | 3 |
58914429 | The elimination of influence of nonionic surface active compounds Triton X-100 is a high-purity, water-soluble, liquid nonionic surfactant that has come to be recognized as a performance standard among similar products.Triton X-100 is widely used in numerous commercial and industrial products as a substrate for detergents, in textile and fiber manufacture because of its excellent detergency, excellent wetting ability and excellent grease and oil removal from hard surfaces [Mei-Hui, 2008].Considering such a common utilization, Triton X-100 is released into the environment in relatively great amounts.Taking this into account Triton X-100 was chosen for the examination of the influence of nonionic surface active compounds on the voltammetric titanium signal and next elimination of these interferences using XAD-7 resin. As can be observed, the voltammetric signal of titanium is very sensitive to the presence of even small amounts of the nonionic surfactant, 0.5 mg L -1 of Triton X-100 causes almost total decay of the Ti(IV) peak.The addition of resin eliminates the unwanted negative influence of the nonionic surfactant.In the presence of Amberlite XAD-7 resin inherency of even 2 mg L -1 of Triton X-100 does not affect the titanium signal at all and 5 mg L -1 of Triton X-100 causes a decrease of the titanium signal to 60 % of its original value. The elimination of influence of cationic surface active compounds Cationic surfactants are widely used in household products such as fabric softeners, hair conditioners, soaps, shampoo and other hair products.Other applications of cationic surfactants ensue from the fact that they are effective anti-bacteria agents, therefore, they are generally employed as disinfectants and antiseptic agents and are used in germicide and sanitizer products.Because of their positive charge, cationic surfactants adsorb strongly to the negatively charged surfaces of sludge, soil and sediments.The widespread use and sorption behavior of cationic surfactants implies that these substances are expected to be present in many environmental compartments [Agrawal et al., 2004].One of them is a well-established commercial synthetic cationic surfactant cetyltrimethylammonium bromide (CTAB) and it was chosen for this work. As can be observed, similarly as in the case of Triton X-100, the voltammetric signal of titanium is very sensitive to the presence of even small amounts of the cationic surfactant, 0.1 mg L -1 causes a decrease of the Ti(IV) peak to 60 % of its original value and 0.5 mg L -1 causes total decay of the titanium signal. The addition of Amberlite XAD-7 resin minimalize this negative influence.In the presence of resin inherence of even 2 mg L -1 of CTAB does not affect the titanium signal at all. | 4 |
58914429 | The elimination of influence of anionic surface active compounds Anionic synthetic surfactant sodium dodecylsulfate (SDS) was selected for this work due to its high solubility in water and first of all because it is a well-established commercial anionic synthetic surfactant.SDS is commonly used as an ingredient in household and personal care products as well as in specialized applications [Mei-Hiu L, 2008]. SDS to a lesser extent influences the voltammetric signal of titanium, 5 mg L -1 causes a decrease of the peak to 60 % of its original value.In the presence of Amberlite XAD-7 resin even 40 mg L -1 of SDS does not affect the titanium signal. | 5 |
58914429 | Environmental samples analysis Four fresh environmental water samples, such as river water (Bystrzyca, Czerniejowka), stagnant water (Lake Zemborzyce) and rain water were collected from eastern areas of Poland and Ti(IV) determination by the proposed procedure was performed.No Ti(IV) was detected in the samples in concentrations above the detection limit.To confirm the accuracy of the proposed procedure the analysed samples were spiked with Ti(IV) at different concentration levels and the titanium content was determined by the standard addition method.Three replicate determinations using the standard addition method gave average recovery values between 97.3 and 102.8 % with relative standard deviation between 4.8 and 2.6 %, what proves a satisfactory accuracy and precision of the proposed method for the determination of titanium 09006-p.2ICHMET 2012 in environmental water samples. | 6 |
195401952 | Many of the medicaments used historically in root canal treatment have been shown to be cytotoxic [1]. Toxic devitalising agents such as arsenic trioxide (As2O3), a water-soluble compound, forming arsenious acid (H3AsO4) and paraformaldehyde were commonly used in the past to devitalise inflamed pulps when effective anaesthesia could not be obtained [2]. Among these substances an important role was played by paraformaldehyde pastes. In the oral cavity paraformaldehyde agents are used both as disinfectants and to devitalise inflamed pulps when local anaesthesia is ineffective. Despite the clinical benefits paraformaldehyde is not confined to the pulp, but penetrates through dentine and is gradually released as formaldehyde. Formaldehyde released through dentine has a destructive effect on periodontal and bone tissues [3-8]. | 1 |
195401952 | Introduction Many of the medicaments used historically in root canal treatment have been shown to be cytotoxic [1]. Toxic devitalising agents such as arsenic trioxide (As2O3), a water-soluble compound, forming arsenious acid (H3AsO4) and paraformaldehyde were commonly used in the past to devitalise inflamed pulps when effective anaesthesia could not be obtained [2]. Among these substances an important role was played by paraformaldehyde pastes. In the oral cavity paraformaldehyde agents are used both as disinfectants and to devitalise inflamed pulps when local anaesthesia is ineffective. Despite the clinical benefits paraformaldehyde is not confined to the pulp, but penetrates through dentine and is gradually released as formaldehyde. Formaldehyde released through dentine has a destructive effect on periodontal and bone tissues [3][4][5][6][7][8]. Formocresol is advocated as an intracanal medicament because of its antibacterial and tissue fixative properties [9,10]. Liquid formaldehyde compounds, such as formocresol may be expressed through patent apical, lateral and accessory canals and cause soft tissue and bony injury within the periodontium [10][11][12][13]. Since the advent of effective methods of securing anaesthesia, the use of paraformaldehyde or other toxic preparats for pulp devitalization has declined [14]. However, contrary to the trends within modern endodonties, it has yet to disappear from clinical practice, being advocated in vital primary endodonties and sporadically associated with severe tissue breakdown in adults [15][16][17][18]. This article describes the effects on the periodontal and bone tissues of the paraformaldehyde used as a devitalising or disinfectant agent. | 2 |
195401952 | Advances in Dentistry & Oral Health A 20-year-old female presented to her dentist complaining of pain in the maxillary right quadrant. The practitioner elected to devitalize tooth 16, which had shown signs of pulpitis, with a paraformaldehyde-containing paste since local anaesthesia had been ineffective. Shortly after the placement of the paste, the patient experienced increasing pain and noticed that there was blackening of the gingiva (Figure 1). She was referred to Ataturk University, Department of Periodontology for advice regarding gingival necrosis associated with the distal interproximal area of tooth 16. A decision was made to attempt to preserve the tooth by root canal treatment. Oral hygiene procedures were instituted, and the necrotic tissues were removed from the area. The operative area was irrigated with saline. Root canal treatment was completed, and the patient discharged for 1 week. One week later, there was no distal gingival papilla at tooth 16 and interproximal bone was exposed to a height of approximately 2-3mm (Figure 3). At this stage a coronally repositioned flap was planned in order to remove of the necrotic tissues and to cover the root surface. A sulcular incision was performed initially and then a vertical incision was made between distal aspect of teeth 17 and 15. Exposed necrotic bone was removed with a curette and water-cooled bur. To protect the exposed bone and expedite healing, the affected area was covered with a coronally repositioned flap. The patient was reviewed to check healing. After 1 week the sutures were removed and the operative area irrigated with saline. At 1-year recall, the patient reported that the tooth was functional without any problem. Clinical examination revealed nothing abnormal -no symptoms, no detectable mobility, no periodontal pocketing. The tooth was in functional occlusion. | 3 |
195401952 | Case 2 A 35-year-old female with a history of severe pain in the left mandibular molar region was referred for assessment. The patient reported symptoms of irreversible pulpitis around from tooth 36 ( Figure 4A & 4B). His general dental practitioner was unable to obtain adequate anaesthesia to extirpate the pulp from this tooth and applied paraformaldehyde paste to effect devitalisation. Subsequently the patient stated that she experienced severe pain, the lower left molar area. She was referred to Ataturk University, Department of Periodontology for advice regarding gingival necrosis associated with the distal interproximal area of tooth 36-37. Clinical examination revealed hard, inflamed gingiva with probing depths not exceeding 3mm on the distal aspect of tooth 36. There was no measurable tooth mobility. Radiographic examination demonstrated expansion of the periodontal ligament and loss of lamina dura distal to the tooth 36. Despite all the persuasive efforts, the patient decided to extract the tooth and the tooth was extracted. | 4 |
195401952 | Discussion The primary cause of pulpal pathosis is bacterial infection. Without the presence of bacteria in the root canal system, periradicular inflammation will not develop or persist [19]. Consequently, the purpose of root canal treatment is the elimination of bacteria and their substrates from the pulp canal system. During this treatment the pulp is removed and the root canal is cleaned and shaped. Various chemicals used in medicating root canals can create adverse tissue reactions [10]. This fact, combined with the knowledge that the pulp and periodontal ligament are interconnected via accessory canals, dentinal tubules and iatrogenic communications suggests that overzealous use of intracanal medicaments can lead to deleterious effects to the host tissue with resultant postoperative discomfort [20,21]. In the past, effective anaesthesia was either unavailable or rudimentary [2]. Today there are methods of anaesthesia and reliable anaesthetic agents able to control most pulpal pain for treatment. Therefore, it is unnecessary to use chemicals for devitalising pulps. However, they are still in use and dental complications continue to be reported, even in developed countries [7,13,18]. Paraformaldehyde has well-recognised toxic effects, which predictably occur on direct contact with gingiva and bone. The recovery of paraformaldehyde from a sequestrum is an indication of the local distribution of this toxic material in the tissues [14]. In the present study toxic effects of paraformaldehyde was seen on periodontal tissues and the tooth preserved by a combination of periodontal, endodontic and maintenance therapy. | 5 |
164474492 | Amlodipine is the best-prescribed medication for cardiovascular disease major risk factor for hypertension and atorvastatin well known for diabetic. First discussed low cost ultraviolet-visible technique for the determination and quantitation of drugs in pharmaceuticals and biological fluids. Chromatographic techniques have an application with respect to trace analysis. Different types of chromatography such as high-performance liquid chromatography, high performance thin layer chromatography have most frequent applications in the field of pharmaceutical as well as biomedical analyses. Chromatography combined with mass spectrophotometry has the ability to collect molecular ion, followed to prepare a spectrum to assess molecular weight as well as structure. High-performance liquid chromatography coupled with mass spectrophotometry is a reliable and dynamic technique for the analysis of small and large drugs molecule. The advantages and disadvantages of all techniques are compared with each other with respect to sensitivity, reproducibility and other important parameters. The investigation also focused for the quantitation on both drugs in pharmaceutical preparations and plasma samples with the help of all available analytical techniques. | 1 |
164474492 | INTRODUCTION Amlodipine besylate ( fig. 1a) is scientifically known as (RS)-3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro -6-methyl-3,5-pyridinedicarboxylate benzene sulfonate. It was first introduced and prescribed for coronary artery disease. It was also helpful for angina and peripheral artery disease [1]. Now days mostly targeted for the patient having hypertension. The European Society of Cardiology was conducted survey until the year 2000 and their report based on statistical analysis showed nine hundred seventy-two million people were in this category. The number will increase with time and expected by the year 2025, approximately 1.56 billion [2]. This drug is under the umbrella of calcium channel blocker. The mechanism of such blockers to control the transportation of calcium to coronary (mainly smooth muscle) and arteries, that reflects on muscles became relaxes, reduces peripheral resistance and ultimately lowering the blood pressure [3]. Atorvastatin ( fig. 1b) is chemically known as (βR, δR)-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-lH-pyrrole-1heptanoic acid. The synthetic drug, atorvastatin is generally under the class known statins. These reductase inhibitors are familiar as 3-hydroxyl-3methylglutaryl-coenzyme A (HMG-CoA). All drugs are prescribed for cardiovascular disease and reduction of heart attack, as well as for clinical demand [4][5][6][7][8][9][10]. Active pharmaceutical ingredients (APIs) such as amlodipine are commonly manufactured as their acid addition salts to promote solubility and improve both stability and bioavailability. The objective of this review article was to research more about ultraviolet-visible and chromatographic technique's applications, specifically for the quantification of amlodipine and atorvastatin in bulk, pharmaceutical formulations, and biological fluids. Compared the result between all the developed method for amlodipine and atorvastatin about the limit of detection and quantitation value. Discussed briefly the importance of all analytical techniques with respect to cost, time of analysis, sensitivity and limitations. | 2 |
164474492 | UV-visible spectrophotometer Spectroscopic methods are mostly used for the determination of drugs in bulk as well as with pharmaceutical formulations. Ultraviolet (UV) and visible spectrophotometry are important and common techniques for the quantitative analysis of drugs. Because these are low-cost techniques, simple and no requirement of pretreatment as well as any elaborate preparatory step prior to assay. The visible spectrophotometer is depending on the redox and complex formation reaction. However, some deficiencies are also with the techniques with respect to the 6 presence of two or more drugs have similar UV characteristic. The detailed literature survey studies elaborate on the advantages and disadvantages among all developed method for both drugs using UVvisible spectrophotometer are presented in table 1. | 3 |
164474492 | High performance liquid chromatography High-performance liquid chromatography (HPLC) technique is more accurate and based on the properties of the analyte with the existing mobile phase and stationary phase. Depending on the stationary and mobile phase, different types of chromatography techniques are developed. Recently high-performance liquid chromatography has achieved lots of attention in the field of pharmaceutical analysis in dosage forms and biological fluids because of its simplicity, sensitivity and high specificity. The conventional rule for the analysis of polar compounds by utilizing a non-polar stationary phase with the polar mobile phase and vice versa for the non-polar compounds. Stationary phase binding the analyte is directly proportional with the surface area of the nonpolar segment of the analyte associate the ligand as well as with aqueous eluent. One of the main parameters found as evidence about the quality and efficacy of drug products and formulations is stability testing. The products nature is changing with humidity, temperature, light, retesting time, storage conditions, shelf life, so it is necessary to control the environmental factors. To develop method different types of the column (ODS C 18 , BDS C8, ODS C8, BDS C18 and Discovery HS C18 The ultra-performance liquid chromatography (UPLC) is a new and modern technique for liquid chromatography. Worldwide HPLC was a predominant technique for the last 30 to 40 y for the drug analysis. Speed, sensitivity, and resolution are the main keywords for the drugs analysis with UPLC compare to HPLC. The particle size can play a significant role in this type of chromatography that governed by the well-known Van Deemter equation. For UPLC, the preferred size diameter is less than 2μm to get more sensitivity, short analysis time and improved resolution. The quality of the product analyzed by UPLC will give better with less time. However, the main disadvantage is related to the column life. The analysis requiring high pressure (100 M Pa) that damage the column efficiency. The novel and selective methods were developed for the determination of both drugs with a marketed formulation as single or combined dosage form [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98] (table 3). | 4 |
164474492 | Ultra pressure liquid chromatography Thin-layer chromatography (TLC) is a simple separation technique typically for the mixture of nonvolatile compounds. The adsorbent material, specifically cellulose, silica gel, aluminum oxide is covered on plastic or glass sheet, known as the stationary phase. Aleppo bentonite with modified phenyl support can also be applied as the stationary phase, has the ability to separate amlodipine and atorvastatin with a mobile phase consisting of sodium phosphate buffer and acetonitrile (50:45, v/v) in pharmaceutical dosage form [99]. Methanol, toluene triethylamine combination and silica gel adsorbent distinct atorvastatin in pharmaceutical formulation with high resolution [100]. However, triethylamine can be replaced with chloroform and acetic acid in tablet dosage form on the aluminum plate [101]. However, propanol and water system (70:30, v/v) has the capability to separate amlodipine with a detection limit of 0.4 µg [102]. | 6 |
164474492 | 248 Bulk drug and tablets [83] High-performance thin layer chromatography High-performance thin layer chromatography (HPTLC) is an accelerated separation technique and flexible enough to determine the drug sample. The advantages associated with HPTLC are a short analysis time for the complex sample without pretreatment, independent construction of chromatogram with multiple samples, easy to transfer samples that will increase the confidence and reliability of the technique. It can be employed for qualitative and quantitative purposes. Several combinations of mobile phases with different size of plates have been successfully studied by HPTLC in pharmaceutical preparations [103][104][105][106][107][108][109][110][111][112][113][114][115] (table 4). | 7 |
164474492 | Capillary electrophoresis Capillary electrophoresis (CE) is based on charge and size under electric field separate molecules. The capillary tube is made of glass loaded with an electrolyte solution. Electrophoretic mobility is an important parameter for the separation, chemical constituents as well as solvent viscosity. However, the limitation with gel electrophoresis with regards to applied voltage due to ohmic heating damage the gels and restrict the separation. Need to require large voltage often 10-20 thousand for experiments with CE. Different types of capillary electrophoresis are capillary zone electrophoresis (CZE), capillary gel electrophoresis (CGE), micellar electrokinetic capillary chromatography (MEKC), capillary electro chromatography (CEC), capillary isoelectric focusing (CIEF) and capillary isotachophoresis (CITP). Phosphate buffer (pH 6.5) and methanol mixture combined (80:20, v/v) used as background electrolyte with capillary fused silica column under 15 KV voltage at room temperature for the determination amlodipine and atorvastatin [116]. In tablet formulation no interference from present common excipients [117]. Phosphate buffer can separate both drugs in 5 min with high precision but in the presence of acidic products need to involve borate buffer [118][119]. It is likewise possible to quantify within 3 min in combined dosage form with high efficiency and resolution [120]. CZE method validated for solid dosage form in the presence of electrolyte as a methanol borate buffer [121]. MEKC succeeded by controlling surfactant, sodium dodecyl sulfate (SDS) concentration and acquired within 2 min [122] compared to CZE [117] 13 min migration time having comparable resolution. High and ultra-pressure liquid chromatography combined with mass spectrophotometry High pressure and ultra-performance liquid chromatography with the mass spectrometry (LC-MS, UPLC-MS) are analytical techniques that combine liquid chromatography with mass spectrophotometer. The aim to develop a fast and reliable analytical method for the determination of atorvastatin and amlodipine together with the presence of metabolites using the above techniques. The MS combined with LC has high selectivity and sensitivity. The techniques are commonly applied for bioavailability and pharmacokinetics investigation. Mostly quantification of parent drug, active and inactive metabolites are of interest for various studies with biological fluids. It is also required to verify the interaction between drug to drug and side effects as well as the toxicity of different metabolites after metabolism in the human body. The LCMS [123][124][125][126][127][128][129][130][131][132][133][134][135][136] (table 5) and UPLC-MS [137][138][139][140][141][142] (table 6) were used for the determination of amlodipine, atorvastatin and their metabolites in pharmaceutical dosage forms and biological fluids. | 8 |
164474492 | DISCUSSION The UV-visible spectrophotometer does not require any pH adjustment and very close to the pharmacopeia method for both drugs. Recently HPTLC can be applied as an alternative option for traditional TLC method. It is easy to handle with software, which is not possible with TLC. HPTLC enhanced the capability to determine impurity with the help of the hydrophilic phase combined silica gel, an important parameter in all pharmacopoeias. One single run is enough to achieve two parameters such quantity and its impurity by HPLC, main pharmacopeias method to quantify the assay percentage. The setting of parameters for the reaction is not easy as well as for characterization with CE that is why maybe not recommended in official method. UPLC is a high-cost instrument compare with other chromatographic methods, ability to study pharmacokinetics such as adsorption, metabolism. The limit of detection (LOD) and limit of quantitation (LOQ) value is very less with chromatographic method combined with mass spectro-photometry (table 7). Amlodipine and atorvastatin concentration in pharmaceutical formulations and biological fluids are based on different parameters and the calibration curve of the analyte (table 8). During method development and validation, accurately quantified the analyte as well provide brief information related to impurity profiling, a key equipment for the formulation process of the drug. Simple operation procedure, fast, cost effective, accurate in readings and used widely | 9 |
43531704 | In this work, a series of CeO2-SiO2 (30 wt % of ceria)-based catalysts was prepared by the wetness impregnation method and tested for ESR (ethanol steam reforming) at 450–500 ◦C, atmospheric pressure and a water/ethanol ratio increasing from 4 to 6 (the ethanol concentration being fixed to 10 vol %); after every test, coke gasification measurements were performed at the same water partial pressure, and the temperature of the test and the gasified carbon was measured from the areas under the CO and CO2 profiles. Finally, oxidation measurements under a 5% O2/N2 stream made it possible to calculate the total carbon deposited. In an attempt to improve the coke resistance of a Pt-Ni/CeO2-SiO2 catalyst, the effect of support basification by alkali addition (K and Cs), as well as Pt substitution by Rh was investigated. The novel catalysts, especially those containing Rh, displayed a lowering in the carbon formation rate; however, a faster reduction of ethanol conversion with time-on-stream and lessened hydrogen selectivities were recorded. In addition, no significant gain in terms of coke gasification rates was observed. The most active catalyst (Pt-Ni/CeO2-SiO2) was also tested under different operative conditions, in order to study the effect of temperature and water/ethanol ratio on carbon formation and gasification. The increase in the water content resulted in an enhanced reactor-plugging time due to reduced carbonaceous deposits formation; however, no effect of steam concentration on the carbon gasification rate were recorded. On the other hand, the increase in temperature from 450–500 ◦C lowered the coke selectivity by almost one order of magnitude improving, at the same time, the contribution of the gasification reactions. | 1 |
43531704 | Introduction In order to encourage an economy based on clean energy, the demand for hydrogen fuel cells is expected to grow rapidly in the near future [1].Hydrogen is a valid alternative to conventional fuels due to its ability to burn without emitting environmental pollutants, as well as its high energy content per unit of weight (142 KJ/g [2], 2.75 times greater than that of hydrocarbon fuels).Nowadays, methane steam reforming is the most conventional and economical process for hydrogen production [3,4] but other technologies, including biofuels conversion, have been intensively investigated, also due to the bio-feedstock's ability to act as an emission sink within a carbon-balanced life-cycle [5,6].Moreover, among the various renewable sources, biomass is highly promising due to its abundance and low cost [7,8].Biofuels can be produced both from food crops (first generation), as well as the residuals of agricultural and forestry wastes (second generation).Bioethanol presents several advantages, such as a high octane number, high heat of vaporization and, most importantly, reduction of greenhouse gas emissions.In fact, the CO 2 generated during bio-fuels conversion can be recycled for growing plants through photosynthesis, resulting in a carbon neutral process.In addition, bioethanol provides an important route for gasoline replacing, due to its easy handling and hydrogen storage ability [9].Currently, starch and sugar-rich materials are mainly employed for large-scale bioethanol production which, however, are not desirable due to their value as food [10].On the other hand, lignocellulosic biomass is cheap and widely available and can be converted to bioethanol by a pre-treatment-hydrolysis-fermentation cycle [11].Ethanol can be efficiently converted into H 2 by means of its catalytic reaction with steam, according to Equation (1): Despite ethanol steam reforming (ESR) theoretically producing only H 2 and CO 2 , other reactions, such as methanation, water gas shift, dehydration, dehydrogenation, and cracking, can led to the formation of several side products, including methane, carbon monoxide, acetaldehyde, ethylene, acetone, and coke [12,13].For example, unsaturated hydrocarbon (C 2 H 4 ) can be polymerized to coke while the decomposition of saturated hydrocarbons, such as CH 4 , promote carbidic species formation that act as intermediates in the filamentous carbon growth [14].Hence, major challenges of catalyst design for ethanol steam reforming is to maximize hydrogen productivity, inhibiting, at the same time, coke formation.In addition, operating at low-temperatures are highly desired from the point of view of the hydrogen economy and energy consumption [15]. Several metals have been effectively used for the steam reforming of ethanol, due to their capability to break C 2 H 5 OH molecule.In particular, less-oxophilic metals (Pd and Pt) are known to activate α-C-H bonds, while more-oxophilic metals (Co, Ni, Rh, Ru) promote molecule activation via O-H [16].Despite noble metals catalysts being more active and stable than base metal catalysts in ESR reaction, the high costs hinder their practical applications.Conversely, nickel and cobalt-based catalysts are widely used and recognized as appropriate catalysts for ethanol reforming due to their low price and high activity towards C-C bond cleavage [17,18].However, to overcome the considerable coke selectivity observed over these catalysts and to increase the hydrogen yield, the synergistic combination of transition metals with very low amounts of noble metals has been reported as a viable route [19][20][21].It was also shown that adding promoters to Ni-based catalysts is an effective method to prevent carbon deposition.In fact, alkali metals (K, Cs, Na, Li), being electron donators, display excess mobile electrons, which enhances hydrogen spillover on the catalyst surface, thus reducing the amount of coke deposits [22,23].Moreover, due to the neutralization of catalyst acid sites, alkali metals are able to suppress hydrocarbon (CH 4 and ethylene) decomposition and Boudouard reaction.Rass-Hansen et al. [24] found an optimum potassium doping (0.5%) over Ni/MgAl 2 O 4 for maximizing steam adsorption onto the catalyst surface and reduce the carbon formation while Akiyama et al. reported that the cesium-doped Ni/ZrO 2 catalysts improve H 2 yield with respect to Li-and K-based samples and were more effective in decreasing carbon deposition [25]. The nature of the support is also of great importance for the final catalyst performances.It was shown that acidic supports, such as Al 2 O 3 , preferentially promote dehydration while basic support (MgO) favor dehydrogenation reactions.Conversely, reducible supports, including rare earth oxides, display low by-products selectivity and improved hydrogen yield.The superior activity of CeO 2 -based support can be linked to the good metals particles dispersion and the prevention of sintering phenomena; moreover, their capability to add and remove oxygen in a reversible manner facilitates carbon gasification [26].Mobile oxygen of ceria can also activate water, with regard to the formation of hydroxyl groups, resulting in higher ESR efficiency [27].In particular, ceria was shown to accelerate the reaction of steam and absorbed species at the metal-support interface, giving place to -O and -HO species, which are transferred to the surface carbon, thus promoting coke conversion to gaseous products (CO, H 2 , and CO 2 ) [28,29].However, the low intrinsic surface area of reducible supports has encouraged the deposition of thin films of these oxides on porous supports.To that end, silica is a very interesting material due to its high surface area and chemically-inert nature [30].Moreover, the high number of oxygen vacancies in CeO 2 -SiO 2 mixed oxides may increase the lattice oxygen mobility and improve reducibility, activity, and stability of the catalyst [31]. In our previous works [32,33], we demonstrated the efficiency of a bimetallic Pt-Ni catalyst supported on CeO 2 -SiO 2 for hydrogen production via ethanol reforming: the combination of two metals, as well as the choice of a mixed oxide as a support having enhanced redox properties with respect to ceria alone resulted in interesting activity and stability. In this study, a series of CeO 2 -SiO 2 based catalysts were prepared and characterized.The effect of alkali metals (K and Cs) modification, as well as the addition of Rh (or Pt substitution by Rh) on catalyst activity and stability for ethanol steam reforming was investigated.Moreover, once selected the most interesting sample, coke formation and gasification rates were evaluated and compared at different operative conditions (temperature and water/ethanol ratio). | 2 |
43531704 | Catalyst Preparation and Characterization Five CeO 2 -SiO 2 based catalysts (Pt-Ni, Rh-Pt-Ni, Rh-Ni, Pt-Ni-K, Pt-Ni-Cs) were prepared by sequential wetness impregnation.More details about the preparation method are reported in [32].CeO 2 content in the catalyst was previously optimized and fixed to 30 wt %; Ni and noble metals loading (in the bimetallic catalysts) were equal to 10 wt % and 3 wt %, respectively, calculated on the basis of ceria mass.K, Cs, and Rh content in trimetallic catalyst was 0.5 wt % on ceria and potassium hydroxide, caesium chloride (both from Sigma-Aldrich, Saint Louis, MO, USA), and rhodium chloride (Strem Chemicals, Newburyport, MA, USA) were selected as metals salt precursors.K and Cs were directly impregnated on the support, followed by Ni and then Pt while the trimetallic catalysts were prepared by depositing Rh on the Pt-Ni/CeO 2 /SiO 2 sample. The CeO 2 , as well as the metal loading (wt %), were determined by X-ray fluorescence on an ARL (Air Resources Laboratory) QUANT'X ED-XRF (energy-dispersive X-ray diffraction) spectrometer (Thermo Fisher Scientific, Waltham, MA, USA).N 2 adsorption-desorption isotherms at −196 • C were obtained for the determination of the specific surface area (SSA) of the catalytic samples, according to Branauer-Emmet-Teller (BET) method by using a ThermoScientific Surfer (Thermo Fisher Scientific, Waltham, MA, USA).The calcined catalysts, as well as the bare support, were characterized by powder XRD (X-ray diffraction, model D8 Advance Bruker (Bruker, Billerica, MA, USA) using nickel-filtered CuKα radiation over the 2θ range 20-80 • .The Scherrer equation, (d = 0.9•λ•β −1 •cosθ −1 ), where λ is the wavelength of incident radiation (nm), β is the half-height width of the most intense peak for the species (radians) and θ is the Bragg angle ( • ) of that peak, was employed to determine the particle size of the various phases based on their most intense diffraction peaks.The hydrogen temperature programmed reduction (H 2 -TPR) experiments were performed in the laboratory apparatus described in the Section 2.2.The reduction was investigated in the temperature range of 25-500 • C using a constant flow (500 N•cm 3 •min −1 ) of 5% H 2 -N 2 gas mixture.The maximum temperature was held for 1 h in order to assure complete reduction of metals oxides.The H 2 consumption was obtained by integrating the area under the TPR profile. | 3 |
43531704 | Catalyst Testing An amount of the calcined sample (4.5 g) was pressed, sieved into a 45-80 mesh, and loaded in a stainless steel tubular reactor (Officina Elettromeccanica Mormile, Casavatore, Italy) having an annular configuration (internal diameter = 15 mm, external diameter = 17 mm).The sample was treated in an H 2 -N 2 mixture as described above and the catalytic activity was evaluated at atmospheric pressure, 450 • C and water/ethanol molar ratio f.r.(feeding ratio) of 3 (10 vol % of ethanol).Further tests on the Pt-Ni/CeO 2 /SiO 2 sample were carried out at 500 • C and f.r. of 4 and 6.The reaction temperature was measured by means of a thermocouple that was inserted into the tube reactor, in contact with the catalyst bed.A differential pressure sensor (Nagano Sensortechnik, Ottendorf-Okrilla, Germany) allowed monitoring the pressure drop through the catalytic bed.The test was performed until measuring a pressure drop of 500 mbar; then, a N 2 -steam mixture having the same water concentration of the feeding substituted the reacting stream and gasification measurements were carried out.Water/ethanol mixture, stored in a tank under N 2 pressure, was fed into a boiler (T = 200 • C, Officina Elettromeccanica Mormile, Casavatore, Italy) and then into the reactor by means of a mass flow controller for liquids (Bronkhorst High-Tech, Bronkhorst, Ruurlo, The Netherlands) with a flow-rate of 13.4 g•h −1 .N 2 (300 N•cm 3 •min −1 ) was supplied into the boiler as a carrier gas; the resulting weight hourly space velocity (WHSV), defined as the ratio of the ethanol mass flow-rate and catalytic mass, was equal to 4.1 h −1 .The inlet and the outlet lines of the reactor were heated to 160 • C for complete vaporization of the reactant species.The composition of the outlet gas (i.e., CO, CO 2 , CH 4 , H 2 O, and C 2 H 5 OH concentration) was analysed with an on-line FT-IR (Fourier transform-infrared spectroscopy) Spectrophotometer (Antaris IGS Analyser, Thermo Fisher Scientific, Waltham, MA, USA).Unreacted water and ethanol as well as condensable reaction products eventually present were trapped in a condensate collector while the hydrogen concentration in the dry outlet gas was measured with an advanced optima gas analyser from ABB (Caldos 27, Alamo, TX, USA).Ethanol conversion (X), hydrogen yield (Y), carbon formation (CFR), and carbon gasification (CGR) rates were calculated following Equations ( 2)-( 5), respectively, where mass coke,oxidised (in grams) is determined through thermo-gravimetric analysis carried out on the spent catalyst after the reaction + gasification step; mass catalyst (in grams) stands for the catalytic mass; mass carbon,fed (m c,fed in grams) refers to the total mass of carbon fed as ethanol during the test; and time reaction is the time-on-stream in hours.Concerning CGR, the gasification time was set to 60 min (time gasification ) and the mass of carbon oxidized (mass coke,oxidized ) was evaluated by integrating the area under CO and CO 2 signals. | 4 |
43531704 | Ethanol Steam Reforming Tests: Effect of Catalytic Formulation The stability tests carried out at 450 • C and f.r.= 3 were performed for different times, selected in order to reach 500 mbar of pressure drops through the bed and guarantee almost the same mass of carbon deposited.The results shown in Table 3 revealed a very fast reactor plugging for the K-based catalyst, which also displayed a CFR of 0.017 g coke,oxidized •g cat −1 •g c,fed −1 •h −1 .A quite high coke selectivity was also observed over the Pt-Ni sample: pressure drops reached the critical value of 500 mbar within 310 min.However, it is interesting to observe that Rh deposition on Pt-Ni/CeO 2 -SiO 2 catalyst reduced carbon formation rate from 0.0030 to 0.00084 g coke,oxidized On the other hand, over the sample basified by Cs deposition, CFR was halved with respect to the Rh-Pt-Ni sample.The lowest activity towards carbon formation reactions was measured over the bimetallic catalyst containing Rh: also other authors found that Rh is less selective than Pt towards coke precursors formation during reforming [47].However, looking at the coke gasification measurements, differently form the result previously reported about the clear role of alkali metals [48] as well as Rh in carbon gasification reactions [49], CGR was unaffected by catalyst formulation and very similar values were recorded over the five catalysts (Table 3).Figure 3 displays the trend of ethanol conversion as a function of time on stream: TOS (time-on-stream) for all the samples was equal to critical plugging time, except for the Pt-Ni catalyst, which was tested for 5000 min, in order to evaluate in more detail the dependence of X vs TOS.It was found that Pt-Ni and Rh-Pt-Ni catalysts maintained initial catalytic performances for at least 240 min without apparent deactivation.Conversely, similar C 2 H 5 OH profiles were recorded over the Rh-Pt-Ni and Pt-Ni-Cs samples, with an activity reduction from 100% to 97% in the time range of 0-1900 min.The K-containing catalyst displayed the worst performances among the prepared catalysts with a very fast conversion decrease to 93%.The Pt-Ni conversion profile was higher than that recorded over the other samples, with an X value of 95% after 5000 min.It is also interesting to note that the bimetallic catalyst containing Pt also assures an initial hydrogen yield better than the other samples (26.5%) and very close to the value predicted by thermodynamic equilibrium. The unsatisfactory behaviour of the Pt-Ni-K catalyst can be ascribed to its low surface area (Table 1) and a subsequent worse active species dispersion, which reduced ethanol conversion in reforming reactions [50].be ascribed to its low surface area (Table 1) and a subsequent worse active species dispersion, which reduced ethanol conversion in reforming reactions [50].On the other hand, Rh addition had no positive effect on the stability of Pt-Ni catalyst while the bimetallic catalyst containing Rh showed slightly improved activity with respect to the Cs-containing sample.The described results suggest that, despite Rh and alkali metals are able to reduce coke formation rate and, consequently, enhance reactor-plugging time, no improvements can be drawn under the point of view of gasification reactions, which spurs the investigation of other parameters suspected to affect coke removal by steam (water partial pressure and reaction temperature).Moreover, a negative effect of support basification, Rh addition as well as Pt substitution by Rh on the long-term stability and H2 yield of Pt-Ni/CeO2-SiO2 catalyst was observed.Based on the above discussion, the Pt-Ni catalyst was selected as the most interesting sample in terms of catalytic performances and employed for further tests. | 6 |
43531704 | Ethanol Steam Reforming Tests: Effect of Operative Conditions The impact of different amount of steam and the influence of reaction temperatures on the Pt-Ni/CeO2-SiO2 catalyst performances during ethanol steam reforming at WHSV = 4.1 h −1 was also investigated.C2H5OH conversion was not affected by water partial pressure change and 100% of conversion (as predicted by thermodynamic analysis) was measured during all the tests, carried out for a TOS equal to the critical plugging time.A stable product gas distribution was also recorded, with a mean hydrogen yield increasing from 26.5% at f.r.= 3 to 30% and 36%, at f.r.= 4 and 6, respectively; this trend is reasonable since the added steam could favour reforming reactions [51].In addition, a strong variation in the pressure drop profile with the growth of the amount of steam was observed (Figure 4).The plugging time measured during the test at f.r.= 6 was almost eight times On the other hand, Rh addition effect on the stability catalyst while bimetallic containing Rh showed slightly improved activity with respect to the Cs-containing sample.The described results suggest that, despite Rh and alkali metals are able to reduce coke formation rate and, consequently, enhance reactor-plugging time, no improvements can be drawn under the point of view of gasification of other parameters suspected to affect coke removal by steam (water partial pressure and reaction temperature).Moreover, a negative effect of support basification, Rh addition as well as Pt substitution by Rh on the long-term stability and H 2 yield of Pt-Ni/CeO 2 -SiO 2 catalyst was observed.Based on the above discussion, the Pt-Ni catalyst was selected as the most interesting sample in terms of catalytic performances and employed for further tests. | 7 |
43531704 | Ethanol Steam Reforming Tests: Effect of Operative Conditions The impact of different amount of steam and the influence of reaction temperatures on the Pt-Ni/CeO 2 -SiO 2 catalyst performances during ethanol steam reforming at WHSV = 4.1 h −1 was also investigated.C 2 H 5 OH conversion was not affected by water partial pressure change and 100% of conversion (as predicted by thermodynamic analysis) was measured during all the tests, carried out for a TOS equal to the critical plugging time.A stable product gas distribution was also recorded, with a mean hydrogen yield increasing from 26.5% at f.r.= 3 to 30% and 36%, at f.r.= 4 and 6, respectively; this trend is reasonable since the added steam could favour reforming reactions [51].In addition, a strong variation in the pressure drop profile with the growth of the amount of steam was observed (Figure 4).The plugging time measured during the test at f.r.= 6 was almost eight times higher than the value recorded at stoichiometric feeding conditions (Table 4).Moreover, for a water concentration growth in the range 40-60 vol % in the reacting mixture, CFR was reduced of almost one order of magnitude (from 0.0013 to 0.00011 g coke,oxidized •g cat −1 •g c,fed −1 •h −1 ).However, the carbon gasification rate, as it is possible to observe also from the slope of pressure profile during gasification measurements (Figure 4) and from the data shown in Table 4, was not affected by water partial pressure.This phenomenon can be explained considering that, even when the steam to ethanol molar ratio is adjusted to favour the gasification reaction, the kinetics of the reaction can be very slow, resulting in a negligible effect of water partial pressure [52].Based on the above results, the effect of temperature was also studied and the results are shown in Figure 5 and Table 4. Energies 2017, 10, 1030 9 of 13 higher than the value recorded at stoichiometric feeding conditions (Table 4).Moreover, for a water concentration growth in the range 40-60 vol % in the reacting mixture, CFR was reduced of almost one order magnitude (from 0.0013 to 0.00011 gcoke,oxidized•gcat −1 •gc,fed −1 •h −1 ).However, the carbon gasification rate, as it is possible to observe also from the slope of pressure profile during gasification measurements (Figure 4) and from the data shown in Table 4, was not affected by water partial pressure.This phenomenon can be explained considering that, even when the steam to ethanol molar ratio is adjusted to favour the gasification reaction, the kinetics of the reaction can be very slow, resulting in a negligible effect of water partial pressure [52].Based on the above results, the effect of temperature was also studied and the results are shown in Figure 5 and Table 4. higher than the value recorded at stoichiometric feeding conditions (Table 4).Moreover, for a water concentration the range 40-60 vol the reacting CFR one 0.0013 gcoke,oxidized•gcat −1 •h −1 ). is possible to also (Figure the data shown Table 4, was not affected pressure.phenomenon can to gasification reaction, the kinetics of the reaction can be very slow, resulting in a negligible effect of water partial pressure [52].Based on the above results, the effect of temperature was also studied and the results are shown in Figure 5 and Table 4.The trend of pressure drops during stability tests and the carbon formation rate variation with temperature in the range 450-500 • C suggest that the most favourable conditions for carbon deposition are always at the lowest catalyst temperature, where the reactions leading to coke formation are much higher than the rates of carbon gasification reactions [53].The temperature growth from 450 to 500 • C reduced CFR, due to the lower activity towards coke deposits formation and/or the increased contribution of gasification reaction during the test.Moreover, the results of gasification measurements revealed a strong kinetics improvement, which allowed the increase of CGR from 0.035 to 0.25 g •gcat −1 •h −1 . | 8 |
42552672 | Introduction 2][3][4] The reaction of the broad spectrum insecticide fenitrothion, 1, with a variety of oxygen-based nucleophiles has engaged our recent attention. 3,4In aqueous solution, 1 reacts with a variety of oxygen nucleophiles, to include some alpha-nucleophiles and a series of structurally related phenoxides as well as the highly basic nucleophiles OH -and CF 3 CH 2 O -, exclusively at the P center. 3In other words, products of nucleophilic attack at the alkyl and aromatic carbon centers were not detected.Analysis of the kinetic data showed that the thiophosphoryl group transfer proceeds by a concerted mechanism in which bond formation with the incoming nucleophile is slightly ahead of leaving group departure.On the other hand, ethanolysis of 1 by alkali metal alkoxides (M + EtO -, M + = Li + , K + , and Na + ) in anhydrous ethanol proceeds by nucleophilic attack at both P and aliphatic carbon centers; a minor SNAr route was also detected. 4Hence changing the nucleophile/solvent system has clearly introduced additional reaction pathways for 1.An earlier report on the hydrolysis of 1 reveals that CH 3 -O bond fission occurs at low pH while P-OAr fission is the exclusive reaction at high pH. 5To date we have found no report of the reaction of 1. with nitrogen nucleophiles, which is the subject of the present paper.Such a study would be important not only from the point of view of structurereactivity considerations, but also in contributing to the design of possible decontamination strategies for ameliorating the effects of pesticide overload in general.A recent study of phosphoryl transfer from ATP to amine nucleophiles has sought to provide a basis for understanding the analogous enzymatic reactions. 6he pathways available to 1 in its reaction with nucleophiles are shown in Scheme 1.In this paper, we report that 1 reacts with some amine nucleophiles to give mainly products of substitution at P and aromatic carbon centers.An attempt is made to explain site preferences in the reaction of 1 with oxygen and nitrogen nucleophiles by invoking the Hard Soft Acid Base (HSAB) theory and transition state stabilization by hydrogen bonding.The relative nucleophilicities of both nucleophile types towards aromatic carbon and the stability of σcomplex intermediates formed by them in SNAr reactions 7 are additional factors which should also be considered in discussing site preferences by oxygen and nitrogen nucleophiles in their reactions with 1 and similar substrates. | 2 |
42552672 | Results and Discussion Reaction pathways 3-Methyl-4-nitrophenoxide, the product of nucleophilic attack at the P center of 1, absorbs at 398 nm.Quantitative thiophosphoryl group transfer should yield experimental absorbances at the end of the reaction which are identical to the calculated values for this nucleofuge, within experimental error.A definitive check for reactions monitored by conventional uv-visible spectrophotometry would be the measurement of absorbances at the end of the reaction at both high and low pH.Such experiments with n-butylamine, ethanolamine, and glycyl ethyl ester revealed the presence of substituted anilines, in addition to 3-methyl-4-nitrophenoxide. The former are products of attack at the aromatic carbon center of 1. Product analysis of the reaction of n-butylamine with 1 by GC-MS showed unambiguously the presence of N-butyl-3-methyl-4-nitrophenylaniline, a product of nucleophilic attack at the aromatic carbon center.Although the same chromatogram suggested the presence of minor quantities of products of S N 2(C) attack, these were not taken into consideration in the calculations of product distributions given below.For reactions involving ethanolamine and glycyl ethyl ester as nucleophiles, the presence of products of attack at the aromatic carbon center was inferred from spectrophotometric measurements.Values of the pK a of the amines employed in this study are listed in Table 1.The approximate % SNAr product in each case was calculated according to equation (i), where A ∞ and A obs are the theoretical and observed infinity absorbances for the substituted aniline, respectively, on the assumption that the amounts of products formed by nucleophilic attack at the aliphatic carbon are negligible.The dependence of the extent of S N Ar and S N 2(P) products formation on amine concentration is given in Table 2.It is clear that while % S N Ar product increases with amine concentration for n-butylamine and ethanolamine, the amount of S N Ar product remains independent of glycyl ethyl ester concentration.This is a clear indication that the S N Ar reactions of n-butylamine and ethanolamine are base catalyzed while the corresponding reaction of glycyl ethyl ester is not.Plots of % S N Ar product vs. [amine], using the data of Table 2, are linear for both n-butylamine and ethanolamine (not shown). | 3 |
42552672 | Base catalysis and the mechanism of the S N Ar reaction The gross mechanism for S N Ar reactions is given in Scheme 2, in which either the formation of the Meisenheimer-type intermediate, PH, or its decomposition to products could be rate determining.According to this mechanism, the observed second-order rate constant, k A , is related to the microscopic rate constants for the constituent steps through equation (ii). The three nucleophiles investigated in this study are all primary amines; there is therefore Kirby and Jencks, 17 have reported that primary and secondary amines react with pnitrophenyl phosphate dianion in aqueous solutions at both P and aromatic carbon sites; at the latter reaction site, the primary amines investigated did not show any susceptibility to base catalysis while secondary amines participated in reactions which showed varying degrees of response to base catalysis.Such dichotomy in the response of primary and secondary amines to base catalysis in SNAr reactions involving moderately to strongly activated substrates is well documented and the causative factors have also been discussed. 18,25 ernasconi's review 26 provides several examples of SNAr reactions of less activated substrates which are catalyzed by strongly and moderately basic amines, as found in the present study. | 4 |
42552672 | Site preferences in the reaction of 1 with oxygen and nitrogen nucleophiles 8][29][30][31][32][33][34][35][36] Khan and Kirby 37 have published on the multiple structure-reactivity correlations for reactions of phosphate triesters with a variety of nucleophiles.What is clear from the literature is that reactivities are sensitive to substrate structure, nucleophile type and basicity, nature of the leaving group, solvent type and solvation factors, etc. 27-31, 39, 40 Our intention in this section is to keep the substrate constant while examining how change of nucleophile type, from oxygen to nitrogen nucleophiles, influences reaction site preferences especially in alkaline media.In this way, it is hoped that an appreciation of some of the factors that determine site preferences will emerge.It is noted that existing literature comparisons do not incorporate significant information on P=S substrates such as 1, the subject of the present investigation. To summarize, the following are the results so far obtained in the reactions of 1 with oxygen and nitrogen nucleophiles in water and ethanol as solvents.At pH ≤ 7.5, hydrolysis of 1 in aqueous solutions proceeds by way of alkyl-O bond fission; at higher pH (> 9), reaction occurs exclusively by displacement of ArO -through attack at the P center. 5,6In ethanol, the predominant products are those of alkyl-O (ca.43 %) and P-OAr (ca.50%) bond fission; a minor S N Ar pathway, accounting for ca.7% of the reaction products, was observed. 4With a series of structurally related phenoxides as nucleophiles, reaction in water occurs exclusively at the P center. 3Changing the nucleophile to the primary amines used in the present study sets up a competitive process in which attack at the aromatic carbon center is favored to varying extents over the corresponding reaction at P. The behavior of these nucleophiles in alkaline media in their reaction with 1 is amenable to an explanation that is based on the HSAB theory, 41 in which case the "hard" oxygen bases react mainly with the "hard" P center.The fact that "hard" amine nucleophiles, whose basicities are comparable to those of the oxyanions studied previously, show considerable affinity for the aromatic carbon center as well could be attributed to two factors.Firstly, Terrier 42 has shown that amines are intrinsically more reactive than alkoxides of similar basicities towards aromatic carbon centers.This may not be unconnected, in part, with the need to desolvate alkoxide reagents in an activated process which precedes the actual step involving nucleophilic attack.Jencks' results 43,44 demonstrate that amines and thiolates generally tend to be more nucleophilic than oxyanions, essentially as a consequence of the decreased demand for solvation of these nucleophiles as well as the high carbon basicity of thiolates, in comparison to oxyanions.6][47][48] Primary and secondary amine nucleophiles form σcomplexes quite readily, in part because the deprotonation of the first-formed intermediate (see Scheme 2) provides the thermodynamic driving force for the forward reaction, and this effect is lacking when O-based nucleophiles are involved.This factor disfavoring the reaction of O-based nucleophiles should assume greater prominence when the aromatic moiety is much less activated, as in 1.On this score, the observation of SNAr products with amines but not with oxygen nucleophiles can be accounted for. The formation of significant amounts of S N 2(C) products in the ethanolysis of 1 by alkali metal ethoxide in ethanol recently reported by Buncel and co-workers, 4 can be understood if the bulk solvent stabilizes the transition state for alkyl-O bond cleavage through hydrogen bonding to the departing -OP(S)(OCH 3 )OAr anion.These authors showed that free ethoxide is more reactive than either ion paired or dimerized alkali metal ethoxide.Attack by ethoxide at the P center is catalyzed by alkali metal ethoxides.In addition to the products of attack at the P center, which are explicable by the HSAB theory, minor products of ethoxide ion attack at the aromatic carbon center were also observed.The latter products conceivably result from the nucleophilic activity of the significantly more basic EtO -, which promotes attack at the aromatic center in a reaction that is considerably less favored than the processes at the P and alkyl carbon centers.Kirby and Younas 49 have shown that changing oxyanion nucleophiles to more basic ones in the reaction of methyl 2,4-dinitrophenyl phosphate enhances the prospects of SNAr product formation, in addition to attack at the P center. | 5 |
42552672 | Experimental Section General Procedures.Materials.Reagents were commercial products which were either used as received or purified according to literature procedures.Stock solutions of the substrate were prepared under nitrogen and stored in volumetric flasks which were sealed with rubber septa, protected from light by wrapping with aluminum foil and stored in a refrigerator.pH was measured with an Accumet 825 pH meter with a glass electrode calibrated with standard buffer solutions.NMR spectra of the substrate were obtained on a Bruker 400 spectrometer operating at 400 MHz.Product analysis by GC-MS was performed using a Fisons 8000 Gas Chromatography instrument equipped with a MD800 Mass Spectrometer.The GC was equipped with a DB-5 capillary column, and used helium as the carrier gas.The qualitative experiments for the determination of reaction products for processes involving the three amines investigated were performed on a Perkin-Elmer Lambda 5 uv-visible spectrophotometer.Water was distilled, deionized, degassed, and filtered through 0.22 µm filter. O,O-Dimethyl-O-(3-methyl-4-nitrophenyl)phosphorothioate, 1, was a gift from Sumitomo Chemical Co. and was purified by column chromatography; 50 its purity was checked by 1 H and 31 P NMR as well as by GC-MS. | 6 |
42552672 | Determination of reaction products Reaction was initiated by injecting the required amount of a stock solution (9.54 x 10 -3 M) of 1 into a capped glass vial containing the appropriate concentration of the relevant amine at room temperature.In all cases, the amine concentration was in large excess of the substrate.The pH of the reaction mixture was measured.Aliquots of the reaction mixture were then withdrawn, its pH was adjusted to < 5 with dilute HCl and the absorbance measured at 400 nm.At this pH, the absorbances recorded were those due to substituted anilines, i.e. the S N Ar products, since the phenolate products resulting from displacement at the P center would exist in their protonated forms , i.e. the phenols, which would not absorb at pH < 5.The absorbance of the reaction mixture was monitored until no further changes were observed.In all cases, experimental absorbances at "infinite" time were lower than calculated ones, indicating the existence of competing reaction(s).The observed and theoretical infinity absorbances were used to calculate % S N Ar reaction products according to equation (i).The % S N 2(P) products recorded in Table 2 were obtained by difference, on the assumption that the amounts of S N 2(C) products formed by nucleophilic attack at the aliphatic carbon are negligible. structural similarity, in a sense, among them.The results presented above show that while the S N Ar reactions of n-butylamine and ethanolamine proceed by way of rate-determining decomposition of PH (Scheme 2), its formation is rate-limiting for glycyl ethyl ester.With reference to equation (ii), what these results indicate is that for the reactions involving nbutylamine and ethanolamine, the kinetic condition k -1 >> k 2 + k 3 [B] holds, while for the reaction of glycyl ethyl ester the kinetic condition k -1 << k 2 + k 3[B] obtains.The factors determining the incidence of base catalysis or otherwise in SNAr reactions are now well known and have been discussed extensively.[7][8][9][10][11][12][13][14][15][16] | 7 |
52024679 | In this paper a simple, precise and rapid high performance liquid chromatography method with UV detection has been developed for the determination of saxagliptin and metformin in bulk. An Agilent, Zorbax CN (250 × 4.6 mm I.D., 5 µm) column was used with a mobile phase mixture of methanol-50 mM phosphate buffer (pH 2.7) in a gradient elution mode at a flow rate of 1.0 ml min -1 . The analytes were detected at 225 nm and total run time for the method was 7 min. The calibration graphs were linear in the range of 5.00-125.00 µg ml -1 for saxagliptin and 2.50-62.50 µg ml -1 for metformin. For stability indicating study, saxagliptin was subjected to acid, neutral and alkali hydrolysis, oxidation and heat stress. The developed method could be used for quality control assay for SAX in tablets and for stability studies as the method separates SAX from its degradation products and tablet excipients. | 1 |
52024679 | Introduction Saxagliptin (SAX) (1S,3S,5S)-2-[(2S)-2-amino-2-(3-hydroxy-1adamantyl)acetyl]-2 azabicyclo[3.1.0]hexane-3-carbonitrile) ( Figure 1), with C 18 H 25 N 3 O 2 chemical formula and 315.41 g/mol molecular weight, is an orally active, potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-4) for the treatment of Type 2 diabetes, is marketed as Onglyza TM tablet, and also in a fixed dose combination SAX/ metformin (MET) as Kombiglyze TM tablet in USA, Europe and some other countries [1]. DPP-4 inhibitors enhance the body's own ability to control blood glucose by increasing the active levels of incretin hormones in the body. Their mechanism of action is distinct from any existing class of oral glucose-lowering agents. They control elevated blood glucose by triggering pancreatic insulin secretion, suppressing pancreatic glucagon secretion, and signaling the liver to reduce glucose production [2]. In literature two spectrophotometric methods have been reported for the determination of SAX in pharmaceutical preparations [3,4] and three other high performance liquid chromatography (HPLC) methods were developed for analysis of SAX and MET simultaneously [5][6][7][8]. In this study a new stability indicating HPLC method was developed for determination of SAX and MET in bulk drug and validated. The developed method could be used for quality control assay for SAX in tablets and for stability studies as the method separates SAX from its degradation products and tablet excipients. | 2 |
52024679 | Experimental Chemicals Saxagliptin was purchased from Richem International Co., Ltd. (Shanghai, China). Metformin was kindly supplied by Abdi Ibrahim Ilac (Istanbul, Turkey). Commercially available Onglyza ® tablets were purchased from local drug store. Sodium dihydrogen phosphate (NaH 2 PO 4 ), analytical grade ortho-phosphoric acid, HPLC grade acetonitrile and methanol were purchased from Merck (Darmstadt, Germany). Deionized water up to a resistivity of 18.2 MΩ was purified with an Elga water purification system (London, UK). | 3 |
52024679 | Instrumentation and analytical conditions A Shimadzu (Kyoto, Japan) LC 20A liquid chromatograph, consisting of a model LC 20 AT solvent delivery system, a DGU-20A5 degasser and a SIL-20AC auto sampler (set at ambient temperature) and a diode array detector SPD-M20A was used. During method development different wavelengths were scanned with PDA detector in one run and 225nm was found to be the ideal for this study. Data acquisition was performed using LC Solution 1.21 SP1 system software. Separations were performed on an Agilent, Zorbax CN (250 × 4.6 mm I.D., 5 µm) column with an Agilent guard column (4 × 3 mm I.D.) packed with the same material. Chromatographic separation was achieved at room temperature by using methanol-50 mM phosphate buffer (pH 2.7) mixture as mobile phase in gradient elution mode at a (Table 1) was run for 7 min. A typical injection volume was 20 µL. | 4 |
52024679 | Preparation of solutions Stock solutions were prepared by dissolving SAX and MET in acetonitrile and water respectively to give a concentration of 1 mg ml -1 . Standard solutions with a concentration of 100 µg ml -1 were obtained by diluting of the stock solutions with mobile phase mixture (10% methanol, 90% buffer). The final concentrations for SAX and MET solutions were 5.00-125.00 µg ml -1 and 2.50-62.50 µg ml -1 , respectively. The chromatograms were evaluated on the basis of the peak areas of SAX and MET. Buffer solution was prepared by dissolving 6.0 g NaH 2 PO 4 in 1000 mL of water, pH is adjusted to 2.7 by adding orthophosphoric acid drop wise. The prepared solution was filtrated through 45µm filter and sonicated prior to HPLC analysis. | 5 |
52024679 | Acidic, neutral and basic hydrolysis: A solution of SAX 10 mg ml -1 concentration was prepared in acetonitrile, 1 ml of this solution was transferred to three different 10 mL volumetric flasks and diluted up to volume with water, 0.1 HCl and 0.1 NaOH solutions to give a concentration of 1 mg ml -1 . Samples of 0.25 mL were transferred to 5 mL volumetric flask, neutralized and diluted to the volume with mobile phase to a final concentration of 50.00 µg ml -1 . The samples were kept at room temperature and analyzed starting from first hour up to 6 hours. According to the degradation amount, the samples were further subjected to heat 70°C for an hour. Oxidation: A solution of SAX 10 mg ml -1 concentration was prepared in acetonitrile, 1 ml of this solution was transferred to a 10 mL volumetric flask and diluted up to volume with 6 % H 2 O 2 . The prepared solution was kept at room temperature and was analyzed as the hydrolysis samples. Thermal degradation: Bulk drug of SAX was exposed to 50°C dry heat for 1 h, 70°C for 1 h and 105°C for 6 hours. | 7 |
52024679 | Validation of the method The methods were validated according to the ICH guidelines. The calibration curves were obtained between the concentrations of 5.00-125.00 µg ml -1 and 2.50-62.50 µg ml -1 , for SAX and MET respectively. The solutions were prepared in triplicate. Linear regression equations (intercepts and slopes) for mixtures of SAX and MET were established and calculated by the least square regression method. Precision of the analytical method was tested by analyzing six replicate determinations of three different concentrations (high, medium and low) of SAX and MET both on within-day and day-to-day. The accuracy was determined by recovery test using standard addition method. This experiment was performed at three different concentration levels, in which sample stock solutions (25.00 µg ml -1 and 12.50 µg ml -1 for SAX and MET, respectively) were spiked with standard drug solutions of 25.00, 50.00 and 75.00 µg ml -1 for SAX and 12.50, 25.00 and 37.50 µg ml -1 for MET. The mixtures were then analyzed by the proposed methods. Five replicate samples of each concentration level were prepared. The recovery tests were performed using tablet solution containing various amounts of SAX and MET. Sensitivity of the method was decided by determination of limit of detection (LOD) and limit of quantification (LOQ). LOD is the lowest detectable concentration of the analytes by the method while LOQ is the minimum quantifiable concentration. LOD and LOQ were calculated by using the values of slopes and intercepts of the calibration curves for both of the drugs. | 8 |
52024679 | Assay for the tablets Onglyza tablet which contains 5 mg saxagliptin was used for the tablet assay. Ten tablets were separately weighed and finely powdered. About 25 ml of methanol and 50 mL of buffer solution was added to accurately weighed amount of the powder equivalent to the median mass of one tablet in a 100 ml calibrated flask. The mixture was shaken mechanically and sonicated in ultrasonic bath totally 30 min and diluted to volume with buffer solution and then filtered. The filtrate was diluted with the mobile phase (90% buffer: 10% methanol) to give a final concentration of 20.00 µg ml -1 of SAX and analysed with HPLC. The quantity of the SAX was calculated from the regression equation constructed for the SAX assay. | 9 |
52024679 | Method development and optimization To optimize the chromatographic conditions a reversed phase cyano HPLC column and a phosphate buffer at a pH of 2.7 and methanol mixture were found to be the best stationary phases and mobile phase combinations to have two symmetrical and well-resolved peaks for SAX and MET. An optimized gradient program provided sufficient selectivity in a short separation time. The total runtime for the analysis is 7 min and the retention time for MET and SAX 3.47 and 5.83 min, respectively. Blank chromatogram overlapped with mixture of SAX and MET was presented in Figure 2 and single chromatograms of SAX and MET could be found in Figures 3-5, respectively. The system suitability parameters were found to be within the suitable range Rs (resolution) > 15 between two peaks (range Rs ≥ 2); T (peak tailing factor) 1.21 | 10 |
52024679 | Stress testing SAX was forced to degradation acid and alkali hydrolysis. The rate of acid hydrolysis was slower as compared to that alkali. Acid hydrolysis has almost no degradation product but just decreases in amount. The solution was stable up to 6 hours at room temperature, after this the solution was subjected to heat of 70°C for an hour and 17.03% of the solution was decomposed ( Figure 5). In alkali hydrolysis there was degradation product in the beginning and the drug was decomposed of 14.36 % (Figure 6). The solution was stable in water first two hours but it was decomposed up to 15.41% without any degradation by-product (Figure 7). As per the oxidative hydrolysis the drug was decomposed immediately 24.75%, degradation products were shown in Figure 8. The drug powder was exposed to 50°C for 1 h and found to be stable, the temperature was increased to 70°C and the drug is degraded 16.23% in 1 h. SAX exposed to the heat for 6 hours at 105°C and the bulk drug substance was melted completely and decomposed at the end of this treatment. The percent amount of drug degraded after degradation studies are given in Table 2. The results obtained from the stress testing showed that SAX is unstable under hydrolysis, oxidation and thermal stress. Therefore, care should be taken in the manufacturing process and during the storage of the product and the developed method could be used for stability studies of SAX. | 11 |
52024679 | Validation of the method The equations of the calibration curves were y= 14859x+103450, r 2 =0.9976 and y=69798x-70654, r 2 =0.994 for SAX and MET, respectively. The result shows a good correlation existed between peak area and concentration of each drug within the concentration range tested. The analytic and chromatographic data for the developed methods were given in Table 3. The precision of the methods were assessed by carrying out six replicate determinations of three different concentrations of SAX and MET both on within-day and day-to-day (Table 4). RSD values were less than 1.07 and 1.52% indicating good precision and there was no significant difference between the assays tested on the same day or different days. The accuracy of the developed method was determined by the standard addition technique which was done by adding three different concentrations of the standard drug solution to the tablet solution. The results obtained from the standard addition method were given in Table 5. LOD and LOQ were calculated as 3σ/S and 10σ/S, respectively, where S is the slope of the calibration curve and σ is the standard deviation of y-intercept of regression equation [11]. | 12 |
233655254 | : Skin is being increasingly exposed to artificial blue light due to the extensive use of elec ‐ tronic devices, which can induce cell oxidative stress, causing signs of early photo aging. The Melissa officinalis phytocomplex is a new standardized cosmetic ingredient obtained by an in vitro plant cell culture with a high content of rosmarinic acid. In this study, we examine the activity of the Melissa officinalis phytocomplex to protect skin against blue light and infrared damages, evaluating the ROS (Radical Oxygen Species) level in keratinocyte cell line from human skin (HaCaT) and Nrf2 (Nuclear factor erythroid 2 ‐ related factor 2), elastin, and MMP1 (Matrix Metalloproteinase 1) immunostain ‐ ing in living human skin explants ex vivo. This phytocomplex demonstrates antioxidant activity by reducing ROS production and thus the oxidant damage of the skin caused by UV and blue light exposure. In addition, it inhibits blue light ‐ induced Nrf2 transcriptional activity, IR ‐ induced elastin alteration, and IR ‐ induced MMP ‐ 1 release. This Melissa officinalis phytocomplex is a new innovative active ingredient for cosmetic products that is able to protect skin against light and screen exposure damages and oxidative stress. ROS were detected by diacetylated 2 ,7 ′‐ dichlorofluorescein (DCF ‐ DA) staining at basal condition and following the exposure to oxidative stimulus H 2 O 2 . The fluorescence was measured by using a Victor3X multilabel plate counter (Ex 485 nm and Em 535 nm). Results are expressed as fold change of ROS production compared to control. Each bar the mean SD of n=3 experi ‐ ments. $$$ | 1 |
233655254 | Introduction Melissa officinalis L. (lemon balm) is an edible perennial herb of the Lamiaceae family. Its name originates from the Greek words for bee (melissa) and honey (meli). There are worldwide records of its medicinal and culinary use that date back to Dioscorides (father of pharmacology) times (40-90 A.D.) and allow its safe exploitation [1]. Melissa officinalis is reputed in folk medicine for memory-enhancing effects, promoting long life, action against gastrointestinal disorders, rheumatism, Alzheimer's, thyroid diseases, colic, anemia, nausea, vertigo, syncope, asthma, bronchitis, amenorrhea, cardiac disorders, epilepsy, insomnia, migraines, nervousness, malaise, depression, psychosis, hysteria, and wounds [2]. Several scientific papers confirm the medicinal effectiveness of Melissa officinalis preparations, as well as its antioxidant and other properties suggesting its use for the prevention of oxidative stress-related diseases [3]. The bioactivity of Melissa officinalis extracts is mainly attributed, as for any other plant formulation, to the qualitative and quantitative composition of secondary metabolites (i.e., phenolic acids, flavonoids, and terpenoids). Rosmarinic acid is a caffeic acid ester with 3,4-dihydroxyphenyllactic acid, and it is a main bioactive component of the Melissa officinalis extracts [1]. The rosmarinic acid and phenolic acids content in the Melissa officinalis extract is highly variable. The variability is associated with multiple factors, which are difficult to control: seasons, plant age, geographical growing areas, and tissues used for the preparation of products [4]. Furthermore, the preparation of standardized Melissa officinalis derivatives with a reproducible content of metabolites is very difficult. The extreme variability in the content of phytoconstituents of plant preparations obtained directly from a plant, or parts thereof, by extraction negatively impacts the effectiveness of the same. An alternative method for obtaining contaminant-free standardized plant preparation in industrial quantities is to use in vitro cell cultures. Plant cell culture technology is a technique for growing plant cells under strictly controlled environmental conditions [5] that makes it possible to solve the problems tied to the variability of plant extracts, since it provides preparations with a content of active substances that can be reproduced in a standardized manner. The derived extracts can be easily standardized in their primary and secondary metabolites and are compliant with the safety requirements of being contamination-free and phytochemically uniform [6]. In addition, to respect biodiversity and greater environmental sustainability with a drastic reduction in the use of natural resources such as water and soil, this technology makes it possible to overcome seasonal and geographical limitations by guaranteeing a higher safety profile for the consumer (free from heavy metals, pesticides, aflatoxins, bacterial or fungal contamination) and an elevated degree of standardization. The objective of the present study concerns the appraisal of the biological activity of a product rich in rosmarinic acid obtained by a stable and selected cell line of Melissa officinalis [7]. In this work, we demonstrate the efficacy of a Melissa officinalis product obtained by in vitro cell cultures to protect the skin against blue light and IR damages. The skin is the main defensive barrier in the body against a large variety of environmental factors and is responsible for maintaining body homeostasis, defence, and repair [8]. It is well known that exposure to internal and external factors activates lots of molecular processes that damage skin structure. The sunlight spectrum consists of short, highenergy wavelengths, from ultraviolet radiation (280-400 nm) to visible light (400-700 nm) and infrared radiation (700 nm-1 mm), long and low energy wavelengths [9]. Visible light wavelengths penetrate the deepest parts of the dermis, reaching the different types of skin cells and inducing cell oxidative stress, damage, and dysfunction, causing signs of early photo-aging [10]. Skin is being increasingly exposed to artificial blue light due to the extensive use of electronic devices. This, together with recent observations reporting that blue light can exert cytotoxic effects associated with oxidative stress and promote hyperpigmentation, has sparked interest in blue light and its potential harmful effects on skin [11]. Several studies report that blue light contributes to skin aging and carcinogenesis, mostly during direct sunlight exposure, similar to UVA [12]. Numerous pharmacological activities of rosmarinic acid have been described. Among other activities, it protects cells membranes against oxidative damage [13]. Fernando et al. [14] showed that rosmarinic acid treatment of keratinocyte cell line from human skin (HaCaT) cells damaged from UVB radiation recovered the expression levels of Nrf2 (Nuclear factor erythroid 2-related factor 2) protein from the cytosol into the nucleus. These results indicate that rosmarinic acid may protect cellular environments from freeradical damage and thereby enhance the cellular antioxidant defense system. In this work, we examine the efficacy of an ingredient highly standardized in rosmarinic acid that was obtained by a selected cell line of Melissa officinalis, to protect the skin against blue light and IR damages. Especially, we demonstrated the activity of this new ingredient in countering the harmful action of ROS (Radical Oxygen Species), in inhibiting the expression of Nrf2 and MMP1 (Matrix Metalloproteinase 1), and in protecting the degradation of elastin. The evaluation of these parameters has allowed us to ascertain that the Melissa officinalis phytocomplex obtained by in vitro cell culture, standardized in rosmarinic acid, is able to reduce skin damages caused by ROS, blue light, and IR exposure. | 2 |
233655254 | Melissa officinalis Cell Culture Cell culture of Melissa officinalis L. was obtained from seeds bought and certified from the nursery plant "Le Georgiche", Brescia, Italy. The sterile plants of Melissa officinalis L. were obtained from seed sanitized by means of a treatment in sequence with 70% (v/v) ethanol (Honeywell, Wunstorfer Straβe 40, D-30926 Seelze, Germany)) in water for about 2 minutes, 2% (v/v) of sodium hypochlorite solution (6-14% active chlorine, (MERCK KGaA, 64271 Darmstadt, Germany) and 0.1% (v/v) Tween 20 (Duchefa, Postbus 809, 2003 RV-Haarlem, The Netherlands) for 15 minutes and, finally, at least 4 washes with sterile distilled water. The sanitized seeds were placed in trays containing nutrient medium Gamborg B5 [15] rendered solid by adding 0.8% w/v of plant agar (Duchefa) and without growth hormones. After a suitable period of incubation under light (15 days) and at 25 °C, the seeds began to sprout. Twenty days after germination, small leaves were collected from the plants grown under sterile conditions. The leaves were fragmented into small pieces (explants) of sub-centimetric dimensions (0.1-0.5 cm). The fragments of plant tissue were deposited in Petri dishes containing solidified Gamborg B5 medium supplemented with 20 g/L sucrose (Sudzucker AG, Manheim, Germany), 1 mg/L of (NAA) naphtalenacetic acid (Duchefa), 1 mg/L of (IAA) indoleacetic acid (Duchefa), 0.5 mg/L of (K) Kinetin (Duchefa), and 0.9% (w/v) of plant agar, final pH 6.5 (MO Medium). The pH was adjusted to 6.5 before autoclaving. Explants were incubated at 25°C in the dark. Calli grown on Melissa officinalis phytocomplex (MO) medium were subjected to subculture for at least 4 months until they became friable and homogeneous, with a constant growth rate (Melissa officinalis stable cell line). The botanical origin of Melissa officinalis L. was confirmed by fingerprint DNA analysis made from Parco Tecnologico Padano, Lodi, Italy [16]. A part of selected calli (10% w/v) was transferred into 250 ml of culture liquid medium (MO medium without Plant Agar) contained in Erlenmeyer flasks of 1 liter volume. The suspension cultures were maintained at 25 °C in the dark in constant agitation on the rotary shaker at 120 rpm, and every 7 days of fermentation, they were subjected to a liquid subculture. The volume of biomass was increased by subculture on flasks of 3l volume containing 1l of fresh liquid medium culture. The amount of suspension culture inoculated into the liquid medium was equal to 6% v/v. To increase the content of rosmarinic acid, after 7 days of fermentation, the suspension culture was inoculated in a bioreactor of 5L volume containing 3L of MO final liquid medium (Gamborg B5 with the addition of 35 g/L of sucrose, 0.5 mg/L di NAA, 0.5 mg/L of IAA, and 0.25 mg/L of K, final pH 6.5). The suspension culture was grown for a culture cycle of 14 days. | 3 |
233655254 | Phytocomplex Preparation from Melissa officinalis Cell Culture After 14 days of growth, at 25 °C and in the dark, the Melissa officinalis cell suspensions were filtered by 50 μm mesh filter, and the medium cultures were discarded. Cells were washed with a double volume of saline solution (0.9% w/v NaCl in sterile water) and added with 1% (w/w) of citric acid and then homogenized with ultraturrax at 15,000 rpm for 20 minutes. The biomass of homogenated cells was dried to obtain a powder of phytocomplex with a high content of rosmarinic acid. | 4 |
233655254 | Quantification of Rosmarinic Acid and the Total Polyphenols in the Melissa officinalis Phytocomplex by UPLC-DAD First, 100 mg of powder of the Melissa officinalis phytocomplex were weighed into a 15 ml test tube, and 30 volumes of ethanol (Honeywell) and water 60:40 (v/v) were added. The suspension was mixed for 30 seconds with a vortex mixer and sonicated for 15 minutes in an ice bath; finally, it was centrifuged at 4000 rpm for 15 minutes at 6 °C. At the end of centrifugation, the supernatant was recovered. Then, 15 mL of supernatant were transferred into a new test tube 15 and preserved in ice until loading into the UPLC system. The sample was diluted 1:10 (first 1:5 in a solvent and then 1:2 in water). The diluted sample was filtered over 0.22 μm filters before being loaded into the UPLC system. Five independent replicates of the phytocomplex were extracted and measured. The chromatography system used for the quantification of rosmarinic acid consists of an Acquity UPLC BEH C18 1.7 μm column, size 2.1 mm × 100 mm, coupled to an Acquity UPLC BEH C18 1.7 μm VanGuard Pre-Column 3/Pk, size 2.1 mm × 5 mm. The platform used for the UPLC-DAD (Ultra Performance Liquid Chromatography-Diode Array Detection) analysis comprises a UPLC system (Waters Corporation, Milford, MA 01757, USA) consisting of an eluent management module, Binary Solvent Manager model I Class, and an autosampler, Sample Manager-FTN model I Class, coupled to a PDA (Photo Diode Array) eλ diode array detector. Empower 3 (Waters) software was used to acquire and analyze the data. The chromatography method used was the following: solvent A: water, 0.1% formic acid; solvent B: 100% acetonitrile. The initial condition is 99% solvent A; moreover, the flow remains constant at 0.350 mL/min throughout the duration of the analysis. The chromatography column was temperature controlled at 30 °C. Elution of the molecules was conducted by alternating gradient and isocratic phases, as indicated in Table 1. For quantification of the rosmarinic acid, the chromatogram obtained at the wavelength of 330 nm was used. The rosmarinic acid was quantified thanks to the calibration curve of the authentic commercial standard of rosmarinic acid (CAS 20283-92-5; pu-rity≥95%; Sigma Aldrich). The data analysis was carried out with Empower 3 software. HaCaT cells (5 × 10 3 ) were seeded into 96-well plates, allowed to adhere overnight, and then treated for 24 hours with the compounds, according to the experimental protocol. ROS levels were measured after the addition of 100 μM DCF-DA, further incubation for 30 min at 37 °C, and wash with phosphate-buffered saline (PBS) [17] as previously described. N-acetyl-L-cysteine 5 mM (Sigma Aldrich) and Rutin at 0.1% w/v were used as positive controls and the Melissa officinalis phytocomplex was used at 0.1% w/v. Probe fluorescence intensity was measured at excitation 485 nm-emission 535 nm, in the absence or presence of 1.1 μM H2O2 used as oxidative stimulus, using a Multilabel Plate Reader VICTOR X3 (PerkinElmer). Fold increases in ROS production were calculated using the equation: where F is the fluorescence reading. The statistical analysis was performed using GraphPad Prism version 6 for Windows (GraphPad Software, San Diego, CA, USA). Results are presented as mean ± SD of 3 experiments. An unpaired Studentʹs t-test was used to compare ROS values, and p values <0.05 were considered statistically significant. | 5 |
233655254 | Sample Preparation and Explant Distribution Human living skin explants were prepared from an abdominoplasty (aesthetic surgery) from a 35-year-old healthy Caucasian woman with a phototype II-III (Fitzpatrick classification), after obtaining informed consent. Adipose tissue was removed, and explants of 1 cm² were prepared using a circular biopsy punch. The explants were maintained in survival cell culture conditions at 37° C in a humid atmosphere enriched with 5% CO2 in BIO-EC's explant medium. BIOEC's explant medium is a proprietary culture medium specifically engineered by the BIO-EC Laboratory for the survival of skin explants. | 6 |
233655254 | Product Preparation and Application The Melissa officinalis phytocomplex (MO) has been prepared in sterile distilled water at 0.05% and 0.1% (w/v). Successively, the MO at 0.05% and MO at 0.1% were applied topically based on 2 mg/cm² and spread using a small spatula on day 0 (D0), day 1, day 4, and day 5 (30 min before blue light or infrared exposure). The control explants "C" did not receive any treatment. | 7 |
233655254 | Blue Light Irradiations Skin explants from the batches "BL", "MO at 0.05% + BL", and "MO at 0.1% + BL" were exposed to blue light using the Solarbox® device (SATIE, France), which is a visible light radiation system, designed and produced by the SATIE laboratory (CNRS joint research unit UMR 8029, Cergy Paris University). The light source is ensured by a set of configurable light-emitting diodes able to deliver visible blue radiation with an emission spectrum of 420 to 580 nm, with a peak at 455 nm. On day 5, the explants of the batches mentioned above were exposed to a blue light dose of 63.75 J/cm 2 . The unirradiated explants were kept in the dark during the whole time of blue light exposure. | 8 |
233655254 | Infrared Irradiation Skin explants from the batches "IR", "MO at 0.05% + IR", and "MO at 0.1% + IR" were irradiated using an infrared lamp (Dr FISCHER 1000W, 235V 2500K; 760-1150 nm) on day 5, with an infrared dose of 720 J/cm 2 . The unirradiated explants were kept in the dark during the whole time of infrared exposure. | 9 |
233655254 | Histological Processing On day 6 (D6), 24 hours after blue light or infrared exposure, the explants from each batch were collected and cut in two parts. Half was fixed in buffered formalin, and the other half was frozen at -80°C. After fixation in buffered formalin, the samples were dehydrated and impregnated in paraffin using a Leica PEARL dehydration automat. The samples were embedded using a Leica EG 1160 embedding station. Then, 5-μm-thick sections were made using a Leica RM 2125 Minot-type microtome, and the sections were mounted on Superfrost® (Menzel-Gläser, Hungary) histological glass slides. | 10 |
233655254 | Staining and Immunostaining The cell viability of epidermal and dermal structures was observed on formol-fixed paraffine-embedded (FFPE) skin sections after Masson's trichrome staining, Goldner variant. The cellular viability was assessed by microscopical observation. Both immunohistochemistry and immunofluorescence stainings were performed on either 5μm-thick FFPE skin sections or 7μm-thick frozen sections using the following primary antibody: anti- The microscopical observations were realized using an Olympus BX63 microscope. Pictures were digitized with a numeric DP74 Olympus camera with cellSens Dimension storing software (Olympus, Tokyo, Japan). The intensity level of each immunostaining was scored from 1 to 6. | 11 |
233655254 | Melissa officinalis Phytocomplex With High Content of Rosmarinic Acid Was Obtained by a Stable and Selected Cell Line A stable and selected cell line of Melissa officinalis was obtained using the MO solid medium. In this selected solid medium, the Melissa officinalis cell line is beige-colored with brown tinges and has a friable texture and a high rate of growth (subculture in fresh solid medium every 14 days). Figure 1 shows the cell culture maintained in solid MO medium (a) and cells of the line Mo-4AR seen under an AXIO-Imager A2 optical microscope (ZEISS), in the bright field mode (b) and after staining with fluorescein diacetate (c). The content of rosmarinic acid and total polyphenols in the cell line was optimized using a MO final liquid culture medium with a higher content of sucrose (35g/L) and with a lower concentration of growth hormones (0.5 mg/L of NAA, 0.5 mg/l of IAA, and 0.25 mg/L of K). The cells grown into MO final liquid culture medium were used to prepare the Melissa officinalis phytocomplex. The UPLC-DAD analysis was used to estimate the content of rosmarinic acid and total polyphenols content into the Melissa officinalis phytocomplex. The chromatographic profile of the phytocomplex at 330 nm is shown in Figure 2. The data obtained show that the content of rosmarinic acid in the phytocomplex is 7.6 ± 0.1% w/w and the content of total polyphenols expressed as equivalent in rosmarinic acid is 9.2 ± 0.1% w/w. Thus, the main component of total polyphenols in the phytocomplex is represented by rosmarinic acid (83% of the total polyphenols). | 13 |
233655254 | Melissa officinalis Phytocomplex Exhibits Strong Inhibition of ROS Production after H2O2 Oxidative Stimulus in HaCaT Cell Line In order to evaluate the ability of the Melissa officinalis phytocomplex to modulate the oxidative stress, ROS levels in HaCaT cells were evaluated, following 24 hours' treatment. ROS generation was evaluated both in basal conditions and following the oxidative stimulus, which was induced by the addition of H2O2. The obtained results showed a significant decrease in ROS production in HaCaT cells treated with the Melissa officinalis phytocomplex, in the presence of oxidative stimulus, able to increase ROS levels, as shown in the untreated cells ( Figure 3). The positive antioxidant controls, NAC 5 mM and Rutin 0.1% w/v, confirmed the anti-oxidant effect of the Melissa officinalis phytocomplex. ROS were detected by diacetylated 2′,7′-dichlorofluorescein (DCF-DA) staining at basal condition and following the exposure to oxidative stimulus H2O2. The fluorescence was measured by using a Victor3X multilabel plate counter (Ex 485 nm and Em 535 nm). Results are expressed as fold change of ROS production compared to control. Each bar represents the mean ± SD of n=3 experiments. *p < 0.05, **p < 0.01, ***p < 0.001, treatment vs. basal control. $$$ p<0 .001, treatment vs. stimulated control. | 14 |
233655254 | Cell Viability The application of the Melissa officinalis phytocomplex at 0.05% w/v and at 0.1% w/v on human skin explants induces no modification on the cell viability compared to the untreated control on D6, demonstrating that the product is well tolerated by ex vivo human skin. Neither the blue light nor infrared irradiation induces modification of the cell viability. Upon irradiations, the application of the Melissa officinalis phytocomplex at 0.05% and at 0.1% w/v induces no modification of the cell viability to the batches (Figure 4). | 15 |
233655254 | Nrf2 Immunostaining The results of the immunostaining using the antibody anti-phosphorylated Nrf2 in the living epidermidis are summarized in Figure 5. After 6 days of treatment, the Melissa officinalis phytocomplex 0.05% (P1) or 0.1% w/v (P2) does not modify the basal level of Nrf2, compared to the untreated control batch. Figure 5. Scoring of the Nrf2 immunostaining by microscopical examination on D6, on unexposed or blue light-exposed batches (BL). T is the untreated control, P1 and P2 are the batches treated with the Melissa officinalis phytocomplex at 0.05% and 0.1%, respectively. The blue light irradiation induces a moderate increase of the activated (nuclear) form of Nrf2 in the living epidermis. The Melissa officinalis phytocomplex application at 0.05% w/v induces a slight decrease of the activated form of Nrf2 activation upon blue light exposure, so it partially reduces blue light-induced Nrf2 increase. In parallel, the phytocomplex application at 0.1% w/v completely inhibits the blue light-induced Nrf2 increase (Figure 6). | 16 |
233655254 | MMP-1 Immunostaining The results of the staining of MMP-1 in the papillary dermis on all the batches are summarized in Figure 9. After 6 days of treatment, the Melissa officinalis phytocomplex 0.05% w/v induces a slight increase of MMP-1 level, whereas when applied at 0.1% w/v, the phytocomplex induces a slight decrease of MMP-1 level compared to the untreated control batch. Figure 9. Scoring of the MMP-1 (Matrix Metalloproteinase 1) immunostaining by microscopical examination on day 6 on unexposed or infrared exposed batches (IR). T is the untreated control, P1 and P2 are the batches treated with the Melissa officinalis phytocomplex at 0.05% and 0.1% respectively. Upon IR irradiation, the Melissa officinalis phytocomplex at 0.05% w/v induces no variation of MMP-1 level in the papillary dermis. On the contrary, the phytocomplex at 0.1% w/v induces a fairly clear decrease, so it totally prevents IR-induced MMP-1 increase in the dermis (Figure 10). | 18 |
233655254 | Discussion The Melissa officinalis phytocomplex with a high and a standardized content of rosmarinic acid (7.6 ± 0.1% w/w) was obtained by using a plant cell culture technology [7]. Traditional plant extracts have extreme variability in the phytocomplex composition, and it depends on a lot of factors such as climate, soil, and cultivation techniques. This variability cannot guarantee the efficacy of the extract in health care applications. Using in vitro cell culture technology, we can obtain standardized products free from pesticides, contaminates, and residual solvents, maintaining similar biological efficacy in all batches [6]. The Melissa officinalis phytocomplex is standardized in the rosmarinic acid and total polyphenols content, which confers highly reproducible biological activities. The use of the plant secondary metabolite rosmarinic acid has been studied in pharmaceutical and dietary supplements in Alzheimer's disease, atopic dermatitis, and cardiovascular disease [18,19]. Previous research has revealed that the effects of rosmarinic acid in these contexts are mediated by its antioxidant properties [20]. In the present work, we demonstrate the antioxidant properties of the Melissa officinalis phytocomplex using a stress oxidative model in the human cell line HaCaT after stimulus with H2O2. Keratinocytes represent 95% of the epidermal cells. Primarily, they play the structural and barrier function of the epidermis, but their role in the initiation and perpetuation of skin inflammatory and immunological responses, and wound repair, is also well recognized. The spontaneously immortalized human cell line HaCaT exhibits normal morphogenesis and expresses all the major surface markers and functional activities of isolated keratinocytes; for this reason, HaCaT will be chosen as a model for the study of keratinocytes functions and for investigating the effects of the compounds of interest on an epidermal model. Lorrio et al. demonstrated that a natural aqueous extract of Deschampsia antarctica protects skin against artificial ad natural light by reducing the production of ROS and hyperpigmentation in fibroblasts and melanocytes [11]. In this study, the chemical composition of the natural aqueous extract of Deschampsia antarctica was not described, while in our work, we obtained a phytocomplex highly strandardized in polyphenol content using the cell culture technology. The standardization in marker metabolites of the final product is a key point to guarantee the antioxidant efficacy of the Melissa officinalis phytocomplex. Skin is the essential barrier protecting organisms against environmental insults and minimizing water loss from the body. Skin aging and dysfunctions are determined by several factors, including internal metabolism and environmental toxicant exposure. One of the leading causes of these processes is oxidative stress. Although there are efficient antioxidant systems in skin, the excessive and uncontrolled production of ROS is a major pathogenic factor that causes a range of skin diseases, inflammations, allergic reactions, and also neoplastic processes. To assess the ability of the Melissa officinalis phytocomplex to modulate the oxidative stresses, the general ROS levels in HaCaT cells were evaluated using a chemical fluorescent probe. The results obtained show that among a significant increase in ROS levels induced by oxidative stimulation, 0.1% w/w of the Melissa officinalis phytocomplex is able to prevent ROS formation, showing a potent antioxidant effect. The effect of the Melissa officinalis phytocomplex is comparable to the one observed for the pure compound Rutin (0.1% w/w) and is stronger than NAC (N-Acetyl-L-Cysteine) at 5 mM. This result indicates a potential protective effect of the Melissa Officinalis phytocomplex against ROS-mediated cell impairments. Probably, the Melissa officinalis phytocomplex with a high content of rosmarinic acid (7.6% w/w) rescued H2O2-mediated inhibition of Nrf2 transcriptional activity and the consequential decrease in Nrf2 target gene expression [20]. Consistent with these findings, a previous study demonstrated that rosmarinic acid inhibits UVB-induced ROS production and the decrease in protein levels encoded by Nrf2 target genes in HaCaT keratinocytes [14]. Nrf2 is a key transcription factor in the cellular response to oxidative stress. Human Nrf2 has a predicted molecular mass of 66 kDa, and it is ubiquitously expressed in a wide range of tissues and cell types. Under oxidative stresses, including UV irradiation, Nrf2 is activated by phosphorylation and translocates from the cytoplasm to the nucleus. So far, different cytosolic kinase, including protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), andER-localizedpancreatic endoplasmic reticulum kinase (PERK) have been shown to modify Nrf2 and are potentially involved in the dissociation of Nrf2 from its inhibitor, Keap1 [21]. Once in the nucleus, Nrf2 binds to the DNA at the location of the Antioxidant Response Element (ARE) or also called hARE (Human Antioxidant Response Element), which is the master regulator of the total antioxidant system. Nrf2 plays a role in protecting human skin keratinocytes from UVA radiation-induced damage [22] and environmental pollution [23]. The protection effect of the Melissa officinalis phytocomplex against the irradiation of blue light was evaluated on living human skin explants ex vivo by the immunostaining of Nrf2. As shown in Figure 6, the blue light irradiation induces an increase of nuclear translocation of Nrf2 in the living epidermis. The Melissa officinalis phytocomplex at 0.05% w/w presents a fairly good protection activity against blue light irradiations by partially reducing the Nrf2 blue light-induced activation. The higher concentration (0.1% w/w) of the phytocomplex presents a good protection activity against blue light irradiations by totally reducing the Nrf2 blue light-induced activation, suggesting that the Melissa officinalis phytocomplex is able to maintain a healthy balance of anti-oxidant response upon blue light irradiation. The protection effect of the Melissa officinalis phytocomplex against the irradiation of infrared was evaluated on living human skin explants ex vivo by immunostaining of elastin and MMP-1. Elastin is a protein of the connective tissue responsible for the elastic properties of the skin. It is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues, and it is localized mainly on the elastic fibers of the papillary dermis [24]. The principal function of elastin is its ability to elastically extend and contract in repetitive motion when hydrated. Elastin is the major component (90%) of the elastic fibers of the skin. Several factors including the formation of methylglyoxal [25] or UV exposure are able to damage the elastic network of dermis, including elastin [26]. In dermo-cosmetic research, elastin is usually used as a bio-marker of the structural state of the extracellular matrix of the dermis. MMP-1 is an enzyme also known as interstitial collagenase and fibroblast collagenase. MMP-1 is expressed in migrating keratinocytes via ligation of the α2β1 integrin with dermal collagen and is a reliable marker of activated keratinocytes in wounded human skin. Other factors, including smoke [27] and UV exposure [28], induce MMP-1 expression, leading to premature skin aging. The Melissa officinalis phytocomplex at 0.05% w/w shows a moderate protection activity against infrared irradiations by totally preventing the IR-induced elastin alteration ( Figure 8). The higher concentration (0.1%w/w) of the phytocomplex shows a good protection activity against infrared irradiations by totally inhibiting the elastin alteration and MMP1 release induced by IR exposure (Figure 10). These results indicate that the Melissa officinalis phytocomplex at 0.1% w/w may protect the skin against the damages of oxidative stress and blue light by reduction of Nrf2 activation. In addition, the product protects the skin against the infrared irradiations damage by the inhibition of elastin alteration and MMP-1 release. | 19 |
236371514 | matrices (ECM), which greatly contribute to biomaterials design to stimulate tissue regeneration. Herein, the recent advances in electrospinning technology for 3D production of ECM-mimicking biomaterial scaffolds are systematically summarized and the applications in neural, cardiac, bone, skin, and vascularized tissue regeneration are thoroughly discussed. Challenges and future scopes related to each fi eld of tissue regeneration are discussed after each subsection. A few examples of liver, kidney, esophageal tissue engineering are also discussed. Finally, the key challenge in the cost-effective upscale of the electrospinning technique to mature and prevalent industrial applications is outlined. Herein, a systematic, thorough summary of the recent evolutions in electrospinning and its emerging applications for a broad range of tissue regenerations is provided. | 1 |
236371514 | Introduction Tissue regeneration is a rapidly evolving and interdisciplinary field at the intersection of life science, biology, material science, and engineering. Centrally, it involves functional cell-free or cell-laden constructs or biomaterial scaffolds that are fabricated utilizing various strategies. [1] Cell-free biomaterial scaffolds implanted directly at the sites of injury may mechanically support local cells to promote local tissue repair. [2] Furthermore, they can be functionalized both on the surface or in the interior with bioactive materials to stimulate regeneration of functional tissues. [3] In cell therapy applications, cell-laden constructs may enhance both survival and differentiation of the therapeutic cells compared with cell transplantation alone. The grafted cells may then ideally replace lost tissue and/or exert beneficial effects on the host tissue. [4] Among different biomaterial constructs, 3D fibrous scaffolds recreate a 3D microenvironment, which closely resembles the native extracellular matrix (ECM), including both structural and biochemical properties that guide cell survival and differentiation. [5] Scaffolds with fibrous networks possess unique characteristics, including sufficiently high interconnected porosity, high specific surface area, tunable mechanical properties, as well as optimal morphological features. The high porosity of the fibrous scaffolds facilitates mass transfer for effective nutrient supply, oxygen diffusion, metabolic waste removal, and enhancement of intercellular communications, consequently allowing high cell viability and function throughout the entire scaffold. [6] In addition, compared with 2D culture, the 3D cell culture provides a more realistic biochemical and biomechanical microenvironment, [7] creating an optimal environment for cell migration, proliferation, and differentiation. Hence, nanofibrous scaffolds with appropriate biomechanical properties are highly suitable for tissue engineering. [8] Electrospinning, as a relatively simple and versatile fiber preparation technique, has been developed to create fiber-based constructs in combination with cells, bioactive molecules, proteins, and biocompatible nanomaterials. [9] Many studies have demonstrated that the electrospinning technology has the potential for significant progress within the field of tissue regeneration. Chen et al. [10] summarized the methods for producing electrospun 1D nanofiber bundles, 2D DOI: 10.1002/smsc.202100003 Electrospinning is considered the most versatile micro-/nanofiber fabrication technology. The electrospun fibers hold high surface area, desired mechanical properties, controlled topography, as well as the ease of biochemical functionalization. The 3D electrospun fibrous structures closely mimic the hierarchical architecture and fibrous features of the extracellular matrices (ECM), which greatly contribute to biomaterials design to stimulate tissue regeneration. Herein, the recent advances in electrospinning technology for 3D production of ECMmimicking biomaterial scaffolds are systematically summarized and the applications in neural, cardiac, bone, skin, and vascularized tissue regeneration are thoroughly discussed. Challenges and future scopes related to each field of tissue regeneration are discussed after each subsection. A few examples of liver, kidney, esophageal tissue engineering are also discussed. Finally, the key challenge in the cost-effective upscale of the electrospinning technique to mature and prevalent industrial applications is outlined. Herein, a systematic, thorough summary of the recent evolutions in electrospinning and its emerging applications for a broad range of tissue regenerations is provided. nanofiber membranes, and 3D nanofiber scaffolds and indicate the possible combinations of electrospinning with 3D printing, flexible electrodes, and microfluidics for biomedical applications. Ogueri et al. [11] reviewed electrospinning in matrix-based regenerative engineering, focusing mainly on musculoskeletal tissues. Sun et al. [12] discussed electrospinning techniques for fabricating 3D nanostructures, and He et al. [13] summarized electrohydrodynamic-based bioprinting techniques, including near-field solution electrospinning, melt electrowriting, and electrospray cell printing. There are recent reports of advances in tissue regeneration of bone, [14] skin, [15] vascular, [16] and cardiac tissue. [17] However, comparatively few reviews extensively discuss in-depth fabrication processes together with bioengineering of diverse tissues. This review aims to update and summarize the most recent advancements in electrospinning technique toward fabricating 3D scaffolds, while also thoroughly reviewing emerging applications in neural, cardiac, bone, skin, vascular, liver, kidney, and esophageal tissue regeneration (Figure 1). After discussing the breadth and depth of electrospun fiber biomaterials, we outline the key challenges and future perspectives of electrospinning for tissue regeneration. | 2 |
236371514 | Advancement of Electrospinning in 3D Production Electrospinning is a highly versatile scaffold fabrication technique that combines an electric field with spinning to draw polymer solutions into micro-or nanofibers. The typical electrospinning setup is composed of four essential elements: 1) a syringe pump with a syringe that supports a stable flow of polymeric fluid through a flat-tipped stainless-steel needle to the initial jet point; 2) a high-voltage power supply that provides a robust electrostatic force drawing the polymeric solutions into polymer jets; 3) a fume hood that can remove solvent evaporation from polymer jets and accelerate the solidification process during spinning; and 4) a metal collector plate for collecting the fibers. In the most commonly used electrospinning configurations, the stainless-steel needle is connected with high voltage, and the collector is grounded. Some modified electrospinning devices use an opposite connection or a dual electrode with both positive and negative voltage. To further improve the electrospinning process, modifications of the spinneret/collector and addition of an assisted magnetic/electric field have been proposed in the literature. A graphical illustration of a simple electrospinning device and different modified electrospinning configurations are shown in Figure 2. Conventional electrospinning is known for fabricating densely packed submicrometer fibers. Simply increasing the electrospinning time is the easiest way to obtain scaffolds with a certain thickness. However several hours of electrospinning only increases the scaffold thickness by %0.14 mm, [18] due to the loss of electrostatic force after insulating the collector with the collected fibers. Template-assisted electrospinning is one of the derived electrospinning techniques, which is done by modifying the shape of the collector. Using an insulated poly(methyl methacrylate) (PMMA) mask on the collecting copper plate to focus the collection of fibers, it is possible to produce scaffolds with 3 mm thickness in a relatively short time. [19] The architecture of the fiber collector plates may be modified as well, to yield a template, which makes it possible to create customized 3D structures. Template-assisted collectors are usually designed using either a computer-aided design (CAD) program [20] or conventional textiles. [21] Many shapes such as honeycomb-like, [22] helical spring, [23] metal pin, [24] and micropatterned structures [25] have been designed for various purposes. Furthermore, some biomimetic collectors, including auricle-shaped [26] and vascular-like [27] collectors, have been designed to be used for unique biomimetic tissue applications. The template itself may also be added to or produced in the process of electrospinning. For instance, microice crystals formed during low-temperature electrospinning under high humidity were found to act as removable pore templates between the fibers. This resulted in enlarged distance between fibers, producing a 3D loosely packed architecture. [28] Similarly, Park et al. proposed a method based on NaCl templates. [29] Here they found that NaCl crystals increased the pore size of the electrospun fibers, improving cell proliferation within the scaffold. Template-assisted electrospinning has furthermore been used in combination with microfluidic devices to improve the cell culture conditions under continuous flow. [30] Alternatively, self-assembly electrospinning can be used to increase the scaffold thickness and obtain 3D structures. Due to fast solidification from the polymer jets and the electrostatic attraction between the fibers on the grounded collector and the charged jets, the scaffold structure may grow toward the charged jets, thereby forming 3D structures with a thickness reaching more than 10 cm. [31] Honeycomb-patterned structures fall into the self-assembly electrospinning category due to the electrostatic repulsion between adjacent fibers. [32] This type of structural network has been intensively investigated due to the similarity to the osteon structure. [33] The choice of polymer solution (polymer solutes and solvents) is the dominant effective factor when modifying the scaffold thickness in self-assembly electrospinning. Other parameters, such as applied voltage, polymer concentration, and flow rate, etc., have less effect. So far, polystyrene (PS), [31] polyacrylonitrile (PAN), poly(vinyl alcohol) (PVA), polyethylene oxide (PEO), [32] and their hybrids [34] reportedly exhibit self-assembly properties during electrospinning. It is worth mentioning that surfactant coating (Beycostat A B09) [35] and emulsion [36] likewise promote the self-assembly electrospinning process. As the electrostatic interactions and solidification rate are factors difficult to quantify, the optimization of selfassembly electrospinning is still under investigation. Generally, the collector type is a significant element in electrospinning and makes a great impact on the surface topography and the 3D geometry of the scaffolds. One type of collector is a coagulation bath in a metal container, which leads to liquidassisted collection, also called wet electrospinning. [37] Ethanol, [38] mixed ethanol/water solution, [39] hexane, [40] or subcritical CO 2 fluid [41] have been used as coagulating agents. In addition, some of the chemicals in the solutions may induce crosslinking [42] or functional surface coating on the fibers. [38a,43] An important aspect to consider for the collector bath is the surface tension of the collector solution. Solutions with low surface tension for target fibers create loosely packed 3D fibrous scaffolds. Conversely, solutions with high surface tension resemble a traditional collector plate, where the fibers are collected on top of the solution, resulting in densely packed fibers. It is noteworthy that electrolyte solutions (e.g., KCl solutions) can act as a ground collector that combines the functions of the metal container and the coagulation bath into one. This yields a more effective way to fabricate free-standing, complex nanofiber architectures according to the designed patterns. [44] High humidity [45] and immersions [46] are variations of the wet electrospinning technique. Wet electrospinning has further been combined with a rotating collector, [39a,42b] layer-by-layer [47] electrospinning, and template electrospinning [44] for various 3D scaffolds. In addition, post-treatment with immersion and freeze drying may be helpful in transforming dense electrospinning membranes into loosely packed 3D structures. [48] Further improvements have been made to the traditional electrospinning technique, such as applying an x-y translational motion collector, similar to the one used in standard 3D printing. [49] Utilizing the jetting initiated prior to the onset of bending stability, high-precision and direct-write deposition of microfibers have been achieved by decreasing the electrospinning distance, a technique called near-field electrospinning (NFE). As an extension to NFE, the atomic force microscope (AFM) system (AFM-based voltage-assisted electrospinning) allows fabrication of nanofibers in a controllable fashion via polymer deposition from an AFM probe. [50] Initially, NFE was mainly applied for polymers dissolved in solvents. [51] As evaporation of solvents may affect the precision of the fiber deposition, [52] solvent-free electrospinning was introduced to the field of NFE in 2008, creating the emerging melt electrospinning writing (MEW) technology. [53] Although MEW makes it possible to achieve high-resolution nanostructures with tunable coil densities [54] and precise deposition of single fibers, [49] it cannot achieve wide-range regulation in height. This challenge must be overcome before MEW is fully applicable in the construction of artificial organs. Combining MEW with template-assisted collectors could be one way of addressing this limitation. [55] Besides using NFE and MEW, controlled deposition of fibers has been achieved using an additional magnetic/electric field to standard electrospinning. Using a cylindrical side-wall electrode and a sharp-pin ground electrode, the electrospinning jet was focused and a patterned nanofibrous mat was fabricated. [56] However, until now, aligned architecture and tunable deposition area have only been achieved for bundles of fibers. [57] Inspired by MEW, polymer melts may possibly be utilized in future fieldassisted electrospinning techniques to potentially yield precise control of single-fiber deposition. [49,58] Field-assisted electrospinning could become the next-generation leading electrospinning technique for single-fiber deposition. Last but not the least, layer-by-layer electrospinning may be the most flexible strategy. It combines not only different electrospinning methods, [59] but also other technologies, such as cell layer and electrospinning layer, [60] 3D printing layer and electrospinning layer, [61] and electrospraying layer and electrospinning layer. [62] Table 1 shows the six electrospinning techniques covered in this Review with their pertinent features and limitations. It is foreseen in the future that even more techniques could be incorporated into the versatile electrospinning platform. | 3 |
236371514 | Tissue Regeneration Based on 3D Electrospun Scaffolds 3D electrospun scaffolds can help fabricate highly porous structures with biomaterials mimicking the natural 3D extracellular microenvironment for improved cell adhesion, proliferation, and differentiation. [54,63] 3D electrospun scaffolds display strong potential in tissue regeneration through their biochemical cues from natural, synthetic, or hybrid biomaterial selections and physical cues from the mechanical, topographical, and geometrical features of the fiber constructs. [38b,64] Most recent studies have focused on producing 3D bioactive and biocompatible scaffolds with potential applications in fields such as neural, cardiac tissue, and bone tissue regeneration. [63c,65] The following sections seek to give an in-depth description of the role of electrospinning as a tool in tissue regeneration applications. | 4 |
236371514 | Cardiac Tissue Regeneration Cardiovascular diseases are the leading course of death compared with any other disease, affecting millions of people globally and significantly decreasing their quality of life. [99] The human heart has low regenerative properties, making this tissue very vulnerable to injuries such as myocardial infarction (MI). After MI, the injured tissue is replaced by scar tissue, leading to great loss of the contractile ability, which consequently may lead to heart failure. For these reasons, cardiac tissue regeneration may be the key to restoring the contractile ability of the heart after an injury caused by cardiovascular disease. [100] 3D electrospun structures can mimic the ECM of the myocardium, providing a nanofibrous microenvironment for cardiac cell adhesion, maturation, and function. Loosely packed 3D PPy scaffolds can enable stable electroactive cellÀfiber construct formation and promote cell proliferation compared with a traditional 2D electrospun PPy fiber mesh. [65a] Wet-electrospun 3D alginate/ gelatin hydrogel scaffolds were found to support the maturation of human iPS cell-derived ventricular cardiomyocytes. [42c] Likewise, 3D PCL nanofibrous scaffolds have been reported to directly promote cardiomyocyte differentiation through Wnt/ β-catenin signaling. [101] 3D electrospun fibers have been manufactured from different ECM proteins, to provide suitable substrates for cardiac tissue regeneration. A scaffold containing the abundant ECM protein collagen maintained cardiomyocyte contractile function for a period of 17 days with high levels of desmin expression. [102] ECM decellularized from the porcine ventricular tissue has been reported to provide natural cardiac ECM compositionally. [9d,103] Besides ECM proteins, the use of other naturally derived proteins, such as keratin [104] and SF [105] that are easy to obtain, have likewise been investigated. Fibrous scaffolds manufactured from SF have been reported to enhance cell commitment of adult rat cardiac progenitor cells. [105] Collectively, 3D electrospun scaffolds have been shown to exhibit improved performance for cardiomyocyte culturing compared with regular flat culture systems. A 3D cardiac patch-based system has emerged as a potential regenerative strategy, as shown in Figure 7A. In this study, SF-modified CA 3D nanofibrous patches were used to restrain pathologic ventricular remodeling post-MI by attenuating myocardial fibrosis. [106] The patch/adipose tissue-derived(AD)-MSC group showed increased viability of engrafted AD-MSCs ( Figure 7B,C), expression of cardiac paracrine factors ( Figure 7D), reduced fibrotic area ( Figure 7E), and improved density of neovascularization ( Figure 7F) compared with the intramyocardially injected AD-MSC group and untreated groups. These results indicated that the 3D electrospun patch could be a good carrier, which allows high retention and survival of the engrafted AD-MSCs. As the human heart is a pulsating tissue, the mechanical properties are very important to consider when developing a cardiac patch. For this reason, cell-laden polycarbonateÀurethane (PCU) scaffolds have received much attention, due to their optimal Young's moduli (0.75 MPa, PCU electrospun on polyester fabric template), comparable with that of a human heart. The scaffold allowed prolonged spontaneous synchronous contractility of rat cardiac myoblasts on the entire engineered construct for 10 days in vitro at a near-physiological frequency of %120 bpm. [21] As a cardiomyocyte is a muscle cell, ES and directional arrangement are crucial. Therefore, conductive scaffolds have gained great interest in cardiac tissue regeneration in recent years. In one study, cardiac cells were seeded on nanogold-coated PCLÀgelatin scaffolds, which lead to cellular assembling of elongated and aligned tissues. [107] In another study, conductive PLLA/PANI nanofibrous sheets were found to promote cardiac differentiation measured in terms of maturation index and fusion index. [108] Others have focused on designing electrospun scaffolds to guide cell growth in precise directions. Cardiac cells cultured on aligned electrospun nanofibers were found to exhibit elongation and orientation of the α-actin filaments, [109] while simultaneously displaying high expression of genes encoding a number of sarcomere proteins, calcium-handling proteins, and ion channels. [110] Ultimately, multifunctional cardiac patches consisting of various tissue layers conducting different functions could be a promising solution for cardiac transplantation. A bottom-up approach was proposed to assemble an impressively complex modular tissue ( Figure 8A). [1c] Through analyzing collagen fiber orientation in adult rat hearts, Fleischer et al. [1c] found that the alignment from the epicardial side to the endocardial side was a 100 shift ( Figure 8B), which they used to guide the assembling of artificial multilayers by assembling several tissue layers on top of each other. Microholes (40 AE 0.8 μm) on the ridges of each layer were developed to ensure sufficient mass transfer (exchange of nutrients and oxygen) ( Figure 8C). The grooved scaffolds were stacked with a slight angle shift to mimic the collagen fiber orientation in adult rat hearts ( Figure 8D). The cells in the grooved scaffolds were found to assemble into aligned cardiac cell bundles similar to that of the natural cardiac microenvironment with a higher expression of connexin 43 proteins (green color) due to the electrical coupling between adjacent cells ( Figure 8E). Furthermore, double-emulsion PLGA microparticles ( Figure 8F) with VEGF were deposited into the cages of "channel þ cages" layer ( Figure 8G), thus creating a controlled release system for continuous supply of vascularization signals. Microtunnels with dimensions of 450 μm were patterned between cage-like structures for endothelial cells to form large, closed lumens. In addition, Fleischer et al. designed another layer with cage-like structures, and PLGA microparticles containing dexamethasone (DEX), an anti-inflammatory agent, were scattered on top ( Figure 8H,I) to attenuate the activation of macrophages and thereby decrease the immune response after transplantation. The PLGA microparticles were found to enable the long-term release of VEGF and DEX ( Figure 8J). A macroscopic view of the patches in rats and a cross sectioning of the patches revealed that the layered structure was maintained 2 weeks posttransplantation ( Figure 8K). The layers of the developed scaffold were found to mimic both the stiffness and the mechanical anisotropy of the heart muscle, hence improving the potential for the scaffolds to be integrated properly to the heart muscle. Table 3 shows the characteristics of 3D electrospun scaffolds designed for cardiac tissue regeneration. Scaffold functionality in terms of bioactivity, aligned topography, and conductivity should still be improved to advance the potential of 3D electrospun scaffolds in the field of cardiac tissue regeneration. Based on the complexity of cardiac tissue, the ultimate goal of cardiac tissue regeneration is to achieve one scaffold with great diversity of functional elements to mimic the natural cardiac tissue. | 6 |
236371514 | Bone Tissue Regeneration As osteoporosis can increase the risk of bone fracture, it is the leading cause of broken bones among the elderly. For large bone defects beyond the ability of self-regeneration, artificial scaffolds are necessary to bridge the gap, assist cell adhesion, and accelerate repair. This method is not only applicable for the elderly but may also be helpful to younger people by greatly decreasing the healing time. Importantly, advances in 3D electrospun scaffolds as bone substitutes are enhancing our ability to create ideal ECM mimicking structures for bone regeneration. [111] The 3D electrospinning technology is a well-established nano-/microstrategy used to manufacture biomimetic fibrous constructs for bone tissue regeneration. A special 3D honeycomb-like architecture has been proposed to support osteogenic differentiation by enhancing alkaline phosphatase (ALP) production, calcium deposition, and specific gene expressions. [65b] In another study, conducted by Sankar et al., a 3D-patterned electrospun scaffold was seeded with human AD stem cell spheroids. Osteodifferentiation was reportedly enhanced without the need for an osteoinductive culture medium. [112] The scaffold shape can also be designed to match specific bones, such as the lumbar vertebra, as described by Su and coworkers. [54] In vitro, 3D electrospun scaffolds support cell development. Human osteosarcoma cells cultured on piezoelectric hydrophilic electrospun PVDF scaffolds showed well-defined actin stress fibers crossing the cell ( Figure 9A), and the scaffold was found to generate a local electric field that activated the osteoblasts ( Figure 9B). [113] The surface potential of PVDF fibers, furthermore, was found to regulate the production of mineralized collagen, a key component of the bone matrix, thus promoting the processes of bone regeneration. [114] More complex electrospun scaffolds have allowed reversible dynamic mechanical stimulation for the study of cell response to mechanical forces. A thermocontrollable and stiffness-tunable 3D electrospun microfibrous poly(N-isopropylacrylamide) scaffold was used to submit cells to alternating cycles of mechanical stimulations by switching scaffold resistance between soft and stiff. The scaffold was reported to initiate cytoskeletal organization and cell shape deformation to activate the Yes-associated protein (YAP) as well as the preosteogenic runt-related transcription factor 2 (RUNX2), which is known to mediate mechanotransduction and differentiation ( Figure 9C). [115] Besides providing mechanical stimulation, reverse thermosensitive polymer fibers have also been used to support MSCs within 3D mechanically stable PCL. [116] Incorporating bioactive inorganic materials with electrospun polymers, mimicking the native bone ECM, has gained tremendous interest for bone tissue reconstruction throughout the years. Various modified and unmodified apatite minerals have been proven to resemble the physical properties of the natural bone tissue and promote osteogenic cell function. Beta-tricalcium phosphate (β-TCP), [117] silicate-containing hydroxyapatite, [118] and boron doped hydroxyapatite (B-HAp) [119] have been proposed as bone-like biomaterials mimicking the hierarchical architecture and chemical composition of the bone ECM. In one study, hydroxyapatite was incorporated in layer-by-layer electrospun honeycomb PCL fibers using electrospraying (Figure 10Aa,b), mimicking the natural environment for maxillofacial bone reconstruction. [33] Both reverse transcription-quantitative real-time PCR (Figure 10Ac) and ALP activity (Figure 10Ad) results clearly supported the positive effect of the honeycomb scaffolds on differentiation toward the bone lineage in the absence of any small-molecule osteoinductive agents. Furthermore, the honeycomb structure resulted in significantly higher migration of cells from explanted bone tissue onto the scaffold compared with random PCL fibers. (Figure 10Ae). A natural occurring material, diatom shell, was incorporated into a 3D electrospun scaffold and was found to improve bone tissue regeneration. [120] Another material that has been studied in regard to bone tissue regeneration is ZnO nanoparticles. Due to their osteoconductive and antibacterial properties, they were electrospun into PCL and demonstrated great potential for treatment of periodontal defects ( Figure 10B). [121] Another advantage of electrospun fibers is their capability to act as a great drug carrier or release system. In several studies, 3D electrospun scaffolds have been coated with bone morphogenetic protein-2 (BMP-2) on the surface by hydrogel or polydopamine (pDA)-assisted immobilization and physical adsorption. This approach was biocompatible and osteoinductive in vitro and in vivo in a pilot study in rabbits. [122] A low dose of recombinant human BMP-2 has likewise been incorporated into 3D PCL/PLA scaffolds and promoted osteogenic differentiation and facilitated new bone formation after 6 weeks of implantation in vivo. [123] In another study, rifampicin was incorporated in 3D electrospun scaffolds to successfully prevent bone infection, resulting from implant or orthopedic surgery. [124] Alendronate, a nitrogenous bisphosphonate widely used in the therapy of metabolic bone diseases, was incorporated into electrospun scaffolds and promoted osteogenesis-related gene expression in human fetal osteoblasts. [125] Finally, Xu et al. produced electrospun SF/poly(L-lactide-co-ε-caprolactone) (PLCL) coreÀshell fibers that c) Percentage of activated cells grown on different PVDF scaffolds. d) Schematic representation of a cell cultured on hydrophilic electrospun PVDF scaffold; ES, coming from the 3D fibrous scaffold bending due to the cell forces applied upon attachment, causes the opening of plasma membrane channels (VGCC, SACC), which lead to an increase in calcium ions in the cytoplasm. A,B) Reproduced with permission. [113] Copyright 2019, Royal Society of Chemistry. C) Temperature-dependent changes a) in swelling ratio of crosslinked microfibrous hydrogels in response to temperature alternations. b,c) Ability of RD-MS to alter hMSCs underlying YAP and RUNX2 signaling activation after 7 days. Reproduced with permission. [115] were used to dual-deliver the osteoinductive peptide H1 from the core and HAp from the shell for collectively enhancing osteogenesis both in vitro and in vivo. This was proven by increased expression of osteopontin ( Figure 10C) and induced bone mineralization ( Figure 10D) compared with control scaffolds. [126] Table 4 shows different 3D electrospun scaffolds used for bone tissue regeneration. In the field, the cues of bioinorganic, electromechanical, and mechanical stimulation have been the main research direction in the recent years. Scaffolds with drug-carrying or releasing properties have also gained tremendous attention with a large number of published reports. All the electrospun scaffolds implanted in animal models mentioned in this Review were uncellularized, designed to stimulate the animal's own cells to produce new bone. However, it would be ideal to stimulate cells in vitro to form artificial bone with the same properties as native bone. The shape of artificial bone can be controlled by the shape of electrospun scaffolds by combining it with either 3D printing, MEW, NFE, or field-assist electrospinning. | 7 |
236371514 | Vascular Tissue Regeneration If tissue regeneration of tissues larger than 200 μm ever is to succeed, the field needs to overcome the challenge of creating fully functional blood vessels. Vascularization of tissues is essential for supplying the cells with nutrients and oxygen and to help remove waste products. [127] Su and coworkers developed an artificial multihelix electrospun PCL/PCL þ PEO scaffold. [128] Here, the seeded human umbilical vein endothelial cells (HUVECs) were reported to exhibit a preferential cell distribution of around 86% on the PCL side rather than the PCL þ PEO side, resulting in a distinctive 3D Janus cellular pattern with increased vinculin and phosphorylated-focal adhesion kinase (pFAK) expression. Kim et al. developed a vascularized 3D tissue by stacking HUVEC cell sheets with skeletal myoblasts and fibroblast cell sheets in a layer-by-layer construction. [59c] In another work, the thickness of a vascularized tissue construct was controlled by the thickness of the electrospun scaffold through the increasing layer number. [129] Besides solution electrospinning, MEW [33] Copyright 2018, American Chemical Society. B) Rat periodontal defect model. Reproduced with permission. [121] Copyright 2017, Wiley-VCH. C) Immunofluorescence images of osteogenic differentiation for hiPS-MSCs on different coreÀshell scaffolds in osteogenic medium at week 3 (blue: 4 0 ,6-diamidino-2-phenylindole, DAPI; red: osteopontin, OPN; green: F-actin). D) X-ray micro-computed tomography (μCT) analysis of the calvarial bone retrieved 8 weeks after implantation using various coreÀshell scaffolds in critical-sized bone defects. C,D) Reproduced with permission. [126] Copyright 2019, Elsevier. has been used for coculture of HUVECs and normal human dermal fibroblasts (NHDF) through cell accumulation technique, which allowed the formation of capillary-like network structures. [130] Regarding artificial blood vessel architecture, 3D electrospinning is a simple and ideal method to fabricate tubular-shaped biodegradable scaffolds. Such scaffolds have been fabricated based on either rotating mandrel collectors or post-treatments. In one study, engineered vascular grafts with diameters matching vascular vessels were prepared for vascular reconstruction by simply adjusting the diameter of the mandrel ( Figure 11A). [131] Another strategy applied for obtaining tubular constructs was an automated fabrication strategy, which rolled 2D matrices into 3D tubular constructs by continuously bonding different functional layers (cells, hydrogels, and scaffold biomaterials) with varying diameters. [132] In addition to scaffold shape, mechanical properties are key factors to consider when developing material for vascularized tissue regeneration. In one study, PU was electrospun onto an airbrushed PCL tube to mechanically reinforce the scaffold. The tensile strength and Young's modulus of the reinforced scaffolds were reported to be 67.5 AE 2.4 and 1039 AE 81.8 MPa, respectively, allowing a 2 kg dumbbell to hang from the scaffold without breaking it ( Figure 11B). [64b] Materials like polyamide-6 and GO have likewise been proven to reinforce the mechanical and physical properties of electrospun scaffolds. [131,133] By combining electrospun PCL with 3D-printed PCL, both surface morphology and mechanical properties were found to be suitable for vascular reconstruction ( Figure 11C). [134] Another approach to obtain mechanically reinforced scaffolds is using multiple electrospun layers with different architectures. Such a scaffold was designed using longitudinally aligned nanofibers (inner and outer layer) and radially aligned nanofibers (middle layer) and successfully mimicked native artery structure ( Figure 11D). [135] Similarly, the NFE technique combined with electrospraying and electrospinning produced a mechanically reinforced threelayered scaffold with highly aligned strong fibers, which provided appropriate mechanical support for HUVECs in vitro and allowed infiltration of host cells after implantation into the abdominal aorta in vivo. [136] Ju and coworkers [137] manufactured a bilayered electrospun and cellularized vascular scaffold and assessed its preclinical feasibility in sheep. The electrospun scaffold was composed of randomly orientated fibers in the inner layer and aligned fibers in the outer layer ( Figure 12A). The scaffold was seeded with smooth muscle cells (SMCs) and endothelial cells and preconditioned using a pulsatile bioreactor system ( Figure 12B) prior to transplantation. The cellularized vascular constructs were found to maintain a high degree of graft patency with a constant luminal diameter ( Figure 12C), structural integrity with compliance ( Figure 12D), and contractile properties without eliciting an inflammatory response after a 6-month implantation period. Consequently, this scaffold was reported as a clinically applicable alternative to traditional prosthetic vascular graft substitutes. Ahn et al. improved the cell seeding efficiency on vascular-like electrospun PCL and collagen type I fibers, by prefabricating an SMC sheet. The cell sheet was wrapped around the electrospun vascular scaffolds and found to significantly enhance not only the Human-induced pluripotent stem cellderived MSCs (hiPS-MSCs) [126] www.advancedsciencenews.com www.small-science-journal.com Small Sci. 2021, 2100003 Figure 12. A) SEM images of entire layer, outer layer, cross-sectional interface and inner layer of the bilayered vascular scaffold. B) Bioreactor setup consisting of a computer-programmed gear pump, flow reservoir, and the bioreactor housing unit. C) Inner diameter measurement of the transplanted engineered blood vessels revealed a stable lumen caliber for the duration of the 6-month follow-up. D) A representative CT scan shows the absence of an aneurysm along the entire length of the transplanted engineered blood vessel (arrows). A-D) Reproduced with permission. [137] Copyright 2017, Elsevier. Copyright 2018, Elsevier. C) Schematic illustration of the process used to fabricate 3D tubular artificial vascular scaffolds combining electrospinning with 3D-printed coating. Reproduced with permission. [134] Copyright 2015, Royal Society of Chemistry. D) Longitudinal view of photographic and scanning electron microscopic images of electrospun trilayered tubular scaffolds as well as the fast FFT analysis. Reproduced with permission. [135] Copyright 2018, Elsevier. E) Prefabricated cell sheets wrapped around an electrospun scaffold. Reproduced with permission. [138] Copyright 2015, Elsevier. F) Schematic of multilayer graft fabricated by electrospun tubular scaffold and hydrogel. Reproduced with permission. [140] Copyright 2018, Elsevier. G) The photo of an electrospinning collector with copper wire wound around it and the interior copper wire being easily pulled out. Grooves and cross-sectional morphology of the scaffold. Reproduced with permission. www.advancedsciencenews.com www.small-science-journal.com Small Sci. 2021, 2100003 cell seeding efficiency, but also the maturation process and the cell-to-cell junctions compared with cells seeded directly on the electrospun fibers, yielding an implantable vascular graft ( Figure 11E). [138] Wang et al. [139] used the molecule-releasing properties of electrospun fibers. Here, resveratrol, a natural polyphenol, was incorporated into electrospun PCL fibers, allowing sustained and controlled release that was found to enhance the vascular regeneration process by promoting migration of endothelial cells and tube formation. Another study conducted by Post et al. [140] showed that designing a layered cell-free hydrogel system likewise led to rapid endothelialization ( Figure 11F). Hydrogels have also been used to coat electrospun scaffolds with copper wire-induced grooves ( Figure 11G) using a so-called dip-coating method. This technique promoted the attachment of HUVECs. [63b] The hydrogels can increase hydrophilicity, biocompatibility, and mechanical strength and therefore improve affinity between cells and the electrospun nanofibers. To overcome the challenge of anatomic differences between individual patients, Fukunishi et al. developed a patient-specific vascular graft. A 3D-printed patient-specific stainless steel graft was used as an electrospinning collector, allowing both SMC engraftment and endothelialization; hence, this method was found to be a promising technology for future vascular tissue regeneration. (Figure 11H). [20] Table 5 shows the 3D electrospun scaffolds for vascularized tissue regeneration highlighted in this Review. There are relatively few studies published on biological activity, cellular interaction, and drug release compared with other fields of tissue regeneration. This might, however, be explained by the intense focus on optimizing scaffold shape and mechanical properties for vascularized tissue regeneration. For this field to reach its full potential, future studies should closely examine both vascular cell response and scaffold architecture. | 8 |
105853494 | A tactically new approach to the asymmetric synthesis of the piperidine alkaloids (+)-coniine, (−)-coniceine, (+)-β-conhydrine, (+)-sedamine and (+)-allosedamine has been developed. The key step is the elaboration of the piperidine template equipped with suitably functionalized appendages at the stereodefined C-2 position. Subsequent manipulation of the appropriate functionalities gave rise to the targeted compounds in high yields and high level of enantioselectivity. Introduction The piperidine ring is a ubiquitous structural feature of numerous naturally occurring alkaloids and can be frequently recognized in the structure of drug candidates [1]. The interest in piperidine alkaloids is well displayed by the wealth of published material detailing their sources and biological activities and their structural diversity makes them interesting proving grounds for organic chemists. As a consequence numerous methods have been developed for the synthesis of substituted piperidines in a stereoand enantioselective manner [2] and interest in their chemistry continues unabated. Piperidine alkaloids incorporating a stereogenic center at C-2, as exemplified by (+)coniine (1), (−)-coniceine (2), (+)-β-conhydrine (3), (+)-sedamine (4) and (+)-allosedamine (5) (Figure 1), fall into this category and consequently have attracted considerable attention from the synthetic community. Objectives and Synthetic Strategy We were then interested in developing a feasible and highly stereoselective route giving rise to the specific embodiment of these piperidine alkaloids presented in Figure 1. The salient features of the synthetic strategy are (i) the early creation of the C-2 stereogenic center of the piperidine unit on reliance with the highly diastereoselective 1,2-addition on chiral SAMP-hydrazones [3] and (ii) the creation of the piperidine template by ring closing metathesis which ranks highly in the hierarchy of synthetic tactics for the elaboration of nitrogen containing ring systems [4]. N Pr H (+)-Coniine (1) N (-)-Coniceine (2) N H OH H (+)-β-Conhydrine (3) N Ph H Me OH N Ph H Me OH (+)-Sedamine (4) (+)-Allosedamine (5) Figure 1. Enantioselective Synthesis of (S)-(+)-Coniine (1). Extension to the Synthesis of (−)-Coniceine (2). To test the viability of our conceptually new synthetic approach the synthesis of the structurally simple piperidine alkaloid (+)-coniine (1) was envisaged since it was anticipated that its elaboration could serve as a testing ground and provide foundation for extension to more complex and functionalized systems. 1. (S)-(+)-Coniine (1) The first facet of the synthesis was the assembling of the requisite dienehydrazide 8a, which was readily obtained by the three-step sequence depicted in Scheme 1. This olefinic precursor was obtained essentially as single diastereoisomer detectable by NMR making evident the high selectivity of the initial diastereofacial 1,2-addition process allowing introduction of the absolute stereochemistry early in the sequence. RCM reaction with Grubb's second generation ruthenium catalyst proceeded uneventfully to afford diastereopure enehydrazide (S,S)-9a. Catalytic hydrogenation afforded hydrazide (S,S)-10a and subsequent treatment of (S,S)-4a with BH3 . THF triggered off the formation of the NH free model with the concomitant release of the chiral appendage, thereby providing high yield of the targeted alkaloid 1 with excellent enantioselectivity. | 1 |
105853494 | Introduction The piperidine ring is a ubiquitous structural feature of numerous naturally occurring alkaloids and can be frequently recognized in the structure of drug candidates [1].The interest in piperidine alkaloids is well displayed by the wealth of published material detailing their sources and biological activities and their structural diversity makes them interesting proving grounds for organic chemists.As a consequence numerous methods have been developed for the synthesis of substituted piperidines in a stereo-and enantioselective manner [2] and interest in their chemistry continues unabated. | 2 |
105853494 | Objectives and Synthetic Strategy We were then interested in developing a feasible and highly stereoselective route giving rise to the specific embodiment of these piperidine alkaloids presented in Figure 1.The salient features of the synthetic strategy are (i) the early creation of the C-2 stereogenic center of the piperidine unit on reliance with the highly diastereoselective 1,2-addition on chiral SAMP-hydrazones [3] and (ii) the creation of the piperidine template by ring closing metathesis which ranks highly in the hierarchy of synthetic tactics for the elaboration of nitrogen containing ring systems [4]. | 3 |
105853494 | Enantioselective Synthesis of (S)-(+)-Coniine (1). Extension to the Synthesis of (− − − −)-Coniceine (2). To test the viability of our conceptually new synthetic approach the synthesis of the structurally simple piperidine alkaloid (+)-coniine (1) was envisaged since it was anticipated that its elaboration could serve as a testing ground and provide foundation for extension to more complex and functionalized systems. | 4 |
105853494 | (S)-(+)-Coniine (1) The first facet of the synthesis was the assembling of the requisite dienehydrazide 8a, which was readily obtained by the three-step sequence depicted in Scheme 1.This olefinic precursor was obtained essentially as single diastereoisomer detectable by NMR making evident the high selectivity of the initial diastereofacial 1,2-addition process allowing introduction of the absolute stereochemistry early in the sequence.RCM reaction with Grubb's second generation ruthenium catalyst proceeded uneventfully to afford diastereopure enehydrazide (S,S)-9a.Catalytic hydrogenation afforded hydrazide (S,S)-10a and subsequent treatment of (S,S)-4a with BH 3 .THF triggered off the formation of the NH free model with the concomitant release of the chiral appendage, thereby providing high yield of the targeted alkaloid 1 with excellent enantioselectivity. | 5 |
105853494 | (−)-Coniceine (2) This bicyclic alkaloid is a representative member of the biologically active indolizidine alkaloids that have been isolated from the skin secretions of neotropical amphibians [5].Its elaboration was readily achieved as depicted in Scheme 2 starting from the diastereopure (S,S)-9b.This diastereochemically enriched enehydrazide equipped with a protected hydroxypropyl appendage was accessed via the synthetic route depicted in Scheme 1 starting from the appropriate aliphatic aldehyde 6b. | 6 |
105853494 | Enantioselective Synthesis of (+)-β β β β-Conhydrine (3). This piperidine alkaloid is representative of the hemlock alkaloids isolated from the seeds and leaves of the poisonous plant Conium maculatum L. whose extracts were used in the ancient Greece to get rid of criminals and undesirable intellectuals, for example Socrates [6]. Initially we planned to synthesize the carboxaldehyde derivative 13 and we surmised that treatment of diastereopure 13 with EtMgBr would provide the potential for a direct access to the piperidine template tailed with the required hydroxypropyl appendage.The highly functionalized compound (R,S)-13 was obtained in high yield and high enantioselectivity as outlined in Scheme 3. Disappointingly, when diastereopure (R,S)-13 was allowed to react with EtMgBr a 2:3 mixture of (R,R,S)-14 and (R,S,S)-14 diastereoisomers was obtained.We then set out to achieve the alternative strategy depicted in Scheme 4 which secured the stereochemistry of the hydroxyalkyl appendage on the piperidine template at an early stage of the synthesis.Interestingly, when bis-olefin 15, readily assembled as portrayed in Scheme 4, was subjected to RCM a 55:45 mixture of diastereomerically pure 16 along with the NH free piperidine 17 was obtained.This unprecedented phenomenon had no impact on the outcome of the process since the targeted (+)-β-conhydrine (3) could be readily accessed from 16 and 17 as well.Enantioselective Synthesis of (+)-Sedamine (4) and (+)-Allosedamine (5). The 1,3-aminoalcohol moiety is found in many synthetic and natural products possessing physiological activities and is the integral part of a variety of potent drugs [7].It is also the most distinguishing structural feature of 2-(2-hydroxyalkylsubstituted)piperidine based alkaloids such as sedamine and allosedamine.This type of alkaloid has been shown to display memory enhancing properties and may be effective for the treatment of cognitive disorders [8]. A new synthetic approach to these compounds has been developed and is outlined in Scheme 5. Noteworthy, for the reduction of the carbonyl functionality of diastereopure 18 a variety of reducing agents were screened.By making use of K-selectride a 1:3 mixture of the diastereoisomeric forms 19 and 20 was obtained. | 7 |
225723454 | Fullerene nanotube was synthesized in this research by pyrolysis of plastic waste Polypropylene (PP) at 1000 ° C for two hours in a closed reactor made from stainless steel using molybdenum oxide (MoO3) as a catalyst and nitrogen gas. The resultant carbon was purified and characterized by energy dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD). The surface characteristics of C60 nanotubes were observed with the Field emission scanning electron microscopy (FESEM). The carbon is evenly spread and has the highest concentration from SEM-EDX characterization. The result of XRD and FESEM shows that C60 nanotubes are present in Nano figures, synthesized at 1000 ° C and with pyrolysis temperature 400° C. The synthesis operation doing in one reactor and limited time. | 1 |
225723454 | Introduction: Plastic materials are characterized by many properties that make them desirable in practical applications such as low cost, lightness and durability and as a result are necessary for our daily lives (1). Municipal solid waste is non-degradable and is not implemented in nature. It is disposed of by the way known as landfill, which accumulates multiple types of plastic waste. In these tombs there are many microorganisms that accelerate the degradation of organic matter associated with plastic waste (2). In many developing countries, the amount of plastic consumption is much higher than the average global consumption. The large production of plastic poses a major challenge to deal with these huge quantities of plastic waste after use. Plastic materials in solid waste release harmful chemicals in the soil that can then flow into the groundwater or other surrounding rivers and lakes so it can pose a significant risk to the organisms that drink contaminated water (3). Polypropylene is an attractive candidate for packaging applications and has a wide popularity in automobile and electronics field due to its excellent advantages of good thermal stability, chemical resistance, easy handling, good mechanical characteristics and inexpensiveness ) 4). Department of Chemistry, College of science, University of Anbar, AL-Anbar, Iraq. * Corresponding author: [email protected] 8102 -8244 -0002 -https://orcid.org/0000 ID: ORCID * Waste materials from domestic wastes to industrial remains, rise harmful effects on environmental and human health regarded as a source of air, soil, water and marine pollution. However, wastes can be used as tools to produce useful goods. A significant technique to obtain this goal is pyrolysis. Pyrolysis relates to thermal decomposition that is operated in an air-free condition (5). Pyrolysis is a probable alternative to landfill for processing plastic waste, resulting decomposition products which can be used as" fuels instead of gas, diesel or fuel oils" (6). Additionally, pyrolysis of plastics has also been utilized to manufacture various types of Nano Carbon such as nanotubes, nanofiber, Nano rods, nanowires, etc., C 60 nanotube which have high value and exceptional physical and chemical properties because of their impressive characteristic like high surface area, porous-rich structure, high conductivity and excellent chemical stability, by blending plastics and catalyst in one reactor (7). The properties of carbon nanotubes and the percentage of the product depend mainly on raw materials. For instance, various methods have been developed to produce CNTs such as arc discharge, pyrolysis, laser ablation of carbon, plasma assisted deposition and chemical vapor deposition (CVD) (8)(9)(10). Fullerene is any molecule in the form of an ellipsoid, tubular or a hollow sphere structure composed entirely of carbon. They are generally referred to as "Buckyballs" (11). There are many types of fullerene such as C 60 rods and C 60 tubes (12). The research objectives are to increase the economic value to benefit from plastics waste and assist in addressing environmental problems associated with this waste and produce new nanomaterials that inter into the technological industry. | 2 |
225723454 | Preparation of system gas The nitrogen gas bottle was connected to three traps, the first trap contained concentrated sulfuric acid (H 2 SO 4 ), which absorbed water from the gas, then the gas was passed to the second trap which contained a saturated solution of pyrogallol to absorb oxygen from the gas, finally the gas was passed to the magnesium sulphate (MgSO 4 ) to absorb the rest of the acid. Then the gas was passed to the reactor system through a trap. | 3 |
225723454 | Methods The samples were washed, air-dried and shredded into small pieces of an area that's around 1mm². 25 g of shredded PP was placed inside a stainless-steel reactor that is filled with some inert gas (nitrogen) at low pressure (between 50 and 70 mbar). 0.5 g of (MoO 3 ) catalyst was placed in tube nozzle connected with reactor. The reactor was tightly closed and put in an electric furnace to be heated as shown in Fig.1. This reactor is connected to condenser and then to three neck round-bottom flask for products collection. Nitrogen gas was pumped at 25 ° C until the temperature reached 500 ° C. The temperature of the furnace was gradually raised. When the temperature of 400 ° C was reached and the wastes began to decompose, the catalyst was added from the tube nozzle. At this level the distillation process began and at the end of distillation the temperature was raised to required temperature. We used 1000 ° C for two hours, at a heating ramp rate of 13 °C/min, then allowed to cool to room temperature naturally. It was found that the final product in the reactor included carbon powder. | 4 |
225723454 | X-Ray Diffraction (XRD) The X-ray diffraction (XRD, X'PERT PRO from Philips, Netherlands) was evaluated to determine the crystal structure and phase the samples, with Cu-Kα radiation (λ=1.54178 Å), operated at 40 kV and 40 mA, was measured in 2θ range from 10 o to 80 o , performed on a University of Kashan (Iran). | 7 |
225723454 | Energy Dispersive X-Ray Analysis (EDS) The elemental composition of samples was studied by (EDS, MIRA3 TESCAN, Czech Republic) Figure 2A shows the XRD patterns of the PP pyrolysis at 1000ºC without catalyst and having the diffraction peaks at the value of 23º, 28.5º and 43º were ascribed to the (002), (100) and (101) reflections. Figure 2B shows the XRD patterns of the C 60 nanotubes from waste PP with MoO 3 , the diffraction peaks at the value of 23º, 28.5º and 43º were ascribed to the (002), (100) The other peaks notices refer to the additives of polymer and the substrate used in the measurement (17)(18) Average crystal size in the product that can be found using X-ray diffraction profile. Calculating the crystal size (D) can be done by using the Debye Scherrer equation: D = | 8 |
225723454 | Results and Discussion: Where is the Scherrer constant, λ is the wavelength of light used for the diffraction, β is the full width at half maximum of the sharp peaks and θ is the angle measured. The Scherrer constant ( ) in the above formula accounts for the shape of the particle and is generally taken to have the value 0.9 (19). From Table1, we could calculate the average crystal size of C 60 NTs as shown below: Average crystal size = 84.17 nm. The morphology of the sample was revealed by FESEM. Figure 3-A shows a typical FESEM image of the sample. It is found that large quantities of nanostructures (C 60 NTs) were obtained (12). These nanotubes are carbon (34.5-90.6) nm in diameter, and a few micrometers in length, as shown in Fig. 3 Figure 4 shows the high concentration of the carbon content which indicates high purity, and shows the amount of catalyst used in pyrolysis (20). The other elements noticed (Au, Si, Al and Cl) refer to the elements in standard in analysis device (21)(22), and the other components (K, Ca and Na) are additives to improve properties of polymer. | 9 |
102345223 | In today’s world, computer networks form an essential part of any organization. They are used not only to communicate information amongst the various parties involved but also to process data and store critical information which is accessible to approved subscribers. Protecting critical data, ensuring confidentiality, and thwarting illegal access are primary concerns for such organizations. This case study presents security recommendations for any such organization, to assist them in defining security policies at various levels of the network infrastructure. | 1 |
102345223 | Introduction In order to present the security considerations required in a corporate setup, we created a fictitious company by the name of MediSecure Corporation and tried to give it a real profile.The profile of MediSecure Corporation is as follows. MediSecure Corporation (referred to as our company or the company hereon) | 2 |
102345223 | Research Center Most pharmaceutical companies invest heavily in research, so they have advanced research facilities, which contain sensitive information that needs to be protected from data breach.Confidential data may include intellectual property pertaining to their on-going research, information about proprietary drugs, procedures regarding testing and trials and other procedures, all of which needs to be protected. | 4 |
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