Polar Aprotic Solvents Research Articles

New Insights into the Structure and Reactivity of Uracil Derivatives in Different Solvents-A Computational Study.

Ab initio calculations were carried out to understand the reactivity and stability of some uracil derivatives, cytosine, 1-methyl cytosine, and cytidine in solvents, water, dimethyl sulfoxide (DMSO), n-octanol, and chloroform. Geometries were fully optimized at MP2 and B3LYP using the 6-31+G(d,p) basis set by applying the Solvation Model on Density (SMD) in solvent systems. The syn conformer of cytidine (cytidine II) is the most stable conformer in the gas phase, while the anticonformer (cytidine IV) is most stable in all of the solvents. Solvation free energy and polarizability values in different solvents decrease in the order water > DMSO > n-octanol > chloroform, while dipole moment, first-order hyperpolarizability, and HOMO–LUMO energy gap values follow the order of polar protic solvent (water and n-octanol) > polar aprotic solvent (DMSO) > nonpolar solvent (chloroform). The solvation free energy, dipole moment, polarizability, and first-order hyperpolarizability values also follow the order of cytosine > 1-methyl cytosine > cytidine. To illustrate that the molecular properties correlate well with the reactivity of the molecules, ab initio calculations were carried out for the reaction of uracil derivatives with Br2 in the gas phase, water, DMSO, n-octanol, and chloroform. All ground and transition state geometries were fully optimized at B3LYP/6-31+G(d,p), and energies were also calculated at G3MP2 for cytosine and 1-methyl cytosine. For cytosine and 1-methyl cytosine, Gibbs energies of activation decrease with the polarity of the solvent that is chloroform > n-octanol > DMSO > water, while the Gibbs energies of activation for the reaction with cytidine decrease in the order of water > DMSO > n-octanol > chloroform. These results suggest that solvent polarity is very important for the stability and reactivity of uracil derivatives. Hydrogen bonding may also play an important role mainly for cytidine. Free energies of activation decrease with the size of the molecule, i.e., cytosine > 1-methyl cytosine > cytidine.

Photophysical property and thermal stability of a simple protonated hydrogen bonding complex: 3-Amino-5-nitro-[2,1]benzoisothiazole-p-toluenesulfonate

A straightforward reaction between 3-amino, 5-nitro [2,1] benzoisothiazole (ANB), and p-toluene sulfonic acid (PTSA) through a facile combination of individual ethanolic solutions resulted in a contemporary 1:1 protonated complex -3-amino, 5-nitro-benzoisothiazole-p-toluene sulfonate (ANBPTS). X-ray crystallography revealed proton transfer, connectivity of cationic and anionic species through hydrogen bonds and several short contacts leading to the stability and interesting material attributes. Acquired salt was characterized by various spectroscopic and microscopic techniques. Enhanced fluorescence was observed in polar aprotic solvents than in polar protic solvents and solid-state, good agreement with the observed greater lifetime in DMF solution. A large stokes shift was noticed in the range of 144 to 163 nm. Thermogravimetric analysis showed appreciable thermal stability of ~273 °C. The experimental optical band gap ~3.70 eV was compatible with the theoretical band gap calculated as 3.67 eV and 3.82 eV for the electronic transitions from SOMO to LUMO, due to two singly occupied molecular orbitals. Scanning electron microscopy images of the spin-coated and drop casted films showed microcrystalline structures of ~35 nm. Dynamic light scattering study (DLS) revealed ~300 nm-sized aggregates. However, the obtained compound showed poor antibacterial and antifungal activity when compared to the standard bacterial and fungal species.

Recycling gold from printed circuit boards gold-plated layer of waste mobile phones in “mild aqua regia” system

Traditional mechanical pretreatment and hydrometallurgy is the mainstream technology to recycle gold from waste printed circuit boards (PCBs). However, this method is cumbersome and often employs toxic/harsh chemicals. In the present study, gold was easily recycled from PCBs gold-plated layer of waste mobile phones (WMPs) in DMF-CuCl2-CaCl2 (DMF: dimethyl formamide) system what we call “mild aqua regia” without pretreatments or enrichment process, and the reaction system could be cyclic utilized. In such reaction system, gold could be recycled through leaching, precipitation and filtration. The reaction parameter optimization and reaction mechanisms were studied. Under the optimized conditions, the gold leaching rate and precipitation rate could reach over 99%. DMF plays a significant role in the leaching system. As a typical polar aprotic solvent, DMF cannot solvate Cl−. Thus, “Cl−” exists in a “naked state”, and it can easily react with Au. Besides, Au (III) could generate a complex through the complexation with DMF which could result in the redox potentials reduce and move the equilibrium to the Au leaching side. In summary, this study provided a fundamental basis as well as practical guidance for recovering precious metals from waste electrical and electronic equipment in an efficient manner.

Standard Electrode Potentials for Electrochemical Hydrogen Production, Carbon Dioxide Reduction, and Oxygen Reduction Reactions in N,N-Dimethylacetamide

Four standard electrode potentials versus the standard hydrogen electrode (SHE) are reported in a polar aprotic solvent, N,N-dimethylacetamide (DMA) at 298 K: (1) −0.319 ± 0.033 V for a H2 production; (2) −0.415 ± 0.033 V and −1.195 ± 0.033 V for CO2 reductions to produce carbon monoxide (CO) in the absence and presence of water, respectively; and (3) +0.918 ± 0.033 V for an O2 reduction (ORR) or O2 evolution (OER) reactions. These potentials were estimated based on measurements of absolute (and conventional) acidity constants for several Brønsted acids in DMA including CO2 with water ([H2O] = 1.1 M) of which absolute pKa is 18.6 ± 0.2 in reference to aqueous proton at standard states. The standard Gibbs transfer energy of proton was calculated to be −31 ± 3 kJ/mol from water to DMA at 298 K.

Synthesis and Characterization of New Organosoluble and Thermally Stable Aromatic Polyamides Containing Flexible Ether, Ketone, and Methylene Linkages

AbstractA new aromatic diacid monomer, namely, 1,4‐phenylene‐bis‐[[4′‐(4″‐carboxy methylene) phenoxy phenyl] methanone] (PBCPPM) is successfully synthesized and characterized by physical constant, FT‐IR, NMR (1H and 13C) spectroscopy, and mass spectrometry. Synthesis of new series of polyamides with high thermal stability and improved solubility are performed by Yamazaki's direct phosphorylative polycondensation method from new PBCPPM with different aromatic diamines. The inherent viscosity of these polyamides is in the range 0.47–0.81 dL g−1. All these polyamides are amorphous or partly crystalline and reveal good solubility in polar aprotic solvents and exhibit glass transition temperatures between 201 and 232 °C. Initial decomposition temperatures are in the range 300–367 °C and T10 is in the range of 376–414 °C indicating good thermal stability of these polyamides. The present observations suggest that these polyamides can find potential applications as high performance polymers.

Tri-functional oligomeric polyesters prepared from new dicarboxylic acids containing several amino acids residues by Higashi methodology: synthesis, characterization, and study of solubility and thermal behavior

The synthesis of polyfunctional aliphatic oligomeric polyesters (poly(ether-imido-esters; PEIEs) containing several amino acid residues is described, and their thermal properties and solubility behavior were studied. The new symmetrical monomeric dicarboxylic acids were synthesized using 4-nitrophthalonitrile as starting material, which reacted with bisphenol-A or bis(4-hydroxyphenyl)diphenylmethane. Then, the tetranitrile derivatives were hydrolyzed to the tetracarboxylic acids and dehydrated to the respective dianhydrides. Finally, these compounds reacted with the amino acids glycine or L-alanine to obtain the aliphatic dicarboxylic acid monomers. PEIEs were obtained by Higashi methodology from these monomers and bisphenol-A, characterized by elemental analysis, NMR and IR, and the results were in agreement with the structures. The materials were soluble at 25 °C in several aprotic polar organic solvents and some in CHCl3 and THF. In agreement with the viscosity and SEC results, PEIEs were oligomers with degree of polymerization of four and six, and Mw and Mn between 7370–9790 g/mol and 3680–4850 g/mol, respectively. The samples showed low Tg values (124–160 °C), associated with important structural flexibility promotes by dicarboxylic acid monomers. Despite this, this parameter depended of the aminoacidic residue nature in the sense that when the volume of it increased, the Tg also increased due to a decrease in the free rotation that negatively affects the segmental movements of the chains. This effect was also observed when the side groups of the diphenol moiety of the dicarboxylic acid monomers increase from methyl to phenyl. The recorded TDT10% values from the TGA analysis (334–457 °C) do not allow to consider these samples as thermoset materials. In this sense, it was possible to observe an average increase of 8–13 °C and 23–28 °C when the lateral group volume of the amino acid residues and of the diphenol moiety are increased, respectively.

Highly Stable Membranes of Poly(phenylene sulfide benzimidazole) Cross-Linked with Polyhedral Oligomeric Silsesquioxanes for High-Temperature Proton Transport

Poly(phenylene sulfide benzimidazole) has been synthesized and tested as a potential material for high-temperature proton transport. A high content of sulfide bonds has been implemented in the polymer chains to endow a high antioxidant capacity and, in combination with bulky benzimidazole pendant units, to significantly suppress crystallinity and thereby improve the solubility in highly polar aprotic solvents. The amorphous polymer has high thermal stability and high glass transition temperature (Tg). Freestanding, insoluble, and robust membranes were obtained via thermal cross-linking of the benzimidazole moieties with octa-glycidyl polyhedral oligomeric silsesquioxane (g-POSS). The series of hybrid networks (cPPSBi_X, with X being the g-POSS content wt %) showed excellent oxidative stability, with cPPSBi_15 having weight loss lower than 5% after 264 h in Fenton’s reagent at 80 °C. Elastic moduli as high as 868 MPa with reduced strain at break (1.8%) were obtained. After doping the membranes with phosphoric acid, proton conductivity in the range of 2.3 × 10–2 S cm–1 at 180 °C was obtained, and the membranes show a stress at break of 2.3 MPa. Dimensional and mechanical stability were maintained also at high doping levels thanks to the inclusion of g-POSS which provides the resulting hybrid networks with increased free volume and high cross-link density.

A multireference configuration interaction study with singles and doubles of some mesoionic rings: reaction and activation free energies for the ring‐opening reaction

AbstractFor the first time, multireference configuration interaction with singles and doubles (MR‐CISD) calculations (including extensivity corrections, MR‐CISD+Q) have been performed to study the ring‐opening reactions of the following mesoionic rings and their 2, 3, and 4 methyl‐substituted derivatives: (a) 1,3‐oxazol‐5‐one, (c) 1,3‐oxazol‐5‐thiolate, and (d) 1,3‐thiazol‐5‐thiolate. The ring‐opening reaction of the parent 1,3‐thiazol‐5‐one mesoionic ring (b) has also been studied. The effect of methyl and S replacement on the reaction and activation free energies (ΔG and ΔG†, respectively) is studied. For a, the effect of methyl replacement on C2 is almost negligible, while on N3 and C4, it is significantly larger, especially in the latter position. The open structure (ketene form) of a is considerably more stable, and the replacement of the exocyclic O by S stabilizes the ketene tautomer even more and increases ΔG† considerably. On the other hand, replacement of the endocyclic O by S (yielding b) completely prevents the formation of the open structure, while replacement of both endo and exo atoms strongly stabilizes the cyclic structure and leads to a remarkably high value of ΔG†. In some cases, the relative polarity of the stationary points is used to estimate how ΔG and ΔG† are expected to change as one goes from the gas phase to aprotic polar solvents. A linear correlation between the multiconfigurational character of the mesoionic rings and ΔG† has been observed, and such correlation is used to estimate the ΔG† values for the methyl‐substituted c and d. The largest barrier (13.78 kcal/mol) has been obtained for the 4‐methyl‐1,3‐thiazol‐5‐thiolate (4‐m‐d).

Magnetic tetraethylenepentamine-functionalized graphene oxide to prepare new methyl rich bisphenol-based soluble and heat-resistant polyamide ether nanocomposites: Synthesis and characterization

The new magnetic and heat-resistant polyamide ether (PAE)/graphene oxide (GO) nanocomposites were prepared by blending PAE with modified GO. Furthermore, a novel PAE containing flexible ether, methyl, and triphenylmethane moiety in the main chain of PAE was prepared by direct polycondensation reaction of a diamine and 4,4′-(butane-1,4-diylbis(oxy))dibenzoic acid (9). The prepared PAE was characterized using various techniques. The obtained PAEs were readily soluble in various aprotic polar solvents at room temperature. The incorporation of bulky aryl pendant groups and flexible ether linkage into the backbones of polyamide may provide beneficial effects for solubility, as this approach produces a separate chain of the polymer, which makes weaker of hydrogen bonds. GO, which synthesized by the Hummer method, was modified with tetraethylenepentamine (GO-TEPA) and sequentially magnetized with Fe3O4 nanoparticles via chemical coprecipitation (GO-TEPA@Fe3O4). The PAE/GO/TEPA@Fe3O4 nanocomposite films, PAE/GO-TEPA@Fe3O4, were also synthesized as a heat-resistant and superparamagnetic nanocomposites, which were characterized using different analyses, such as field emission scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray, thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and Fourier transform infrared techniques. TGA of nanocomposites exhibit higher degradation temperature than that of neat PAE, which is an indication of high levels of interfacial interaction and dispersion.

Bulky-substituted phthalodinitriles and cobalt and copper phthalocyanines based on them: synthesis, thermal analysis and spectroscopic properties

By the nucleophilic substitution of the nitro group in 4-nitrophthalononitrile for the residues of alkoxy-substituted phenols, the synthesis of alkoxyphenoxyphthalonitriles was carried out. By template condensation of the substituted phthalonitriles obtained with copper and cobalt acetates at 200 °C, the corresponding phthalocyaninates were obtained. The conditions for the isolation and purification of the complexes synthesized were selected. The stability of substituted phthalonitriles and phthalocyaninates synthesized based on them regarding to heating in an argon–oxygen medium was evaluated (1:1 ratio). It was found the compounds obtained are thermally stable, and the destruction of phthalocyanines begins at lower temperatures compared to the corresponding phthalonitriles. For the complexes synthesized, the spectroscopic properties in organic solvents and concentrated sulfuric acid were studied. The influence of the nature of the substituent, metal complexing agent and solvent on the nature of the spectroscopic curves and the position of the main absorption band of phthalocyanine complexes has been established. It is noted passing from polar aprotic solvents to nonpolar ones, a shift of the maximum of the Q absorption band for the studied macrocycles was observed. Electronic absorption spectra in sulfuric acid show a significant bathochromic shift of the absorption band. An increase in the length of the alkyl substituent practically was found not to affect the position of the absorption maximum. Passing from complexes with Co(II) to Cu(II), a bathochromic shift of the absorption maximum was observed.

Organic solvent nanofiltration membrane with improved permeability by in-situ growth of metal-organic frameworks interlayer on the surface of polyimide substrate

Organic solvent nanofiltration (OSN) has a good application prospect in the field of organic solvent separation, but low organic solvent permeance is the main obstacle restricting its application. This work reports a thin film composite (TFC) nanofiltration membrane prepared by interfacial polymerization (IP) on the HKUST-1 MOF interlayer grown in situ on a crosslinked polyimide (PI) substrate. The MOF interlayer improves the hydrophilicity and porosity of the support membrane. In addition, the MOF interlayer controls the diffusion of piperazine (PIP) during the IP process, which induced to form a thin and highly crosslinked polyamide (PA) separation layer. The increased effective membrane area and the reduced thickness of PA separation layer resulted in a methanol permeation flux up to 9.59 L·m−2·h−1·bar−1, while maintaining the rejection of the negatively charged Brilliant Blue G 250 dye (MW = 858.05 g·mol−1) at 98.8%. Furthermore, the stability of the TFC membranes in polar aprotic solvents such as N, N-dimethylformamide highlights their potential for OSN applications in chemical industries.

A comprehensive experimental study on the production of key platform chemicals from raw biomass

In recent years, the utilization of biomass resources in the production of industrial chemicals and fuels become more preferable when considering low cost, renewability and environmental concerns. In this study, 5-hydroxymethylfurfural and levulinic acid obtained from catalytic one-pot reaction of different feedstocks (microcrystalline cellulose, corn straw, sorghum and waste fluff) under the specified conditions (temperature, time, solvent ratio, catalyst loading) using different cosolvents (methanol, hexane, tetrahydrofuran (THF), acetone) in reaction medium. Over the Amberlyst-15 catalyst, significant increase in levulinic acid concentration was achieved using acetone as cosolvent thus 94.34 ± 5.25 mg levulinic acid was obtained from 1 g sorghum at 180 °C for 30 min. The use of polar aprotic solvents such as THF and acetone promoted further hydrolysis of raw biomass materials in reaction medium.

Selective and Efficient Production of Biomass-Derived Vinylfurans

We describe a two-step catalytic process for the selective and rapid conversion of biomass-derived acetylfurans into vinylfurans. This is accomplished by nearly quantitatively reducing acetylfurans into furyl alcohols using a copper chromite catalyst and exploiting the promoter-like properties of ethanol, the solvent. Subsequently, furyl alcohol is dehydrated using solid-acid catalysts. Catalyst deactivation due to oligomeric species is a major issue, but the activity can be partially recovered by calcination. Optimization of reaction conditions showed that the selectivity could be increased by using nitrobenzene, a polar aprotic solvent. The high-boiling point solvent allows the formation of vinylfurans with a selectivity of up to 85%; the product can be isolated in high purity by distillation.

The pharmaceutical solvent N-methyl-2-pyrollidone (NMP) attenuates inflammation through Kr\xfcppel-like factor 2 activation to reduce atherogenesis

N-methyl-2-pyrrolidone (NMP) is a versatile water-miscible polar aprotic solvent. It is used as a drug solubilizer and penetration enhancer in human and animal, yet its bioactivity properties remain elusive. Here, we report that NMP is a bioactive anti-inflammatory compound well tolerated in vivo, that shows efficacy in reducing disease in a mouse model of atherosclerosis. Mechanistically, NMP increases the expression of the transcription factor Kruppel-like factor 2 (KLF2). Monocytes and endothelial cells treated with NMP express increased levels of KLF2, produce less pro-inflammatory cytokines and adhesion molecules. We found that NMP attenuates monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha (TNF-α) by reducing expression of adhesion molecules. We further show using KLF2 shRNA that the inhibitory effect of NMP on endothelial inflammation and subsequent monocyte adhesion is KLF2 dependent. Enhancing KLF2 expression and activity improves endothelial function, controls multiple genes critical for inflammation, and prevents atherosclerosis. Our findings demonstrate a consistent effect of NMP upon KLF2 activation and inflammation, biological processes central to atherogenesis. Our data suggest that inclusion of bioactive solvent NMP in pharmaceutical compositions to treat inflammatory disorders might be beneficial and safe, in particular to treat diseases of the vascular system, such as atherosclerosis.

Synthesis, crystal structure, hirshfeld surface analysis, spectroscopic, biological and first-principles studies of novel aminocoumarins

Two novel aminocoumarins 3-(1-(2 aminophenylamino) ethylidene)chromene-2,4‑dione, noted (1) and 3-(1-(2–1-(2, 4-dioxochromene-3-ylidene) ethylamino)phenylamino) ethylidene) chromene -2,4‑dione,noted (2), were synthesized from 3-acetyl-4-hydroxycoumarin and ortho-phenylenediamine in absolute ethanol and characterized by spectroscopies methods (FT-IR, UV–vis and fluorescence). The crystal structures of the mentioned compounds were solved from single-crystal diffraction data at low temperature. The compound (1) crystallizes in the orthorhombic system with space group Iba2 while (2) is monoclinic with space group P21/c. Hirshfeld surface analysis indicates the presence of the π-π stacking in the aminocoumarin structures with the contribution of 7.8% for (1) and 8.7% for (2) of the total Hirshfeld area. The optimized DFT geometries (B3PW91/6–311 G (2df, p)) and the spectral simulations agree well with the experimental data. Theoretical reactivity behavior was assessed, taking into account HOMO-LUMO diagrams and Molecular Electrostatic Potential maps. The two aminocoumarins derivatives have fluorescence properties. Analysis of the photoluminescence spectra shows that the emission intensity is high for the solutions of the two compounds in polar aprotic solvents (DMSO, DMF). The aminocoumarins were monitored for antimicrobial activity using the disk diffusion method. The coumarin (1) is effective against S. aureus (gram-positive bacteria) and S. typhy (gram-negative bacteria), but the coumarin (2) showed markedly weak antibacterial activity.

Hydroxy-benzimidazoles as blue-green emitters: Synthesis, structural and DFT studies

The new benzimidazole ligands (3a-e) were synthesized using ethyl 4-(butylamino)-3-nitrobenzoate and substituted salicylaldehyde in the presence of sodium dithionite reagent which undergoes “one-pot’’ nitro reductive cyclization. Here benzimidazole moiety acts as an electron-acceptor (A) whereas substituted 2-hydroxyphenyl moiety acts as an electron-donor (D) unit. The molecular structures were characterised by FTIR, 1H NMR, 13C NMR, single crystal XRD and MS analysis. Optoelectronic properties were determined by UV–vis, solution and solid photoluminescence, quantum yield and lifetime. The solvent-dependent absorption and emission were studied using both polar protic and polar aprotic solvents. All the derivatives exhibited ESIPT, especially compound ethyl 1-butyl-2-(3,5-dichloro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (3e) displayed dual emission in both polar protic and polar aprotic solvents. The compound stability and electrochemical property were determined by thermal gravimetric analysis (TGA) and cyclic voltammetry (CV) respectively. The compounds emit intense blue-green fluorescence with high to moderate quantum yield. Also, these derivatives exhibited a high Stokes shift. The computational studies like Density-Functional Theory (DFT) and Molecular Electrostatic Potential (MEP) were conducted to provide important insights into the structure-property relationships. The crystal packing is stabilized through intermolecular hydrogen bonds (C---H…O) and intermolecular interactions (π… π). The findings of results help in developing novel ligands in the field of organic optoelectronics.

New Poly(imide)s Bearing Alkyl Side-Chains: A Study on the Impact of Size and Shape of Lateral Groups on Thermal, Mechanical, and Gas Transport Properties.

A set of five new aromatic poly(imide)s (PIs) incorporating pendant acyclic alkyl moieties were synthesized. The difference among them was the length and bulkiness of the pendant group, which comprises of linear alkyl chains from three to six carbon atoms, and a tert-butyl moiety. The effect of the side group length on the physical, thermal, mechanical, and gas transport properties was analyzed. All PIs exhibited low to moderate molecular weights (Mn ranged between 27.930–58.970 Da, and Mw ranged between 41.760–81.310 Da), good solubility in aprotic polar solvents, except for PI-t-4, which had a tert-butyl moiety and was soluble even in chloroform. This behaviour was probably due to the most significant bulkiness of the side group that increased the interchain distance, which was corroborated by the X-ray technique (PI-t-4 showed two d-spacing values: 5.1 and 14.3 Å). Pure gas permeabilities for several gases were reported (PI-3 (Barrer): He(52); H2(46); O2(5.4); N2(1.2); CH4(1.1); CO2(23); PI-t-4 (Barrer): He(139); H2(136); O2(16.7); N2(3.3); CH4(2.3); CO2(75); PI-5 (Barrer): He(44); H2(42); O2(5.9); N2(1.4); CH4(1.2); CO2(27); PI-6 (Barrer): He(45); H2(43); O2(6.7); N2(1.7); CH4(1.7); CO2(32)). Consistent higher volume in the side group was shown to yield the highest gas permeability. All poly(imide)s exhibited high thermal stability with 10% weight loss degradation temperature between 448–468 °C and glass transition temperature between 240–270 °C. The values associated to the tensile strength (45–87 MPa), elongation at break (3.2–11.98%), and tensile modulus (1.43–2.19 GPa) were those expected for aromatic poly(imide)s.

A DFT investigation on aromatic nucleophilic substitution (SNAr) reaction between 4-fluoro-1-naphthaldehyde/4-fluoro-2-naphthaldehyde/1-fluoro-2-naphthaldehyde/1-fluoronaphthalene and methylthiolate ion in gas phase and in protic/aprotic solvents

We have investigated the mechanism of aromatic nucleophilic substitution (SNAr) reaction between 4-fluoro-1-naphthaldehyde/4-fluoro-2-naphthaldehyde/1-fluoro-2-naphthaldehyde/1-fluoronaphthalene with methylthiolate by DFT calculations at B3LYP/6–31+G (d,p) level of theory in gas phase and also in polar protic/aprotic solvents. The results show that aromatic nucleophilic substitution reaction proceeds by concerted mechanism via formation of single transition state as it has lower activation energy barrier as compared with stepwise mechanism. The introduction of solvent increases the activation energy barrier indicating significant effect of solvents on transition state. The activation energy barrier was found to be a minimum in gas phase then in DMSO which is followed by protic polar solvents methanol and water. Thus, the polar aprotic solvent DMSO works best for aromatic nucleophilic substitution of fluorine. The presence of a formyl group was found to be essential for reaction to take place, and in the gas phase as well as in solution phase, the order of reactivity was found to be 4-fluoro-1-naphthaldehyde > 1-fluoro-2-naphthaldehyde > 4-fluoro-2-naphthaldehyde > 1-fluoronaphthalene.

Predictability of drug encapsulation and release from propylene carbonate/PLGA microparticles.

Key parameters for microparticle-based parenteral depot formulation development are entrapment efficiency and sustained drug release, which both depend on the intermolecular affinity of the components. Here, partial solubility parameters were evaluated as descriptors for 21 drug substances and 3 polymers in propylene carbonate (PC). Out of these 21 drug substances, eight BCS class II substances (celecoxib, clotrimazole, erythromycin, ibuprofen, indomethacin, itraconazole, lopinavir and ritonavir) were encapsulated using PLGA (Poly(DL-lactide-co-glycolide)) as polymer matrix and PC as a polar aprotic solvent in order to assign microparticle properties to potential affinity-related interactions using partial solubility parameters. Microparticle morphology was highly dependant on the specific glass transition temperature (Tg) of the encapsulated drug substance. A strong correlation (R=0.912) between the encapsulation efficiency and the difference in total solubility parameter (Δδt API-PLGA) underlined the encapsulation predictability. Moreover, in drug release, a significant impact of Δδt API-PLGA on initial burst was observed and even more pronounced on the release rate of the encapsulated drug substance. The possibility to predict these important microparticle properties underline the value of including solubility descriptors such as partial solubility parameters into microparticle formulation development.

Flexible Aliphatic-Aromatic Polyamide Thin Film Composite Membrane for Highly Efficient Organic Solvent Nanofiltration.

Membranes with strong solvent resistance and efficient molecular separation are desirable in industries. Especially the fractionation of organic molecules in harsh organic solvents still remains a challenge in the pharmaceutical industry. Here, we report a flexible aliphatic-aromatic polyamide thin-film composite (TFC) membrane with high stability, permeability, and precise selectivity in mild solvents as well as in polar aprotic solvents. This composite organic solvent nanofiltration (OSN) membrane integrates a cross-linked sub-100 nm nanofilm and a nanofibrous sublayer. The flexible aliphatic chains in the polyamide network render the selective layer with a tunable free volume in different organic solvents. Consistent with the solvent swelling degrees, the membrane shows a cutoff in a sequence of dimethyl sulfoxide (DMSO, MWCO: 814 g mol-1) > N,N-dimethylformamide (DMF, MWCO: 648 g mol-1) > methanol (MWCO: 506 g mol-1, with DMF activation) > methanol (MWCO: 327 g mol-1). The membrane can precisely fractionate two molecules with difference in molar mass of <166 g mol-1 in a polar aprotic solvent, DMSO. Long-term filtration tests in DMF further demonstrate that the TFC membrane has an outstanding chemical stability and molecular selectivity in aggressive organic media. This work provides an efficient way to control OSN membrane separations by introducing flexible alkane chains into the rigid polymer structure followed by solvent activation. Additionally, the high permeance and excellent separation efficiency of the TFC membrane highlight its great potential for molecular separation in pharmaceutical and chemical industries.