Showing papers on "Solvent published in 1991"

Protein--solvent interactions in pharmaceutical formulations.

Abstract: The stability of proteins is affected by a variety of solvent additives. Sugars, certain amino acids and salts, and polyhydric alcohols stabilize proteins in solution and during freeze-thawing. Urea and guanidine hydrochloride destabilize proteins under either condition. These effects can be explained from the preferential interactions of the cosolvents with the proteins; i.e., the protein stabilizers are preferentially excluded from the proteins, while the destabilizers bind to them. There is a class of compounds, such as polyethylene glycol and 2-methyl-2,4-pentanediol, that destabilize proteins at high temperature but stabilize them during freeze-thawing. Such effects can be accounted for by their preferential exclusion from the native proteins determined at room temperature and from their hydrophobic character, which depends on temperature. During freeze-drying, only a few sugars appear to be effective in protecting proteins from inactivation, as most other stabilizers cannot exert their action on proteins without water. The stabilization is due to hydrogen bonding between the sugars and the dried proteins, the sugars acting as water substitute. Understanding the mechanism of the effects of solvent additives on the protein stability should aid in the development of a suitable formulation for protein.

Solvent selection strategies for extractive biocatalysis.

Abstract: This report follows the development of systematic solvent screening strategies for the identification of superior pure solvents and introduces techniques for the identification of effective coextractants. Specifically, methods to predict the biocompatibility and extractant capability of solvents are discussed. Biocompatibility is predicted by using heuristic data or the correlations between bioactivity and the logarithm of the partition coefficient of the solvent or the concentration of solvent in the cell membrane. A computer program, known as the extractant screening program or ESP, has been developed to effectively predict the behavior of virtually any product in any solvent/aqueous system. It is demonstrated that a biocompatible yet poor solvent can be mixed with a toxic solvent that has better extractant properties to yield a mixture with improved solvent characteristics that is still biocompatible. The fact that solvents do not mix in an ideal manner is exploited by using ESP to identify solvent mixtures that are still biocompatible at relatively high concentrations of toxic solvent.

Synthesis and characterization of polymers produced by horseradish peroxidase in dioxane

Abstract: Polymers were synthesized from substituted phenolic and aromatic amine compounds with hydrogen peroxide as the source of an oxidizing agent and horseradish peroxidase enzyme as the catalyst. The polymerization reaction was carried out in a monophasic organic solvent with small amounts of water at room temperature. Conditions for the synthesis of polymers with respect to reaction time and yield were studied with a number of monomers at different concentrations and in solvents with different buffers with pH range of 5.0–7.5. Physical and chemical properties of these homo-and copolymers were determined with respect to melting point, solubility, elemental analysis, molecular weight distribution, infrared absorption (including FTIR), solid-state 13C nuclear magnetic resonance, thermal gravimetric analysis, and differential scanning calorimetry. The enzyme catalyzed reactions produced polymers of molecular weight greater than 400,000 which were further fractionated by differential solubility in solvent mixtures and the molecular weight distribution of the polymer fractions were determined. In general, the polymers synthesized have low solubilities, high melting points, and some degree of branching.

Potential of mean force by constrained molecular dynamics: A sodium chloride ion-pair in water

Abstract: The constrained molecular dynamics simulation method has been used to obtain the mean force and the mean force potential between two particles in solution. The method has been tested for a Lennard-Jones liquid and applied to the study of a Na+-Cl− ion-pair in aqueous solution. A flexible SPC model for water has been assumed. The results have been interpreted in the light of the solvent structure around the ions for separations corresponding to the maxima and minima of the mean force potential. In contrast to earlier studies using rigid water models, the solvent separated ion pair configurations are more stable than the contact ion pair configurations.

High frequency permittivity and its use in the investigation of solution properties

Abstract: Recent results from permittivity measurements at microwave to far-infrared frequencies are reported for various liquid electrolyte and non-electrolyte systems. They enlarge our knowledge on processes which produce (by their complex interplay of orientational, intramolecular, kinetic, H-bonding, diffusional and migrational modes) the properties of pure solvents, solvent mixtures and solutions. Protic solvents show three relaxational processes: re-establishment of t he perturbed solvent structure, "intramolecular" rotation of solvent molecules as monomers and in H-bonded chains or networks, and very short relaxa- tion times of about 1 ps due to H-bond dynamics. Aprotic solvents display a more or less continuous relaxation time distribution. Solvent mixtures show a particular behaviour related to the properties of their constituents. The addition of salt affects the relaxation times of t he solvents, but no new modes are generated by free ions. In contrast, ion pairs and other solute complexes act as dipoles and display specific relaxation processes.

Solvent effects on biocatalysis in organic systems: equilibrium position and rates of lipase catalyzed esterification.

Abstract: Porcine pancreatic lipase immobilized on celite particles has been employed as a catalyst for the esterification of dodecanol and decanoic acid in a predominantly organic system. Solvent influence on the equilibrium position and on the catalyst activity has been studied using 20 solvents, including aliphatic and aromatic hydrocarbons, ethers, ketones, nitro- and halogenated hydrocarbons, and esters. The equilibrium constant for esterification correlates well with the solubility of water in the organic solvent, which in turn shows a good relationship with a function of Guttman's donor number and the electron pair acceptance index number of the solvent. This may be rationalized in terms of the requirements for solvation of water and of the reactants. The catalyst activity, measured as the initial rate of the esterification reaction, is best correlated as a function of both n-octanol-water partition coefficient (log P) and either the electron pair acceptance index or the polarizability.

Microscopic calculations of solvent effects on absorption spectra of conjugated molecules

Abstract: Microscopic approaches for calculating absorption spectra of molecules in solutions are developed and examined. These methods evaluate self-consistently the relationship between the solute and solvent polarization, incorporating the potential from the permanent and induced solvent dipoles in the solute Hamiltonian. Two microscopic solvent models are examined in the framework of the present formulation. The first one is the simplified Langevin dipoles (LD) solvent model, which provides fast and reliable estimates of solvent effects on absorption spectra. The second involves an all-atom solvent model and molecular dynamics simulations of the fluctuations of the solvent and the solute

Oral compositions of proteinaceous medicaments

Abstract: Proteinaceous medicaments such as erythropoetin, insulin and calcitonin are formulated in a medium comprising a polyol pharmaceutical solvent combined as co-solvent with a lipid pharmaceutical solvent. The formulation is adapted for oral administration as a liquid as well as a filled hard or soft gelatin capsule. The preferred polyol solvent is polyethylene glycol/propylene glycol; the preferred lipid solvent is oleic acid.

α‐Methylidene‐ and α‐Alkylidene‐β‐lactams from Nonproteinogenic Amino Acids

Abstract: Treatment of methyl 2-(1-hydroxyalkyl)prop-2-enoates 1 with conc. HBr solution afforded methyl (Z)-2-(bromomethyl)alk-2-enoates 2, which were transformed regioselectively into N-substituted methyl (E)-2- (aminomethyl)alk-2-enoates 3 (SN2 reaction) and into N-substituted methyl 2-(1-aminoalkyl)prop-2-enoates 4(SN2′ reaction). Regiocontrol of nucleophilic attack by amine was accomplished simply by choice of solvent, the SN2 reaction occurring in MeCN and the SN2′ reaction in petroleum ether. Hydrolysis and lactamization afforded β-lactams 7 and 8, containing an exocyciic alkylidene and methylidene group at C(3), respectively.

Immobilized Metal Ion Affinity Chromatography (IMAC) Chemistry and Bioseparation Applications

Abstract: This review discusses the principles of immobilized metal ion affinity chromatography (IMAC) and its applications to protein separations. IMAC functions by binding the accessible electron-donating pendant groups of a protein - such as histidine, cysteine, and tryptophan - to a metal ion which is held by a chelating group covalently attached on a stationary support. A common chelating group is iminodiacetate. The ions commonly used are of borderline or soft metals, such as Cu2+, Ni2+, Co2+, and Zn2+. Protein retention in IMAC depends on the number and type of pendant groups which can interact with the metal. The interaction is affected by a variety of independent variables such as pH, temperature, solvent type, salt type, salt concentration, nature of immobilized metal and chelate, ligand density, and protein size. Proteins are usually eluted by a decreasing pH gradient or by an increasing gradient of a competitive agent, such as imidazole, in a buffer. There are still several unresolved issues in...

7-Azaindole in alcohols: solvation dynamics and proton transfer

Abstract: The photoinduced excited-state double proton-transfer reaction of 7-azaindole has been examined in a variety of alcohol solvents. The influence of temperature and solvent deuteration has been investigated.

Continuous acetone-butanol-ethanol (ABE) fermentation using immobilized cells of Clostridium acetobutylicum in a packed bed reactor and integration with product removal by pervaporation.

Abstract: An integrated solvent (ABE) fermentation and product removal process was investigated. A stable solvent productivity of 3.5 g/L h was achieved by using cells of Clostridium acetobutylicum immobilized onto a packed bed of bonechar, coupled with continuous product removal by pervaporation. Using a concentrated feed solution containing lactose at 130g/L, a lactose value of 97.9% was observed. The integrated fermentation and product removal system, with recycling of the treated fermentor effluent containing only low amount of solvents (/but lactose and acids), leads to only low acid losses. Therefore, most of the acids are converted to solvents, and this results in a high solvent yield of 0.39 g solvents/g lactose utilized. The pervaporation system provided a high product removal rate even at low solvent concentrations. A solvent membrane flux of 7.1 g/m(2) h with a selectivity of 5 was achieved during these investigations. The system proved to be very reliable.

Time-resolved fluorescence of nitrobenzoxadiazole-aminohexanoic acid: effect of intermolecular hydrogen-bonding on non-radiative decay.

Abstract: The fluorescence kinetics of the nitrobenzoxadiazole (NBD) chromophore were studied at low concentrations in solvents with varying polarity and hydrogen-bonding donor strength. The emission decay was essentially single exponential in all solvents studied. While the absorption and fluorescence solvatochromism is determined largely by the solvent polarity, the S1 state decay kinetics are strongly modulated by the solvent H-bonding capacity. The NBD emission lifetime, generally approximately 7-10 ns in the aprotic solvents, is reduced to 0.933 ns in water. The solvent deuterium isotope effect on the fluorescence decay is substantial in D2O and in methanol-d4, but is insignificant in DMSO-d6. These results are consistent with acceleration of S1----S0 internal conversion through an accepting vibrational mode created by intermolecular hydrogen-bonding of the NBD chromophore to an H atom-donating solvent. This work bears on the practically of using NBD as a fluorophore in assays for estrogen and progesterone receptors.

Solubility of o-hydroxybenzoic acid in supercritical carbon dioxide

Abstract: The experimental equilibrium solubilities of o-hydroxybenzoic acid in supercritical carbon dioxide were measured at temperatures between 35 and 55 o C and for pressures from 80 to 205 bar. Negligible solubility of m- and p-hydroxybenzoic acid was observed over the same range of temperature and pressure investigated. The solubility data was correlated by use of the thermodynamic model relating the solubility to the solvent density, an empirical model relating the enhancement factor to the density of the solvent, and a semiempirical correlation, based partly on regular solution theory and the van der Waals equation of state

Analysis of Solvent Effects on the Menshutkin Reaction

Abstract: The reaction between ammonia and methyl bromide, which has been taken as a model for the Menshutkin reaction, has been studied through ab initio methods in the gas phase and in solution using discrete and continuum representations of the solvent. The solvent effect on this reaction bears a resemblance with other sN2 reactions but also exhibits some differences with them. The main results turn out to be, on one hand, a decrease in the energy barrier upon increase in solvent polarity, and, on the other hand, the transition state is found earlier along the reaction coordinate., showing .the participation of solvent parameters in the reaction coordinate. The polarization of the solute by the reaction field created by the solvent polarization is one of the most important aspects of the coupling between the solvent and the chemical system. This translates into an increase of the weight of the charge-transfer configuration with respect to the weight in the gas phase. Likewise, fluctuations increasing the reaction field are stabilized by instantaneous changes in the electronic distribution of the solute.

Reactivities of triarylmethyl and diarylmethyl cations with azide ion investigated by laser flash photolysis. Diffusion-controlled reactions

Abstract: By use of the technique of laser flash photolysis, rate constants k AZ and k S have been directly measured for the reactions at 20 o C in acetonitrile-water (AN-W) solutions of varying composition of 18 triarylmethyl and 10 diarylmethyl cations with azide and solvent. The cations have k S that depend on substituent and vary from ∼10 1 to ∼10 7 s −1 . For the more stable ions k AZ also varies, increasing with decreased electron donation and also increasing by as much as 10 3 with increasing acetonitrile content. For less stable cations, however, the rate constant becomes independent of substituent

Thermal decomposition of nitrate esters

Abstract: Rates of thermal decompositin and solvent rate effects have been measured for a series of nitrate esters. The alkoxy radicals formed by homolysis together with some of their further degradation products have been stabilized by hydrogen donation. Internal and external return of nitrogen dioxide have been demonstrated by solvent cage effects and isotope exchange. Radical-stabilizeing substituents favor β-scission. Dinitrates in a 1,5 relationship behave as isolated mononitrates. Dinitrates in a 1,3 or 1,4 relationship exhibit intramolecular reactions. Tertiary nitrate esters in diethyl ether undergo elimination rather than homolyisis

Picosecond measurements of phenol excited‐state proton transfer in clusters. I. Solvent basicity and cluster size effects

Abstract: Excited‐state proton transfer (ESPT) rates in molecular clusters were measured as a function of cluster size using picosecond spectroscopy in a molecular beam mass spectrometer. ESPT from the S1 state of phenol to base solvent clusters (NH3)n occurs for a critical solvent cluster size n≥5, with a rate constant of k=(60±10 ps)−1 for n=5–7. ESPT showing critical cluster‐size dependencies was also observed in the basic solvent N(CH3)3(n≂3). Proton transfer was not observed in the less‐basic solvent clusters (CH3OH)n and (H2O)n. Mixed‐solvent studies indicate that the addition of a dissimilar molecule to an otherwise neat solvent cluster impedes ESPT, presumably due to a disruption of the hydrogen bonding network. Evidence is also presented for the direct measure of solvent reorganization following ESPT. For (NH3)n solvation, the solvent reorganization appears as a long‐time‐scale component (0.3 ns) on the protonated solvent formation traces.

Influence of injection conditions in reversed-phase high-performance liquid chromatography of chlorophylls and carotenoids

Abstract: The RP-HPLC analysis of chlorophylls, their degradation products (chloropigments) and carotenoids is very sensitive to the nature of the injection solvent. The effect of sample-solvent interaction can result in the production of distorted, or even false, peaks that could be erroneously interpreted as “pigment like” or as poor chromatographic resolution. The previously suggested theoretical explantion, based on differences in solvent characteristics as expressed by the Polarity Index (P′) or even by the more precise solvent strength parameter for reversed-phase systems (S) we use, was unsatisfactory. The problem seems more complex, with other parameters such as injection volume and solute concentration or solvent selectivity also playing a role. As a practical consequence, however, suggesions are made for optimum injection conditions. Also, the presence of ion-pairing reagents in the injection solvent is demonstrated to be unnecessary.

Tobacco treatment process

Abstract: Aqueous tobacco extracts are provided by subjecting finely ground tobacco laminae to extraction conditions in the presence of an aqueous solvent and an active enzyme. Then, the enzyme is deactivated, and a liquid aqueous tobacco extract is separated from the insoluble tobacco pulp which remains. The liquid extract is collected and used as a form of tobacco for smoking article manufacture.

Resolution of (±)-trans-sobrerol by lipase PS-catalyzed transesterification and effects of organic solvents on enantioselectivity

Abstract: Resolution of the mucolytic drug (±)- trans -sobrerol ( 1 ) was achieved by transesterification with vinyl acetate in organic media, catalyzed by free or immobilized Lipase PS. The enantioselectivity of the enzyme was markedly influenced by the nature of the organic solvent, but there was no correlation between enantiomeric ratio values (70–500) and either the hydrophobicity or the dielectric constant of the medium. With the enzyme immobilized onto Hyflo Super Cell and t -amyl alcohol as the solvent, the selectivity of Lipase PS for (−)- 1 was extremely high and, at 50 % conversion both (−)- trans -sobrerol and (+)- trans -sobrerol monoacetate were obtained in practically 100 % optical purity

Strategies for reducing solvent toxicity in extractive fermentations.

Abstract: The toxicity of an Alamine 336/oleyl-alcohol extraction system on Lactobacillus delbrueckii was investigated. It was shown that the solvent affected the cells through the water-soluble portion and the immiscible portion of the solvent. While immobilization significantly protected the cells from the immiscible solvent phase, the water-soluble part of the solvent still caused toxicity to the microorganisms due to diffusion of the solvent into the matrix. Adding soybean oil to the kappa-carrageenan matrix could trap the diffusing solvent molecules, and therefore reduce the toxic effect from the water soluble portion of the solvent. The protective ability of soybean oil was quantified through mathematical modeling and experimentation.