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Utility of 1-octanol/octane mixed solvents for the solvent extraction of aluminum(III), gallium(III), and indium(III) with 8-quinolinol.

Using 1-octanol/octane mixed solvents, the extraction of aluminum(III), gallium(III) and indium(III) with 8-quinolinol was carried out at 25 degrees C. The formation constants of the respective metal(III) 8-quinolinolates in the aqueous phase and their partition constants between the mixed solvents and water were determined based on an analysis of the extraction equilibria. The relationship between the partition constants of 8-quinolinol and its complexes was analyzed by the regular solution theory. The molar volumes of aluminum(III), gallium(III) and indium(III) 8-quinolinolates, calculated from the present results, suggest that the electrostriction effect functions in complex forming. It has been found that octane/1-octanol mixed solvents were available not only for the extraction of metal ions, but also for determining the formation constants of these metal 8-quinolinolates in the aqueous phase and their partition constants.

1-Octanol↗

Subcutaneous secretin in dogs: influence of solvent and volume of solvent.

Pancreatic secretion in response to subcutaneously injected secretin was studied in three dogs with chronic pancreatic and gastric fistulas. Three solvents: saline, gelatin, carboxymethylcellulose (CMC); two volumes of solvent: 2 and 6 ml; and two doses of secretin: 75 and 150 clinical units were tested. Gelatin was more effective than CMC in prolonging the action of secretin; the duration of the plateau of secretion was about twice as long with gelatin as with saline. Increasing the volume of solvent from 2 to 6 ml also increased the total duration of secretion and total HCO-3 output. It is concluded that gelatin is a suitable vehicle for prolonging the action of secretin.

Analysis of Variance↗

[Solvent-induced chronic encephalopathy; the 'solvent team' project].

Long-term exposure to organic solvents can result in damage of the central nervous system. The WHO recognises the following stages: organic affective syndrome, mild chronic toxic encephalopathy (CTE), and severe CTE. There is no golden standard for the diagnosis of CTE. Mild CTE is characterised by fatigue, mood disturbances, memory and attention disorders. In the Netherlands, a so-called 'solvent team' consisting of an occupational physician, a neurologist, a neuropsychologist and an occupational hygienist, assesses patients suspected of having CTE. The diagnostic procedure consists of three steps: (a) interview and blood tests, (b) the computer-based Neurobehavioral Evaluation System, and (c) assessment of an exposure index, neuropsychological investigation, and clinical neurological examination. In the period 1997-1999 approximately 250 patients were assessed yearly in the Netherlands; resulting in 50 diagnoses of mild CTE a year. The real incidence is most likely higher at present, but will decline due to diminished exposure to organic solvents.

Chronic Disease↗

Influence of organic solvents and pH on some characteristics of influenza virus A(H1N1). Note 1. Influence of organic solvents on the spectral characteristics of fluoresceine isothiocyanate-conjugated influenza virus A(H1N1).

The fluorescence of fluoresceine isothiocyanate (FITC)-conjugated influenza virus A(H1N1) was enhanced following addition of ethanol, acetone or dimethylsulfoxide (DMSO) and decreased after addition of dioxane; light scattering values increased in the presence of any of these organic solvents. The effect of the organic solvents could be correlated with the excess values delta epsilon of the dielectric constant. Out of the four organic solvents it was DMSO that caused the slightest changes in the fluorescence and light scattering of the FITC/virus system.

Dose-Response Relationship, Drug↗

Studies related to nitrosamide formation: nitrosation in solvent: water and solvent systems, nitrosomethylurea formation in the rat stomach and analysis of a fish product for ureas.

Nitrous acid (HNO2) was partly extracted from water by organic solvents, especially polar ones. Carbaryl was nitrosated in solvent: water mixtures most rapidly when nonpolar solvents, e.g. methylene chloride, carbon tetrachloride and hexane, were used. Under given conditions, carbaryl was nitrosated in methylene chloride:water mixtures 20 times faster than in water alone, mainly because of its insolubility in water. For ethylurea, hexylurea, ethyl N-ethyl-carbamate and aminopyrine, nitrosation by sodium sulfate-dried methylene chloride extracts of nitrous acid ('dried HNO2') was at least 88% complete after reaction for 5 seconds at 6 degrees C. Nitrosation of N-butylacetamide by the same extract proceeded more slowly, with a second-order rate constant 31,000 times greater than for nitrosation in water at pH 2. Butylacetamide was nitrosated in methylene chloride by equivalent concentrations of 'dried HNO2', dinitrogen trioxide and dinitrogen tetroxide at similar rates. Nitrosomethylurea (NMU) formation was measured radioactively in the stomach contents of rats fed [3H]methylurea (MU) and sodium nitrite. When both compounds were given in the food (100 mg MU and 4 g NaNO2/kg) and the rats were killed 3 hours later, the NMU yield was 0.46% of the MU. When the food also contained 11.5 g sodium ascorbate/kg, NMU production was completely inhibited. With 2-4 g/1 sodium nitrite in the drinking water and MU in the food, no NMU was detected. Ureas were determined in dried, salted bonito fish from Japan, by a method involving ion-exchange and paper chromatography. The fish sample contained 80 mg urea/kg, but no MU. When the fish was nitrosated at pH 1 and then denitrosated at pH 0, 25 mg MU/kg was detected. Mu identity was confirmed by mass spectrometry.

Animals↗

The synthetic rate of dipeptide catalyzed by organic solvent-stable protease from Pseudomonas aeruginosa PST-01 in the presence of water-soluble organic solvents.

The initial synthetic rates of peptide Cbz-Arg-Leu-NH(2) from Cbz-Arg and Leu-NH(2) using PST-01 protease in the presence and absence of organic solvents were investigated under various conditions. The synthetic rates of Cbz-Arg-Leu-NH(2) in the presence of 50% (v/v) methanol, 50% (v/v) N,N-dimethylformamide (DMF) and 60% (v/v) dimethyl sulfoxide (DMSO) were 1.6-, 2.4-, and 5.1-times higher than that in the absence of organic solvent, respectively. The PST-01 protease was not only stable in the presence of organic solvents but also exhibited high reaction rates in the presence of methanol, DMF, and DMSO. When the Cbz-Arg concentration was lower than 60mM or the Leu-NH(2) concentration was lower than 400mM, the initial rates increased lineally with increase in their concentrations. However, the rates did not increase when the Leu-NH(2) concentration was more than 500mM. The optimum temperature and pH of the reaction were 40 degrees C and 7.0, respectively.

Journal Article↗

Solvent effects on chemical processes. 10. Solubility of alpha-cyclodextrin in binary aqueous-organic solvents: relationship to solid phase composition.

The equilibrium solubility at 25 degrees C of alpha-cyclodextrin was measured in several binary aqueous-organic solvent mixtures, the organic cosolvents being methanol, 2-propanol, ethylene glycol, and acetone. Solubility maxima were observed as the solvent composition was varied from pure water to pure cosolvent. The maximum in methanol systems was hardly detectable, but it was very pronounced in 2-propanol and acetone, and two maxima were seen in the ethylene glycol system. Karl Fischer analysis of the solid phase isolated from 2-propanol/water equilibrium systems showed that alpha-cyclodextrin hexahydrate is the stable form in water, whereas a solid phase containing three water molecules per molecule of alpha-cyclodextrin is the stable form in the presence of 2-propanol. The appearance of a solubility maximum in this system, and by extension presumably in the other cosolvent systems, is attributed to the existence of more than one stable solid phase of alpha-cyclodextrin.

Crystallization↗

[Polyneuropathy and encephalopathy caused by organic solvents and mixed solvent solutions. Occupational medicine and neurologic aspects of a new occupational disease].

Solvent induced polyneuropathy and encephalopathy have been acknowledged quite recently as occupational diseases in Germany. For compensation first of all the diagnosis has to be proven. For differential diagnosis other known causes as well as non-organic mental diseases must be taken into consideration. The causality between proven exposures and diagnosed disease has at least to be probable. To evaluate causation extensive experience of the experts is needed. In this context scientific criteria regarding neurotoxicity of the solvent, duration of exposure, individual aspects of non-occupational influences, time course of the disease are important within a through synoptic evaluation. Possibilities and limitations of sensitive diagnostic measures such as neurographic, neuropsychologic and neuroimaging examinations are discussed. The prognosis of toxic polyneuropathy and encephalopathy is in general favorable if exposure has stopped. Additionally, adequate therapy and rehabilitation measures are supportive for a good prognosis.

Brain Damage, Chronic↗

A newly isolated organic solvent tolerant Staphylococcus saprophyticus M36 produced organic solvent-stable lipase.

Thirty-eight high lipase activity strains were isolated from soil, seawater, and Brassica napus. Among them, a novel organic solvent tolerant bacterium (strain M36) was isolated from the seawater in Jiangsu, China. Isolate M36 was able to grow at high concentration of benzene or toluene up to 40% (vol/vol), and later identified as Staphylococcus saprophyticus by biochemical test and 16s ribosomal DNA sequence. No work on Staphylococcus producing lipase with organic solvent tolerance has been reported so far. The lipase of strain M36 whose activity in liquid medium was 42 U mL(-1) at 24-h incubation time was stable in the presence of 25% (vol/vol) p-xylene, benzene, toluene, and hexane.

Benzene↗

Spectroscopic studies on the cation-anion, cation-solvent and anion-solvent interactions in the LiCF3SO3/acetamide complex system.

A molten salt electrolyte composed of lithium triflate (LiCF3SO3) and acetamide (CH3CONH2) has been prepared and characterized by Raman, IR spectroscopy and ac impedance. It is found that acetamide molecule not only complexes with the Li+ cation but also interacts with the CF3SO3- anion via hydrogen bonding due to its two polar groups (C=O group and NH2 group) capable of coordinating with cations and anions, respectively. Cation-anion interaction is strengthened while cation-solvent and anion-solvent interactions are weakened with the increases of salt concentration and temperature in the LiCF3SO3/acetamide complex. The ionic conductivities of the LiCF3SO3/acetamide complex with different molar ratios depend strongly on the ionic association in the complex system.

Acetamides↗

Evaluation and selection of optimal solvents and solvent combinations in thin-layer chromatography. Application of the method to basic drugs.

A series of simple mathematical techniques for the evaluation of solvents and solvent combinations in thin-layer chromatography have been investigated. A strategy for the rapid selection of the optimum combination is proposed. It uses classification procedures based on calculation of the similarity between systems. The classification is carried out using a simple graph-theoretical procedure (Kruskal's algorithm) or numerical taxonomy. The selection of optimal sets from the clusters which appear in the classification is based on the information content as derived from Shannon's equation. The method has been applied to an RF data set for basic drugs. It is concluded that these methods indeed allow the selection of optimal systems or combination of systems.

Chromatography, Thin Layer↗

Removal of detergent and solvent from solvent-detergent-treated immunoglobulins.

The solvent-detergent (S/D) method was applied for inactivation of lipid-enveloped viruses during the production of immunoglobulins. Amberlite XAD-7 resin was used for removal of solvent (tri-n-butyl phosphate, TnBP) and detergent (Triton X-100) after the performed S/D inactivation procedure. The S/D reagents from the immunoglobulin preparation were adsorbed on Amberlite XAD-7, while immunoglobulins passed through the column and retained their biological activity. Using the method developed here, the final immunoglobulin preparation contains less than 1 ppm of Triton X-100 and less than 2 ppm TnBP.

Acrylic Resins↗

Development of the charge-transfer-to-solvent process with increasing solvent fluid density: the effect of ion pairing.

The study of the UV spectroscopic behaviour of alkali metal iodides dissolved in supercritical ammonia showed that two absorbing species contributed to the UV absorption of the solutions. The two species differed in the type of interaction of iodide with the cation, i.e. going from contact ion pairs to free iodide ion, the observed absorption band varied according to the species that prevailed as the solvent density (rho(1)) changed. This experimental evidence was supplemented with molecular dynamics simulations and electronic structure calculations which showed that at very low rho(1) when the contact ion pair is the dominant species, a sudden change from the internal charge transfer photoexcitation route to a charge-transfer-to-solvent transition occurred. This finding emphasized the importance of solvation at very low rho(1) not only for the photoexcitation process, it also allows connecting the thermodynamic behaviour of the solutes in solution with that observed in their vapour phase. We have tried to draw a consistent picture of the available information of UV photoexcitation for iodides in vapour, in solution either forming contact ion pairs or present as free iodide ions, including their behaviour in small clusters of highly polar molecules. The importance of the cation has been clearly shown in this investigation. A relation between the photoexcited electron in contact ion pairs and the solvated electron of alkali metals in small NH(3) clusters has been conjectured.

Ammonia↗

Protein-solvent preferential interactions, protein hydration, and the modulation of biochemical reactions by solvent components.

Solvent additives (cosolvents, osmolytes) modulate biochemical reactions if, during the course of the reaction, there is a change in preferential interactions of solvent components with the reacting system. Preferential interactions can be expressed in terms of preferential binding of the cosolvent or its preferential exclusion (preferential hydration). The driving force is the perturbation by the protein of the chemical potential of the cosolvent. It is shown that the measured change of the amount of water in contact with protein during the course of the reaction modulated by an osmolyte is a change in preferential hydration that is strictly a measure of the cosolvent chemical potential perturbation by the protein in the ternary water-protein-cosolvent system. It is not equal to the change in water of hydration, because water of hydration is a reflection strictly of protein-water forces in a binary system. There is no direct relation between water of preferential hydration and water of hydration.

Binding Sites↗

Particle design of tolbutamide by the spherical crystallization technique. III. Micromeritic properties and dissolution rate of tolbutamide spherical agglomerates prepared by the quasi-emulsion solvent diffusion method and the solvent change method.

With the objective of modifying the micromeritic properties of tolbutamide (i.e., to manufacture a highly functional powder form), particle design was attempted using a quasi-emulsion solvent diffusion (QESD) method, and the micromeritic properties and dissolution rate of the obtained spherical agglomerates were evaluated by comparison with agglomerates prepared by the solvent change (SC) method. For the production of tolbutamide agglomerates by the QESD method, a necessary condition was the addition of a sucrose fatty acid ester to the system as an emulsifying agent. The particle diameter of the agglomerates obtained by the QESD method depended on the size of the initially formed quasi-emulsion droplets, which in turn depended on the viscosity of the solution. In addition, the agglomerates were nearly perfectly spherical in shape. In the QESD method, the quasi-emulsion droplets crystallized instantaneously from the droplet surface inward. The resultant agglomerates were dense, had great mechanical strength and showed excellent flowability due to their perfect spherical shape. On the other hand, the agglomerates produced by the SC method were conglomerates of primary crystals, and fine, needle-like crystals formed on their surface. As a result, these agglomerates had a large specific surface area, and they therefore showed greater solubility than the agglomerates prepared by the QESD method.

Chemistry, Pharmaceutical↗

International Conference on Harmonisation; final recommendations on the revision of the permitted daily exposures for two solvents, n-methylpyrrolidone and tetrahydrofuran, according to the maintenance procedures for the guidance Q3C Impurities: Residual Solvents; Availability. Notice.

The Food and Drug Administration (FDA) is announcing final recommendations to revise the permitted daily exposures (PDEs) for two solvents, n-methylpyrrolidone (NMP) and tetrahydrofuran (THF), according to the maintenance procedures for the guidance for industry entitled "Q3C Impurities: Residual Solvents." The final recommendations were reached under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

Chemistry, Pharmaceutical↗

The role of solvent polarity in the free energy of transfer of amino acid side chains from water to organic solvents.

The transfer free energies of amino acid side chains from water to N-methylacetamide have been determined and compared with those obtained from other model systems. Although the process of transfer from water to N-methylacetamide represents transfer from a lower dielectric phase to a higher dielectric phase, the transfer free energies of most of the amino acid side chains are nearly the same as those obtained from the water to ethanol system. Among the apolar side chains studied, only the transfer free energies of methionine and the aromatic side chains are apparently influenced to some extent by the polarity of the organic solvent phase. The transfer free energies of the neutral polar side chains also exhibit significant dependence on solvent polarity. The van't Hoff plots for most of the apolar side chains exhibit nonlinear curves, indicating that the enthalpy of transfer from water to N-methylacetamide is temperature-dependent. It is suggested that to assess the contribution of the hydrophobic free energy to the stability of globular proteins, it is probably not necessary to account for variation in the internal environment of the protein.

Acetamides↗

Solubility of nonelectrolytes in polar solvents III: Alkyl p-aminobenzoates in polar and mixed solvents.

The relative solubilities of n-alkyl p-aminobenzoates in water, proplyene blycol-water mixtures, proplyene glycol, and several other pharmaceutically important solvents can be predicted on the basis of a theoretical equation. This equation relates the activity coefficient of the hydrophobic portion of the molecule to the product of its surface area and its interfacial tension [free energy per unit area of a hydrocarbon (tetradecane) against the polar or semipolar solvent of interest]. The assumptions, conclusions, and applicability of the theorectical relationship are compared to those of the Scatchard-Hildebrand approach.

Alcohols↗