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PubMed2002

Neuropsychologic impairment and MRI abnormalities associated with chronic solvent abuse.

OBJECTIVE: Individuals chronically abusing organic solvents have been reported in the medical literature for almost four decades to have a variety of neurological abnormalities. Most have been single case reports or studies in small numbers of individuals. The purpose of this study was to evaluate the neurologic and neuropsychologic effects of chronic solvent abuse in a larger group of individuals and compare the results to a control group of other drug abusers. Attempts to estimate a dose-response relationship between solvent abuse and either neuropsychological tests or magnetic resonance imaging (MRI) abnormalities were also undertaken. METHODS: A sample of 55 solvent abusers was compared to a sample of 61 users of other drugs, especially cocaine and alcohol, on a battery of cognitive and neuropsychological tests. Fifty of the solvent abusers and 51 members of the comparison sample also underwent MRI of the brain. Comparisons were made by means of multivariate analysis of variance and covariance. RESULTS: Compared to the general population, both groups performed poorly, scoring below the mean on most neuropsychological measures. Solvent abusers performed more poorly than the comparison sample on measures of working memory and executive cognitive functions. Both groups showed evidence of abnormal MRI findings, but a greater percentage of the solvent abuse group showed such abnormalities. No clear dose-response relationship was seen between solvent abuse and abnormalities on neuropsychological tests, but a strong dose-response relationship was seen in the presence of MRI abnormalities. CONCLUSION: The findings in this study document widespread cognitive impairment, which could not be attributed to the effects of solvents entirely. These findings expand upon previous data regarding neurological abnormalities in solvent abusers, by demonstrating a dose-response relationship with MRI abnormalities. An unexpected finding was the high prevalence of neuropsychological impairment and MRI abnormalities among the comparison group. The results of this study has implications regarding low-level solvent exposure, as in the occupational setting, suggesting that MRI may be a more useful tool to sort out the presence of neurological abnormalities rather than neuropsychological tests. Since no dose-response relationship was seen between solvent abuse and neuropsychological testing, reliance upon these tests in assessing neurological injury from solvents is a highly dubious practice.

Adult↗
PubMed2003

Solubility enhancement of Cox-2 inhibitors using various solvent systems.

This study examined the solubility enhancement of 4 cox-2 inhibitors, celecoxib, rofecoxib, meloxicam, and nimesulide, using a series of pure solvents and solvent mixtures. Water, alcohols, glycols, glycerol, and polyethylene glycol 400 (PEG 400) were used as solvents and water-ethanol, glycerol-ethanol, and polyethylene glycol-ethanol were used as mixed-solvent systems. A pH-solubility profile of drugs was obtained in the pH range 7.0 to 10.9 using 0.05 M glycine-sodium hydroxide buffer solutions. Lower alcohols, higher glycols, and PEG 400 were found to be good solvents for these drugs. The aqueous solubility of celecoxib, rofecoxib, and nimesulide could be enhanced significantly by using ethanol as the second solvent. Among the mixed-solvent systems, PEG 400- ethanol system had highest solubilization potential. In the case of meloxicam and nimesulide, solubility increased significantly with increase in pH value. Physico-chemical properties of the solvent such as polarity, intermolecular interactions, and the ability of the solvent to form a hydrogen bond with the drug molecules were found to be the major factors involved in the dissolution of drugs by pure solvents. The greater the difference in the polarity of the 2 solvents in a given mixed solvent, the greater was the solubilization power. However, in a given mixed-solvent system, the solubilization power could not be related to the polarity of the drugs. Significance of the solubility data in relation to the development of formulations has also been discussed in this study.

Celecoxib↗
PubMed2001

Hearing loss among workers exposed to moderate concentrations of solvents.

OBJECTIVES: It is known that some industrial organic solvents are ototoxic. This study was aimed at evaluating the hearing effects of a mixture of organic solvents alone or in combination with noise on employees in paint and lacquer enterprises. The concentration of solvents was below the occupational exposure limits (OEL) for most of the subjects. METHODS: Altogether 517 subjects were divided into the following three groups: persons with no risk due to noise or organic solvent exposure at the workplace, workers exposed to organic solvents only, and workers exposed to both organic solvents and noise. RESULTS: The relative risk (RR) of hearing loss in the solvent-only exposure group was significantly increased (RR 4.4 and RR 2.8 for noise exposure of < 80 dB-A and < 85 dB-A, respectively) in a wide range of frequencies (2-8 kHz). No additional risk in the solvent + noise exposure group was found (RR 2.8). Hearing thresholds were significantly poorer in a wide range of frequencies (1-8 kHz) for both groups exposed to solvents, when compared with the reference group. The mean hearing thresholds at frequencies of 2-4 kHz were poorer for workers exposed to solvents + noise than for the solvent-only group; this finding suggests an additional effect for noise. However, there was no correlation between hearing loss and the extent of solvent exposure. CONCLUSIONS: The results indicate that occupational organic solvent exposure at moderate concentrations increases the risk of hearing loss, and the ototoxic effects should be considered when the health effects of exposed workers are monitored.

Adult↗
PubMed2000

[Study on the rule of solvent strength in reversed-phase liquid chromatography].

Based on the physical meanings of Z (total moles of the released solvent at the contact region between solute and stationary phase), and j(the slope of the linear plot of lg I versus Z, a constant relating to the affinity of organic solvent to the stationary phase) of stoichiometric displacement model for retention (SDM-R) of solute in liquid chromatography(LC), both Z and j could be employed to characterize solvents, therefore, Z value only can be used as a characterization parameter for fixed solute and stationary phase. However, the parameter j is independent of solutes. As long as phase is given, j can be employed as a new characterization parameter of organic solvent strength in LC. With the homologues of methanol, ethanol and n-propanol as organic solvents in mobile phase and n-alkylalcohols as solutes, both the SDM-R and Snyder's empirical equation were tested, and compared with the corresponding parameters obtained from Snyder's empirical equation. With S [the slope of the linear plot of lg k' (k' is capacity factor) vs psi(volume fraction of organic solvent in mobile phase)] and lg kw0(the intercept of this plot), it was found that the two linear plots with the SDM-R, lg k' vs the composition of mobile phase and lg I vs Z were better than the corresponding plots with Snyder's empirical equation. The results indicate that Z, lg I and j decrease with the increase in the molecular size of the organic solvent of the homologue. This fact indicates that the solvent strength in LC depends on the size of solvent molecules. And the greater the solvent molecules, the stronger the solvent strength is. Furthermore the solvent strength was found to follow homologous rule. The j value may become a new parameter for the characterization of organic solvent strength in LC.

Chemical Phenomena↗
PubMed2002

Effects of solvents on the electron configurations of the low-spin dicyano[meso-tetrakis(2,4,6-triethylphenyl)porphyrinato]iron(III) complex: importance of the C-H...N weak hydrogen bonding.

There are two types of electron configurations, (d(xy))(2)(d(xz), d(yz))(3) and (d(xz), d(yz))(4)(d(xy))(1), in low-spin iron(III) porphyrin complexes. To reveal the solvent effects on the ground-state electron configurations, we have examined the (13)C- and (1)H-NMR spectra of low-spin dicyano[meso-tetrakis(2,4,6-triethylphenyl)porphyrinato]ferrate(III) in a variety of solvents, including protic, dipolar aprotic, and nonpolar solvents. On the basis of the NMR study, we have reached the following conclusions: (i) the complex adopts the ground state with the (d(xz), d(yz))(4)(d(xy))(1) electron configuration, the (d(xz), d(yz))(4)(d(xy)())(1) ground state, in methanol, because the d(pi) orbitals are stabilized due to the O-H...N hydrogen bonding between the coordinated cyanide and methanol; (ii) the complex also exhibits the (d(xz), d(yz))(4)(d(xy))(1) ground state in nonpolar solvents, such as chloroform and dichloromethane, which is ascribed to the stabilization of the d(pi) orbitals due to the C-H...N weak hydrogen bonding between the coordinated cyanide and the solvent molecules; (iii) the complex favors the (d(xz), d(yz))(4)(d(xy))(1) ground state in dipolar aprotic solvents, such as DMF, DMSO, and acetone, though the (d(xz), d(yz))(4)(d(xy))(1) character is less than that in chloroform and dichloromethane; (iv) the complex adopts the (d(xy))(2)(d(xz), d(yz))(3) ground state in nonpolar solvents, such as toluene, benzene, and tetrachloromethane, because of the lack of hydrogen bonding in these solvents; (v) acetonitrile behaves like nonpolar solvents, such as toluene, benzene, and tetrachloromethane, though it is classified as a dipolar aprotic solvent. Although the NMR results have been interpreted in terms of the solvent effects on the ordering of the d(xy) and d(pi) orbitals, they could also be interpreted in terms of the solvent effects on the population ratios of two isomers with different electron configurations. In fact, we have observed the unprecedented EPR spectra at 4.2 K which contain both the axial- and large g(max)-type signals in some solvents such as benzene, toluene, and acetonitrile. The observation of the two types of signals has been ascribed to the slow interconversion on the EPR time scale at 4.2 K between the ruffled complex with the (d(xz), d(yz))(4)(d(xy))(1) ground state and, possibly, the planar (or nearly planar) complex with the (d(xy))(2)(d(xz), d(yz))(3) ground state.

Journal Article↗
PubMed1986

Solvation properties of ubiquinone-10 in solvents of different polarity.

The solvation properties of ubiquinone-10 and ubiquinol-10 in a wide variety of solvents of polarity varying from alkanes to water are reported. Greatest solubility is observed in solvents of intermediate polarity and particularly where low polarity is combined with a pronounced tendency to interact with the benzoquinone substituent of the ubiquinone molecule. This includes solvents like chloroform and benzene. Ubiquinone-10 is somewhat less polar than ubiquinol-10 as judged by comparative solubilities of the two molecules. Proton-NMR chemical shift measurements and aggregation studies in selected solvents indicate that in ubiquinone-10 in the liquid phase and in solution in hydrocarbons like dodecane the molecules have a preferred association possibly involving stacking of the benzoquinone rings. Surface balance studies indicated that the surface-active character of ubiquinone-10 is relatively weak and only in a comparatively polar and highly structured solvent, formamide, was there evidence of an effect on surface tension of the solvent. The critical micelle concentration in this solvent was estimated to be about 5 microM on the basis of surface tension measurements. Ubiquinone-10 is well known to form virtually insoluble monolayers at the air/water interface. Studies of the partition of ubiquinone-10 in binary mixtures of solvents suggest that the interaction of the benzoquinone ring substituent with structured polar solvents is considerably weaker than the internal cohesion between molecules of the solvent. No evidence on the basis of wide-angle X-ray diffraction measurements was obtained to indicate that solvent molecules were a component of the crystal lattice of ubiquinone-10 that had precipitated from solvent mixtures.

Alkanes↗
PubMed1986

Effects of organic solvent vehicles on benzo[a]pyrene metabolism in rabbit lung microsomes.

In order to study the metabolism of benzo[a]pyrene (BP), it must be dissolved in an organic solvent vehicle for delivery to the tissue. We studied the effects of five organic solvent vehicles, i.e. dimethyl sulfoxide (DMSO), acetone, methanol, ethanol, and ethyl acetate, on benzo[a]pyrene hydroxylase activity and the BP metabolite profile in rabbit lung microsomes. Fluorescence detection of 3- and 9-OH-BP was used to evaluate benzo[a]pyrene hydroxylase activity, and the BP metabolite profile was obtained by HPLC analysis. All solvent vehicles inhibited benzo[a]pyrene hydroxylase in a dose-dependent manner. When the smallest volume of each solvent (10 microliter/ml reaction mixture) was employed, the resulting enzyme activities as related to solvent type, from highest to lowest, were DMSO greater than or equal to methanol greater than ethanol greater than or equal to acetone greater than ethyl acetate. HPLC analysis of BP metabolites formed in the presence of the five solvent vehicles showed that production of all metabolites was greatest when DMSO was used and that linearity of product formation was retained longer with DMSO. The metabolites produced when DMSO was used as the solvent were BP-9,10-diol, BP-4,5-diol, BP-7,8-diol, BP-1,6-quinone, BP-3,6-quinone and 3-OH-BP. A similar metabolite profile was obtained when reactions were carried out with methanol as the solvent vehicle, although the magnitude of production was less than with DMSO. When acetone was used, there were greater amounts of BP-4,5-diol and BP quinone formation and lesser amounts of 3-OH-BP formed than with DMSO or methanol. When ethanol or ethyl acetate was used as a solvent, BP-9,10-diol and 3-OH-BP were the only metabolites produced. These results indicate that all solvent vehicles studied inhibit benzo[a]pyrene hydroxylase from rabbit lung microsomes in a dose-dependent manner and that the magnitudes and types of metabolites formed are highly dependent upon the specific solvent used as the vehicle. The study also indicates that DMSO is probably the solvent vehicle of choice for study of BP metabolism in rabbit lung microsomes.

Acetates↗
PubMed1993

Organic solvents increase membrane fluidity and affect bile flow and K+ transport in rat liver.

Following the earlier observation that inhalation of volatile lipid solvents and of narcotic gases causes cholestasis, we studied the effects of various organic solvents on bile flow, plasma membrane fluidity and potassium movement in rat liver. Both in vivo and in the isolated perfused liver, applications of CCl4, CHCl3, dichloromethane, trichloroethylene, halothane, benzene and cyclohexane elicited rapid and sustained but reversible cholestasis. A transient phase of choleresis was observed prior to and after cholestasis, during the increase and fall in liver tissue solvent concentrations, respectively. Tissue concentrations required to produce cholestasis were lower the higher the lipophilicity of the solvent. Membrane fluidity was measured in isolated basolateral liver cell membranes by fluorescence polarization. Fluidity increased with increasing solvent concentration, the increase being associated with either biphasic stimulation and inhibition of membrane enzymes (Na+,K(+)-ATPase, 5'nucleotidase) or with inhibition alone (Mg(2+)-ATPase). In the isolated perfused liver, application of organic solvents caused hepatic uptake of K+ that was followed by K+ release upon withdrawal of the solvent. The magnitude of K+ uptake elicited by the solvent was comparable with the effect of blocking K+ channels with 2 mM Ba2+, but Ba2+ was ineffective in the presence of the solvent. In contrast, application of ouabain caused K+ release in equal amounts in the absence and presence of the solvent, indicating that K+ uptake elicited by the solvent results from inhibition of K+ efflux through K+ channels rather than stimulation of the Na+,K+ pump. The data show that cholestasis elicited by lipid solvents is associated with an increase in membrane fluidity and with disturbance of liver K+ homeostasis. The significance of these observations is discussed with respect to other models of experimental cholestasis.

Animals↗
PubMed2004

Microparticle formation and its mechanism in single and double emulsion solvent evaporation.

The emulsification is the first step of the emulsification solvent evaporation method and has been extensively investigated. On the contrary the second step, the solvent transport out from the emulsion droplets that determine the particle morphology and with great influence on the microparticles encapsulation and release behavior has been scarcely studied. This study investigates the mechanism of the solvent elimination from the emulsion droplets and its influence on the particle morphology, encapsulation and release behavior. Usually, the solvent is highly volatile that makes the solvent elimination process very fast thus difficult to observe. In order to observe in detail the microparticle formation, the initial emulsion was monitored by optical microscope under controlled solvent evaporation conditions. The results from the optical microscopic observations corroborated with laser diffractometry analysis showed that in single emulsion formulations, spherical microparticles are formed by accelerated solvent elimination due to the combined effects of high solvent volatility and polymer precipitation. The solvent expulsion accompanied by important shrinkage generates on the microparticle surface a thin layer of nanoparticles attested by scanning electron microscopy and laser diffractometry. During the intense solvent elimination, the encapsulated substance is drained, affecting the loading efficiency. Furthermore, it will concentrate towards the microparticle surface contributing to the initial burst release. In double emulsion formulations, microparticles with different morphologies are generated due to the presence of the aqueous-phase microdroplets inside the emulsion droplet. During the solvent elimination, these microdroplets generally coalesce under the pressure of the precipitating polymer. Depending mainly on the polymer concentration and emulsification energies, the final microparticles will be a mixture of honeycomb, capsule or plain structure. During the shrinkage due to the incompressibility of the inner microdroplets, the precipitating polymer wall around them may break forming holes through which the encapsulated substance is partly expulsed. Through these holes, the encapsulated substance is further partitioning with the external aqueous phase during solvent evaporation and contributes to the initial burst release during the application.

Capsules↗
PubMed1997

Thermophilic proteins: stability and function in aqueous and organic solvents.

The molecular stability of thermophilic and hyperthermophilic enzymes generally reflects the growth temperatures of the parent organisms. Extracellular enzymes from the hyperthermophilic Archaea typically show very high levels of thermal stability and a number of enzymes with Tm values of greater than 100 degrees C have been reported. The mechanisms responsible for high molecular stability are typically intrinsic characteristics of the protein, as shown by the comparative stabilities of many native and recombinant proteins. However, some extrinsic stabilisation mechanisms have been demonstrated. High levels of thermal stability are positively correlated with stability in the presence of other denaturing agents, including detergents and organic solvents. This correlation suggests a common denaturation pathway where molecular mobility/flexibility is the prime determinant of susceptibility to irreversible denaturation. In single phase organic-aqueous solvents, protein destabilisation occurs via solvent-induced alteration to the protein hydration shell. However, correlations between protein stability and solvent hydrophobicity are unreliable. In two-phase organic-aqueous systems, interfacial denaturation predominates and is a function of both interfacial tension and interfacial surface area. Intracellular enzymes are protected from interfacial denaturation but are potentially susceptible to direct organic solvent effects, possibly depending on the role of the cell wall and cell membrane in the partitioning of the organic solvent into the cell cytoplasm. Immobilisation of thermophilic enzymes provides a method for enhancing both the thermal and solvent stabilities of thermophilic and mesophilic enzymes. Multi-point covalent immobilisation to glyoxal-agarose enhances thermal stability and limits protein-protein inactivation mechanisms. Miscible organic solvents have a profound influence on the specificities of enzyme reactions. The presence of high concentrations of miscible organic solvents may induce gross changes in substrate specificity and/or more subtle alterations in chiral selectivity. Correlations between the variation in enantioselectivity and both solvent hydrophobicity and solvent dielectric constant have been demonstrated although some recent studies implicate the formation of specific solvent-enzyme complexes which directly affect reaction kinetics.

Archaea↗
PubMed1984

Monte Carlo simulation of the influence of solvent on nucleic acid base associations.

The results of Monte Carlo calculations of the association between nucleic acid bases in a nonpolar solvent (CCl4) are described. The influence of the solvent on planar and stacked associations of bases was examined by analyzing the total energy of the system, including solute-solute, solute-solvent, and solvent-solvent contributions. Good quantitative agreement with the available experimental data was obtained. Solute-solvent interactions are primarily determined by dispersion forces; consequently, solute-solvent interactions vertical to the solute plane that maximize dispersion interactions are most favored, and a rough proportionally between solute-solvent energy and the surface of the solute was observed. Analysis of solvent-solvent energy is not necessarily reduced when surface area decreases, contrary to the simple cavity concept. "Single molecule probe" calculations were performed to explain the differences in base associations in H2O and CCl4. In CCl4 dispersion forces dominate and planar complexes are stabilized by maximum exposure of molecular planes to the solvent. In H2O electrostatic forces dominate so that the most stable structures are stacked association that allow the maximum number of hydrophilic centers to be exposed to the solvent.

Adenine↗
PubMed2001

Probing the effect of vehicles on topical delivery: understanding the basic relationship between solvent and solute penetration using silicone membranes.

PURPOSE: In the present study we examined the relationship between solvent uptake into a model membrane (silicone) with the physical properties of the solvents (e.g., solubility parameter, melting point, molecular weight) and its potential predictability. We then assessed the subsequent topical penetration and retention kinetics of hydrocortisone from various solvents to define whether modifications to either solute diffusivity or partitioning were dominant in increasing permeability through solvent-modified membranes. METHODS: Membrane sorption of solvents was determined from weight differences following immersion in individual solvents, corrected for differences in density. Permeability and retention kinetics of 3H-hydrocortisone, applied as saturated solutions in the various solvents, were determined over 48 h in horizontal Franz-type glass diffusion cells. RESULTS: Solvent sorption into the membrane could be related to differences in solubility parameters, MW and hydrogen bonding (r2=0.76). The actual and predicted volume of solvent sorbed into the membrane was also found to be linearly related to Log hydrocortisone flux, with changes in both diffusivity and partitioning of hydrocortisone observed for the different solvent vehicles. CONCLUSIONS: A simple structure-based predictive model can be applied to the sorption of solvents into silicone membranes. Changes in solute diffusivity and partitioning appeared to contribute to the increased hydrocortisone flux observed with the various solvent vehicles. The application of this predictive model to the more complex skin membrane remains to be determined.

Administration, Topical↗
PubMed2004

Photophysical properties of 2-amino-9,10-anthraquinone: evidence for structural changes in the molecule with solvent polarity.

The photophysical properties of 2-amino-9,10-anthraquinone (2AAQ) have been investigated in different solvents and solvent mixtures and correlated with the Lippert-Mataga solvent polarity parameter, Deltaf. In the low solvent polarity region with Deltaf < ca. 0.1, the dye shows unusually high fluorescence quantum yields (Phif) and lifetimes (tauf) in comparison to those in other solvents of medium to high polarities. Similarly, the radiative rate constants (kf) are relatively lower and the non-radiative rate constants (knr) are relatively higher in the low polarity solvents in comparison to those in the medium to high polarity solvents. The current results have been rationalized assuming that the dye adopts different structural forms below and above the Deltaf value of approximately 0.1. It is inferred that in the low solvent polarity region the dye exists in a non-planar structure, with its 2-NH2 plane away from that of the 9,10-anthraquinone moiety in the ground state. In solvents of medium to high polarities, the dye exists in a polar intramolecular charge transfer (ICT) structure, where the amino lone pair of the 2-NH2 group is in strong resonance with the anthraquinone pi-cloud in the ground state. In all the solvents, however the dye is inferred to exist in the ICT structure in its excited (S1) state. Supportive evidence for the above hypothesis has been obtained from the solvent polarity effect on the Stokes' shifts for the dye. Quantum chemical studies on the structures of 2AAQ dye in the gas phase also give qualitative support for the inferences drawn from the photophysical properties of the dye in different solvents.

Anthraquinones↗
PubMed2006

Impulsive solvent heating probed by picosecond x-ray diffraction.

The time-resolved diffraction signal from a laser-excited solution has three principal components: the solute-only term, the solute-solvent cross term, and the solvent-only term. The last term is very sensitive to the thermodynamic state of the bulk solvent, which may change during a chemical reaction due to energy transfer from light-absorbing solute molecules to the surrounding solvent molecules and the following relaxation to equilibrium with the environment around the scattering volume. The volume expansion coefficient alpha for a liquid is typically approximately 1 x 10(-3) K(-1), which is about 1000 times greater than for a solid. Hence solvent scattering is a very sensitive on-line thermometer. The decomposition of the scattered x-ray signal has so far been aided by molecular dynamics (MD) simulations, a method capable of simulating the solvent response as well as the solute term and solute/solvent cross terms for the data analysis. Here we present an experimental procedure, applicable to most hydrogen containing solvents, that directly measures the solvent response to a transient temperature rise. The overtone modes of OH stretching and CH3 asymmetric stretching in liquid methanol were excited by near-infrared femtosecond laser pulses at 1.5 and 1.7 microm and the ensuing hydrodynamics, induced by the transfer of heat from a subset of excited CH3OH* to the bulk and the subsequent thermal expansion, were probed by 100 ps x-ray pulses from a synchrotron. The time-resolved data allowed us to extract two key differentials: the change in the solvent diffraction from a temperature change at constant density, seen at a very short time delay approximately 100 ps, and a term from a change in density at constant temperature. The latter term becomes relevant at later times approximately 1 mus when the bulk of liquid expands to accommodate its new temperature at ambient pressure. These two terms are the principal building blocks in the hydrodynamic equation of state, and they are needed in a self-consistent reconstruction of the solvent response during a chemical reaction. We compare the experimental solvent terms with those from MD simulations. The use of experimentally determined solvent differentials greatly improved the quality of global fits when applied to the time-resolved data for C2H4I2 dissolved in methanol.

Chemistry, Physical↗
PubMed2001

Structural and thermodynamic analysis of the binding of solvent at internal sites in T4 lysozyme.

To investigate the structural and thermodynamic basis of the binding of solvent at internal sites within proteins a number of mutations were constructed in T4 lysozyme. Some of these were designed to introduce new solvent-binding sites. Others were intended to displace solvent from preexisting sites. In one case Val-149 was replaced with alanine, serine, cysteine, threonine, isoleucine, and glycine. Crystallographic analysis shows that, with the exception of isoleucine, each of these substitutions results in the binding of solvent at a polar site that is sterically blocked in the wild-type enzyme. Mutations designed to perturb or displace a solvent molecule present in the native enzyme included the replacement of Thr-152 with alanine, serine, cysteine, valine, and isoleucine. Although the solvent molecule was moved in some cases by up to 1.7 A, in no case was it completely removed from the folded protein. The results suggest that hydrogen bonds from the protein to bound solvent are energy neutral. The binding of solvent to internal sites within proteins also appears to be energy neutral except insofar as the bound solvent may prevent a loss of energy due to potential hydrogen bonding groups that would otherwise be unsatisfied. The introduction of a solvent-binding site appears to require not only a cavity to accommodate the water molecule but also the presence of polar groups to help satisfy its hydrogen-bonding potential. It may be easier to design a site to accommodate two or more water molecules rather than one as the solvent molecules can then hydrogen-bond to each other. For similar reasons it is often difficult to design a point mutation that will displace a single solvent molecule from the core of a protein.

Amino Acid Substitution↗
PubMed2000

Chlorophyll a self-assembly in polar solvent-water mixtures.

The conversion of chlorophyll a (Chl a) monomers into large aggregates in six polar solvents upon addition of water has been studied by means of absorption, fluorescence spectroscopy and fluorescence lifetime measurements for the purpose of elucidating the various environmental factors promoting Chl a self-assembly and determining the type of its organization. Two empirical solvent parameter scales were used for quantitative characterization of the different solvation properties of the solvents and their mixtures with water. The mole fractions of water f1/2 giving rise to the midpoint values of the relative fluorescence quantum yield were determined for each solvent, and then various solvent-water mixture parameters for the f1/2 values were compared. On the basis of their comparison, it is concluded that the hydrogen-bonding ability and the dipole-dipole interactions (function of the dielectric constant) of the solvent-water mixtures are those that promote Chl a self-assembly. The influence of the different nature of the non-aqueous solvents on the Chl aggregation is manifested by both the different water contents required to induce Chl monomer-->aggregate transition and the formation of two types of aggregates at the completion of the transition: species absorbing at 740-760 nm (in methanol, ethanol, acetonitrile, acetone) and at 667-670 nm (in pyridine and tetrahydrofuran). It is concluded that the type of Chl organization depends on the coordination ability and the polarizability (function of the index of refraction) of the organic solvent. The ordering of the solvents with respect to the f1/2 values--methanol < ethanol < acetonitrile < acetone < pyridine < tetrahydrofuran--yielded a typical lyotropic (Hofmeister) series. On the basis of this solvent ordering and the disparate effects of the two groups of solvents on the Chl a aggregate organization, it is pointed out that the mechanism of Chl a self-assembly in aqueous media can be considered a manifestation of the Hofmeister effect, as displayed in the lipid-phase behavior (Koynova et al., Eur. J. Biophys. 25, 261-274, 1997). It relates to the solvent ability to modify the bulk structure and to distribute unevenly between the Chl-water interface and bulk liquid.

Chlorophyll↗
PubMedDate not supplied

Photophysical properties of coumarin-30 dye in aprotic and protic solvents of varying polarities.

Experimental results on various photophysical properties of coumarin-30 (C30) dye, namely, Stokes' shift (Deltanu), fluorescence quantum yield (Phi(f)), fluorescence lifetime (tau(f)), radiative rate constant (k(f)) and nonradiative rate constant (k(nr)), as obtained using absorption and fluorescence measurements have been reported. Though in most of the solvents the properties of C30 show more or less linear correlation with the solvent polarity function, Deltaf = [(epsilon - 1)/(2epsilon + 1) - (n(2) - 1)/(2n(2) + 1)], they show unusual deviations in nonpolar solvents at one end and in high-polarity protic solvents at the other end. From the solvent polarity and temperature effect on the photophysical properties of the dye, following inferences have been drawn: (1) in nonpolar solvents, the dye exists in a nonpolar structure, where its 7-NEt(2) substituent adopts a pyramidal configuration and the amino lone pair is out of resonance with the benzopyrone pi cloud; (2) in medium to higher polarity solvents, the dye exists in a polar intramolecular charge transfer structure, where the 7-NEt(2) group and the 1,2-benzopyrone moiety are in the same plane and the amino lone pair is in resonance with the benzopyrone pi cloud; (3) in protic solvents, the dye-solvent intermolecular hydrogen bonding influences the photophysical properties of the dye; and (4) in high-polarity protic solvents, the excited C30 undergoes a new activation-controlled nonradiative deexcitation process because of the involvement of a twisted intramolecular charge transfer (TICT) state. Contrary to most other TICT molecules, the activation barrier for this deexcitation process in C30 is observed to increase with solvent polarity. A rational for this unusual behavior has been given on the basis of the solvent polarity-dependent stabilization and crossing of relevant electronic states and the relative propensity of interconversion among these states.

Coloring Agents↗
PubMed1995

Solvent selection for whole cell biotransformations in organic media.

Although they were used historically as antimicrobial agents, there is a modern requirement to devise organic solvent systems for exploitation in the biotransformation by intact cells of substrates that are poorly soluble in water. Water-immiscible solvents are normally less cytotoxic than are water-miscible ones. While a unitary mechanism is excluded, damage to the membrane remains the likeliest major mechanism of cytotoxicity, and may be conveniently assessed using an electronic biomass probe. Studies designed to account for the mechanisms of action of general anesthetics and of uncouplers parallel those designed to account for the cytotoxicity of organic solvents. Although there are hundreds of potential physical descriptors of solvent properties, many are broadly similar to each other, such that the intrinsic dimensionality of solvent space is relatively small (< 10). This opens up the possibility of providing a rational biophysical basis for the optimization of the solvents used for biotransformations. The widely used descriptor of solvent behavior, log P (the octanol:water partition coefficient), is a composite of more fundamental molecular descriptors; this explains why there are rarely good correlations between cytotoxicity and log P when a wide variety of solvents is studied. Although the intrinsic dimensionality of solvent space is relatively small, pure solvents still populate it rather sparsely. Thus, mixtures of solvents can and do provide the opportunity of obtaining a solvent optimal for a biotransformation of interest.

Alcohols↗