Understanding Of Solvent Effects Research Articles

Dual Effect of Secondary Solutes on Binding Equilibria: Contributions from Solute-Reactant Interactions and Solute-Water Interactions.

This study examines the role of water in binding equilibria with a special focus on secondary solutes (cosolutes) that influence the equilibrium but are not constituents of the final product. Using a thermodynamic framework that includes an explicit term for the release of water molecules upon binding, this investigation reveals how solutes may alter equilibria by changing the activity of the reactants, reflected in ΔG°(obs), and by changing the chemical potential of the solvent, reflected in ΔGS. The framework is applied to four experimental binding systems that differ in the degree of electrostatic contributions. The model systems include the chelation of Ca2+ by EDTA and three host-guest reactions; the pairings of p-sulfonatocalix[4]arene with tetramethylammonium ion, cucurbit[7]uril with N-acetyl-phenylalanine-amide, and β-cyclodextrin with adamantane carboxylate are tested. Each reaction pair is examined by isothermal titration calorimetry at 25 °C in the presence of a common osmolyte, sucrose, and a common chaotrope, urea. Molar solutions of trehalose and phosphate were also tested with selected models. In general, cosolutes that enhance binding tend to reduce the solvation free energy penalty and cosolutes that weaken binding tend to increase the solvation free energy penalty. Notably, the nonpolar-nonpolar interaction between adamantane carboxylate and β-cyclodextrin is characterized by a ΔGS value near zero. The results with β-cyclodextrin, in particular, prompt further discussions of the hydrophobic effect and the biocompatible properties of trehalose. Other investigators are encouraged to test and refine the approach taken here to further our understanding of solvent effects on molecular recognition.

Understanding solvent effects on solvatomorphisms of donepezil-maleic acid

The aim of this work is to investigate the action of solvents in the preparation of donepezil-maleic acid. Five forms of donepezil-maleic acid, including: anhydrous donepezil-maleic acid (DM), donepezil-maleic acid-acetone (DM-A), donepezil-maleic acid-ethyl acetate (DM-EA), donepezil−maleic acid-ethanol (DM-E) and donepezil-maleic acid-water (DM-W), were prepared by mechanochemistry. The crystal structures of the four solvates were determined by single crystal X-ray diffraction, and structure analysis showed that solvents without OH hydrogen bond donors (acetone and ethyl acetate) were weakly connected with donepezil-maleic acid only by atypical hydrogen bonds in the lattice, while solvents containing hydrogen bond donors (ethanol and water) provided strong intermolecular interactions to maintain the spatial structure. Furthermore, the desolvation process and stability of five forms were investigated by various analytical techniques including powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. In addition, the crystal transformation relationship of the mentioned forms was explored. The result showed that DM-W was the most stable form among the five forms, which was attributed to the strong hydrogen bonding network.

Toward a Combined Molecular Dynamics and Quantum Mechanical Approach to Understanding Solvent Effects on Chemical Processes in the Pharmaceutical Industry: The Case of a Lewis Acid-Mediated SNAr Reaction

Toward a Combined Molecular Dynamics and Quantum Mechanical Approach to Understanding Solvent Effects on Chemical Processes in the Pharmaceutical Industry: The Case of a Lewis Acid-Mediated S_NAr Reaction

Solvent Effects on Skin Penetration and Spatial Distribution of the Hydrophilic Nitroxide Spin Probe PCA Investigated by EPR

Oxidative stress occurs in extrinsic skin aging processes and diseases when the enhanced production of free radicals exceeds the homeostatic antioxidant capacity of the skin. The spin probe, 3-(carboxy)-2,2,5,5-tetramethylpyrrolidin-1-oxyl (PCA), is frequently used to study the cutaneous radical production by electron paramagnetic resonance (EPR) spectroscopy. This approach requires delivering PCA into the skin, yet solvent effects on the skin penetration and spatial distribution of PCA have not been thoroughly investigated. Three solvents of ethanol, phosphate-buffered saline (PBS) and ethanol-PBS (1:1) were studied. For both human and porcine skin ex vivo, the amount of PCA in the stratum corneum (SC) was the lowest when using ethanol and very similar for PBS and ethanol-PBS. The highest amount of PCA in the viable skin layers was detected for ethanol-PBS, yet it only took up less than 5% of the total amount. The majority of PCA was localized in the SC, among which PCA with high mobility was predominantly distributed in the hydrophilic microenvironment of corneocytes and PCA with lower mobility was mainly in the less hydrophilic microenvironment of intercellular skin lipids. A higher ethanol concentration in the solvent could improve the distribution of PCA in the hydrophilic microenvironments of the SC. The results suggest that ethanol-PBS (1:1) is best-suited for delivering most PCA deep into the skin. This work enhances the understanding of solvent effects on the skin penetration and distribution of PCA and supports the utilization of PCA in studying cutaneous radical production.

Understanding solvent effects on adsorption and protonation in porous catalysts

Solvent selection is a pressing challenge in developing efficient and selective liquid phase catalytic processes, as predictive understanding of the solvent effect remains lacking. In this work, an attenuated total reflection infrared spectroscopy technique is developed to quantitatively measure adsorption isotherms on porous materials in solvent and decouple the thermodynamic contributions of van der Waals interactions within zeolite pore walls from those of pore-phase proton transfer. While both the pore diameter and the solvent identity dramatically impact the confinement (adsorption) step, the solvent identity plays a dominant role in proton-transfer. Combined computational and experimental investigations show increasingly favorable pore-phase proton transfer to pyridine in the order: water < acetonitrile < 1,4 – dioxane. Equilibrium methods unaffected by mass transfer limitations are outlined for quantitatively estimating fundamental thermodynamic values using statistical thermodynamics.

Adhesion Energies of Solvent Films to Pt(111) and Ni(111) Surfaces by Adsorption Calorimetry

Solvent/metal adhesion energies are crucial for understanding solvent effects on adsorption energies, which are, in turn, central to understanding liquid-phase catalysis, electrocatalysis, and many...

Binary mixtures of dimethyl sulfoxide with methanol, ethylene glycol, and glycerol as solvent: Solvatochromism and chemical kinetics study

The understanding of solvent effects on chemical reaction requires precise knowledge of solute-solvent interactions. Since solute-solvent interactions are much more complex in mixed solvents, the study of chemical kinetics can be valuable because of the possibility of preferential solvation. In this work, binary mixture of methanol-DMSO, ethylene glycol-DMSO, and glycerol-DMSO were selected as solvent systems to determine solvatochromic polarity parameters and investigate the solute-solvent and solvent-solvent interactions. Results showed that the variation of parameters respect to solvent composition in these mixtures were compatible with those of in deep eutectic solvents-DMSO mixtures including ethylene glycol and glycerol. Aromatic nucleophilic substitution reaction of 1-fluoro-2,4-dinitrobenzene with piperidine was also investigated in the mentioned mixtures. Kinetic data showed that the reaction strongly follows the based-catalyzed mechanism in DMSO rich region. The partial catalytic and non-catalytic rate coefficients demonstrated reasonable correlations with solvatochromic parameters.

Hyperfine Coupling Constants of the Cyclohexadienyl Radical in Benzene and Dilute Aqueous Solution

The muon hyperfine coupling constant (Aμ) of the muoniated cyclohexadienyl radical (C6H6Mu) has been directly measured in a 5 mM solution of benzene in water by the radio-frequency muon spin resonance (RF-μSR) technique. The relative shift of Aμ in aqueous solution compared with the value in neat benzene (ΔAμ/Aμ = +0.98(5)% at 293 K) can now be compared directly with theoretical predictions. Application of the RF-μSR method to other dilute systems will provide extremely important information on understanding solvent effects.

Quantifying the Molecular Origins of Opposite Solvent Effects on Protein-Protein Interactions

Although the nature of solvent-protein interactions is generally weak and non-specific, addition of cosolvents such as denaturants and osmolytes strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation that addition of glycerol oppositely affects the association constants of two antibodies, D1.3 and D44.1, with lysozyme. To resolve this conundrum, we develop a methodology based on the thermodynamic principles of preferential interaction theory and the quantitative characterization of local protein solvation from molecular dynamics simulations. We find that changes of preferential solvent interactions at the protein-protein interface quantitatively account for the opposite effects of glycerol on the antibody-antigen association constants. Detailed characterization of local protein solvation in the free and associated protein states reveals how opposite solvent effects on protein-protein interactions depend on the extent of dewetting of the protein-protein contact region and on structural changes that alter cooperative solvent-protein interactions at the periphery of the protein-protein interface. These results demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions, and establish a general methodology for predicting and understanding solvent effects on protein-protein interactions in diverse biological environments.

Understanding solvent effects in the selective conversion of fructose to 5-hydroxymethyl-furfural: a molecular dynamics investigation

Selective conversion of fructose to 5-hydroxymethyl-furfural (HMF) involves the participation of high-boiling solvents like dimethyl sulfoxide (DMSO). In order to replace DMSO with low-boiling solvents, it is imperative that we understand the effect of DMSO solvation in protecting (i) HMF from rehydration and humins formation reactions and (ii) fructose from side reactions, other than its dehydration to HMF. In the present work, molecular dynamics simulations of HMF and fructose in water and in water-DMSO mixtures are carried out using the OPLS-AA force field. Radial pair distribution functions, coordination numbers and the hydrogen-bond network between the HMF/fructose molecule and the solvent molecules are analysed. The local 3-dimensional picture of the arrangement of solvent molecules around the solute, which cannot be accessed from pair distribution functions, is also computed. We show preferential coordination of DMSO around HMF and explain how this could provide a shielding effect to the HMF molecule, thus protecting it from further rehydration to levulinic acid and formic acid and from humins formation. In the case of fructose, the presence of DMSO also reduces the number of water molecules in the immediate vicinity of fructose. Though fewer water molecules coordinate around fructose, they are bound strongly to it. Analysis of the local 3-dimensional arrangement of DMSO molecules suggests that it protects the fructose molecule from side reactions that would lead to condensation or reversion products. However, the presence of DMSO molecules does not hamper the water molecules coming into contact with the oxygen atom of the hydroxyl groups of fructose, which is required for a proton transfer from water to fructose, to initiate the dehydration reaction to HMF.

Solvent effects on Cu 2O(1 1 1) surface properties and CO adsorption on Cu 2O(1 1 1) surface: A DFT study

Based on density functional theory, together with COSMO (conductor-like solvent model) in Dmol 3, the solvent effects on both the Cu 2O(1 1 1) surface properties and the adsorption of CO on Cu 2O(1 1 1) surface have been systematically investigated. Different dielectric constants, including vacuum, liquid paraffin, methylene chloride, methanol and water, are considered. The solvent effect on Cu 2O(1 1 1) surface properties shows that the solvent favors Cu 2O(1 1 1) surface area growth. The adsorption of CO on Cu 2O(1 1 1) surface indicates that the structural parameters and adsorption energies of CO are very sensitive to the COSMO solvent model. Solvent effects can effectively improve the stability of CO adsorption on Cu 2O(1 1 1) surface and the case of C–O bond activation. The interaction of solvent molecules with Cu 2O(1 1 1) surface is compared with that of CO with Cu 2O(1 1 1). Results suggest that the solvent effect is the dominating cause for the interaction of CO with Cu 2O(1 1 1) surface in solvent, in which Cu 2O(1 1 1) shows higher catalytic activity for CO activation. But the solvent may be not the only reason promoting CO activation. These analyses give us some new insights into the understanding of solvent effects.

Understanding solvent effects on structure and reactivity of organic intermediates: a Raman study

The effect of solvent on chemical reactivity has generally been explained on the basis of the dielectric constant and viscosity. However a number of spectroscopic studies, including UV-VIS, IR and Raman, has led to numerous empirical parameters to define solvent effect based on either solvating ability or polarity scale. These parameters include solvent polarizability, dipolarity, Lewis acidity and Lewis basicity, ET(30), π*, α, β etc. However, from a structural point of view, we can separate solvation as static and dynamic processes. The static solvation basically relates to stabilization of the molecular structure by the solvent to attain the equilibrium structure, both in the intermediate and ground state. Dynamic solvation relates to solvent reorganization-induced dynamics prior to the structural reorganization to reach the equilibrium state. In this paper, we present (a) structural distortions induced by the solvent due to preferential solvation of the triplet excited state, and (b) the importance of dynamic solvation induced by vibronic coupling (pseudo-Jahn–Teller coupling). The examples include the effect of solvent on structure and reactivity of excited states of 2,2,2-trifluoroacetophenone (TFA). Based on the comparison of time resolved resonance Raman (TR3) data of TFA and other substituted acetophenone systems, it was found that change in solvent polarity indeed results in electronic state switching and structural changes in the excited state, which explains the trend in reactivity. Further, a TR3 study of fluoranil (FA) in the triplet excited state in solvents of varying polarities indicates that the structure of FA in the triplet excited state is determined by vibronic coupling effects and thus distorted structure. These experimental results have been well supported by density functional theoretical computational studies.

Understanding Solvent Effects on Luminescent Properties of a Triple Fluorescent ESIPT Compound and Application for White Light Emission

A triple fluorescent compound, N-salicylidene-3-hydroxy-4-(benzo[d]thiazol-2-yl)phenylamine (SalHBP), was dispersed in solid polymers and was developed as a white-light-emitting source in LED by using it as the first simple single compound with different configurations. The CIE coordinates were at (0.29, 0.35), close to those of pure white light. To explore speciation mechanisms in this single compound white light, SalHBP was dissolved in protic, nonpolar, and moderate polar solvent, respectively. Upon excitation, blue, green, and yellowish green emissions were observed from the three solutions at various temperatures. The conformation of SalHBP at room temperature was described by a Car-Parrinello molecular dynamics simulation. With the aid of hybrid density functional theory at the B3LYP/TZVP and PBE0/TZVP levels, three observed emission bands of SalHBP were assigned from the five most probable excited state conformations that were derived from four ground state conformations. The effect of solvent on the emission of SalHBP was summarized as a possibility for forming intermolecular hydrogen bonds between solvent and SalHBP molecules and competition between intra- and intermolecular hydrogen bonds.

Understanding solvent effects on hyperfine coupling constants of cyclohexadienyl radicals

Quantum chemical calculations have been carried out to understand better solvent effects on the isotropic muon and proton hyperfine coupling constants in the C6H6Mu• radical. Both polarizable continuum solvent models and explicit inclusion of water molecules into supermolecular complexes were used. Changes in the hyperfine couplings of in-plane hydrogen atoms are very small and difficult to discuss, partly due to relatively large experimental error bars. In contrast, the out-of-plane proton and muon hyperfine couplings exhibit more pronounced changes. These are partly due to structural changes of the radical and partly due to direct electronic polarization effects. Polarizable continuum solvent models agree well with experimental changes for benzene but overshoot the enhancement of the hyperfine couplings for water. Explicit inclusion of water molecules reduces this overestimated spin density increase and thereby tends to bring theory and experiment into closer agreement. The enhancement of the spin density on the out-of-plane hydrogen or muon atoms by the solvent environment is mainly due to an increased polarization of the singly occupied MO towards this side.

PROTEINS IN VACUO . A MORE EFFICIENT MEANS OF CALCULATING ORIENTATIONALLY-AVERAGED COLLISION CROSS SECTIONS OF PROTEIN IONS

With the aim of understanding solvent effects in protein folding, unfolding, stability and dynamic behavior, studies of protein ions in vacuo have become popular in recent years. One experimental descriptor which gives a general overview of ionic structure is the orientationally-averaged collision cross section , which is obtained from ion drift mobility (IDM) and other kinds of measurements. In modelling protein structures in vacuo with molecular dynamics simulations, it is necessary to calculate for a plurality of model structures for comparison with experiments. The collision cross section is sensitive to the roughness (concavity) of the protein surface because of the possibility of multiple collisions during an encounter between a given bath gas particle and the protein. Calculations of , though in principle straightforward, are time consuming. In the work presented below, it was investigated whether a more efficient calculation scheme can be employed without sacrificing too much accuracy. In the new scheme, atomic-scale protein surface granularity is smoothed out by a collected-atoms approach, while large-scale concavity of the protein is essentially preserved. (Received August 31, 2001; revised December 26, 2001) Bull.Chem.Soc.Ethiop. 2001, 15(2), 157-166

Ab initio conformational study of the phenylisoserine side chain of paclitaxel.

Paclitaxel (Taxol) and related compounds are important antitumor drugs, currently used for the treatment of several types of cancer. The flexible amino acidic C13 side chain is a key element of the taxoid pharmacophore, and the identification of the bioactive conformation is a top priority for a better understanding of the mode of action of these anticancer agents. The conformational features of the side chain have been investigated by Hartree-Fock ab initio and semiempirical PM3 calculations. To gain a better understanding of solvent effects, different molecular models of paclitaxel were used in the calculations. The gas-phase calculations confirm that only one conformation, named ch1 (very similar to the one found in the crystal structure of docetaxel), is present in apolar environments. The preference for this conformer has been rationalized in terms of its L shape, which minimizes steric and Coulombic interactions, and of a favorable arrangement of the glycolate moiety. When a polar solvent was simulated by different methods, a greater conformational variability was found, with different conformations differing by less than 1.5 kcal/mol. Among these conformations, only one (ch5', similar to molecule B of the crystal structure of paclitaxel) is particularly apt to interact with solvent molecules. In light of these data, it seems reasonable to assume that, when the drug is bound to the lipophilic pocket of the tubuline receptor, the C13 amino acidic side chain assumes a conformation close to ch1.

Influence of carboxylic acid association upon the lactim–lactam tautomeric equilibrium of 2-hydroxypyridines

I.r. and u.v. absorption spectroscopy in CCl4 at room temperature provides evidence for lactim–acid and lactam–acid heterodimer formation in 6-chloro-2-hydroxypyridine–acetic acid mixtures. Measurements of association constants for two types of 1:1 hydrogen-bonded complexes reveal preferential association with the lactam tautomer, leading to a shift in the apparent tautomeric equilibrium constant. These results suggest that specific interactions are of great importance in understanding solvent effects on protomeric equilibria.

Specific Solvation of Ion-Pairs: Examination of Anion-Solvent Complexes by Spectral Methods

Abstract The results of experiments performed using infrared (IR) and nuclear magnetic resonance spectroscopy support the theory that chloroform associates by hydrogen bonding to the halide ion of ion-pairs. IR spectra of dextromethorphan hydrobromide in chloroform showed the same effect. This provides a definitive, albeit qualitative, demonstration of the controversial concept of specific solvation of ion-pairs, central to an understanding of solvent effects in analysis of drugs by ion-pair partition. Quantitative implications are less clear. Indications that several molecules of chloroform may be involved in complexation are presented and discussed. Results of similar experiments with methylene chloride are inconclusive.