The solvophobic theory for the prediction of molecular conformations and biopolymer bindings in solutions with recent direct experimental tests

Molecules exposing considerable microsurface areas to the surrounding solvent such as amino acids, nucleotide bases in biopolymers, or various drug molecules, antigens, and substrates, tend to be pulled apart or pushed together as the case may be by the surrounding solvent medium. These solvophobic forces and their quantitative theory were introduced sometime earlier [O. Sinano?lu, in Molecular Associations in Biology, B. Pullman, Ed. (Academic, New York, 1968), pp. 427–445; and references therein]. The forces involve both enthalpy and entropy effects. The case in water had been shown to involve particularly strong forces but not differing in kind from other solvents. There are still somewhat contradictory views on the aqueous case, referred to in the literature as “hydrophobic bonding” treated as a phenomena unique to water and previously thought to involve only entropic effects. The temperature dependence and volumetric effects on the earlier type of “hydrophobic bonding” are presently not always reconcilable with recent experimental evidence. By contrast, the solvophobic force theory allows the calculation of the full solvent effect on various association or isomerization equilibria using its quite rigorous relations and basic data derived with it from liquids and solutions. [cf., e.g., for an early application to cis-trans azobenzene isomerization, T. Hal?ǐo?lu and O. Sinano?lu, Ann. N.Y. Acad. Sci., 158 , 308 (1969)]. The solvophobic force theory had also introduced as a measurable new quantity, “the thermodynamic microsurface area change of a reaction,” which is now finding considerable use in protein chemistry [cf., e.g., F.M. Richards and T. Richmond, in CIBA Symposium Proceedings on Molecular Interaction and Activity in Proteins (CIBA, New York, 1977)]. Solvophobic force theory has been tested and applied recently in detail in high pressure liquid chromatography (HPLC) by C. Horvàth, W. Melander, and I. Molnar [J. Chromatograph. 125 , 123 (1976)] who verified the predicted temperature, molecular surface area, and salt concentration dependence. It worked well when applied in detail to the complicated methanol–water mixtures as well. The theory also gave the first a priori derivation of the experimentally well-known protein salting-in–salting-out curve [W. Melander and C. Horvath, Arch. Biochem. Biophys. 183 , 200 (1977)]. We have now extended the theory further with new basic derivations which eliminate the need for the direct calculation of some cumbersome effects. The theory has also been recently applied to a number of new areas including drug-receptor interactions, aqueous amino acid interactions, and to multicomponent phase equilibria; the latter also of chemical engineering interest. Solvophobic interactions, although part statistical thermodynamical in nature, were shown to be usable as if they were an ordinary U(R) potential added on to quantum-chemical intrinsic in vacuo potentials for prediction of conformations in solution [O. Sinano?lu, in The World of Quantum Chemistry, R. Daudel and B. Pullman, Eds. (Reidel, Dordrecht, 1974)]. There have also been some recent applications that illustrate the convenience of our solvophobic theory in correcting for solvent effects once quantum-mechanical molecular electronic structures and potential-energy surfaces are computed.     

Empirical Model of Solvophobic Interactions in Organic Solvents

An empirical model was developed to predict organic solvophobic effects using N-phenylimide molecular balances functionalized with non-polar alkyl groups. Solution studies and X-ray crystallography confirmed intramolecular alkyl-alkyl interactions in their folded conformers. The structural modularity of the balances allowed systematic variation of alkyl group lengths. Control balances were instrumental in isolating weak organic solvophobic effects by eliminating framework solvent-solute effects. A ¹⁹F NMR label enabled analysis across 46 deuterated and non-deuterated solvent systems. Linear correlations were observed between organic solvophobic effects and solvent cohesive energy density (ced) as well as changes in solvent-accessible surface areas (SASA). Using these empirical relationships, a model was constructed to predict organic solvophobic interaction energy per unit area for any organic solvent with known ced values. The predicted interaction energies aligned with recent organic solvophobic measurements and literature values for the hydrophobic effect on non-polar surfaces confirmed the model‘s accuracy and utility.     

Implicit solvent models for micellization of ionic surfactants

We propose a method for parametrization of implicit solvent models for the simulation of the self-assembly of ionic surfactants into micelles. The parametrization is carried out in two steps. The first step involves atomistic molecular dynamics simulations of headgroups and counterions with explicit solvent to determine structural properties. An implicit solvent model of the headgroup/counterion system is obtained by matching structural quantities between explicit solvent and implicit solvent systems. In the second step, we identify the solvophobic attractions between the tail beads. We determine the solvophobic parameters using grand canonical Monte Carlo simulations with histogram reweighting techniques. The matching objective for the identification of solvophobic attractions is the critical micelle concentration (cmc). We choose sodium dodecyl sulfate as the reference system. On the basis of hydrophobic parameters obtained from this particular model, we study specific ion effects (lithium and potassium instead of sodium) as well as the effect of cationic headgroups (dodecyltrimethylammonium bromide/chloride). Furthermore, the chain length dependence of micellization properties is investigated for sodium alkyl sulfate, with alkyl lengths between 6 and 14. All cases considered give results in broad agreement with experimental data, confirming the transferability of parameters and the generality of the approach.     

Concentration effects on distribution of macromolecules in small pores

The interactions between two particles and between one particle and a rigid boundary are examined to study the effect of particle concentration on partitioning, stress and flow in microporous media. Because the particle—particle and particle—wall interactions occur over comparable length scales, their effects are not additive and lead to non-uniform particle concentration stress (“surface pressure”) in the vicinity of the boundary. A particle concentration gradient parallel to the boundary creates a gradient in surface pressure which drives a viscous flow of the solvent toward regions of higher concentration. Such flows are termed “osmosis”, and the effect of particle interactions is to reduce the osmotic velocity.     

Nanostructure and amphiphile self-assembly in polar molecular solvents: amides and the "solvophobic effect"

The ability of low molecular weight amides to support amphiphile self-assembly is shown to be a general feature for this class of solvents. This report extends the number of known polar solvents which can support amphiphile self-assembly by five new amides; more than doubling the number of known amides able to serve as amphiphile self-assembly media. The formation of lyotropic liquid crystalline phases by cationic and non-ionic surfactants in these liquid amides is reported. The ability of a solvent to promote amphiphile self-assembly is governed by the "solvophobic effect" and is linked to the solvent cohesiveness. The Gordon parameter which is a measure of the solvent cohesiveness was found to provide a guide to an amides capacity to support lyotropic liquid crystalline phase diversity and thermal stability ranges of those phases. The "solvophobic effect" and steric hindrance factors were compared between amide's and protic ionic liquids possessing analogous chemical structures and also being able to promote amphiphile self-assembly.     

The solvent dimethyl sulfoxide

The dipolar aprotic solvent dimethyl sulfoxide is liquid over a wide range of temperatures, is a strong electron donor, and has a high polarity. It is therefore an excellent and selective solvent for many organic and even polymeric compounds, and can enter into H-bonding and dipole-dipole association. The structure of dimethyl sulfoxide, with a “hard” oxygen atom and a “soft” sulfur atom, leads to good solvation of cations and poor solvation of anions. Mixtures of alkoxides with dimethyl sulfoxide are therefore among the most strongly basic systems in organic chemistry, and are excellently suited for the deprotonation of weakly acidic OH, NH, and CH bonds, for eliminations, and for the initiation of polymerizations.     

Solvent phase behavior and the interaction of uniform and patterned solutes

Isotropic and anisotropic hypernetted-chain (HNC) integral equation theories are used to obtain the interaction of solutes both near and far from the solvent liquid-vapor coexistence. Spherically symmetrical and chemically patterned (patched) solutes are considered, and the influences of particle and patch sizes are investigated. Solvophilic and solvophobic solutes (or patches) are examined. Near coexistence, in the solvophobic case drying-like behavior occurs for solutes (patches) of sufficient size. This gives rise to relatively long ranged attractive forces that are strongly orientation dependent for the patched solute particles. We also report grand canonical Monte Carlo results for a pair of spherically symmetric solutes. This demonstrates that the anisotropic HNC theory gives qualitatively correct solvent structure in the vicinity of the solutes. Comparison with previous simulations also shows that the solute-solute potentials of mean force given by the anisotropic theory are more accurate (particularly at small separations) than those obtained using the isotropic method.     

Cocatalysis in Cationic Polymerization

Problems concerned with the principles of cocatalysis and coinitiation as a part of cationic polymerization are discussed. When the established concept of different reactive particles, i.e., contact and separated ion-pairs or free ions, is applied to cationic initiation and propagation centers, then common features for one general process can be drawn even in so diverse cases as “pseudocationic” polymerization, solvent “cocatalysis,” polymerization during condensation and induced by co-monomer addition. A special case of activation by solvent is “cocatalysis” by water.

The model for these cases was found during the interpretation of waves observed on styrene polymerization curves. The formation of ion-pairs proceeds spontaneously. The activation and deactivation of these ion-pairs is effected via coordination of suitable molecules with the former, i.e., by equilibrium shifts     

Role of the solvophobic effect on micellization

Experimental data of amphiphiles aggregation phenomena in water-organic solvent mixtures were considered with the idea of investigating the role of the solvophobic effect on micellization. Changes in the critical micelle concentration, in the micellar ionization degree (for ionic surfactants) and in the aggregation number accompanying variations in the composition of the bulk phase of the micellar solutions were examined with the scope of understanding which properties of the water-organic solvent mixtures are important in the micellization process. Results point out that the cohesive energy density, measured either through the Hildebrand-Hansen solubility parameter or the Gordon parameter, seems to play an important role in determining the contribution of the solvophobic effect on the Gibbs energy of micellization in water-organic solvents mixtures.     

The C-potential surface for predicting conformations of molecules in solution

A new “C-potential” C(R _m ) for predictions of conformations, relative stabilities of isomers, transition states, of a molecule M in solution as a function of its geometry R _m is given. The potential includes all the solvent effects including the “solvophobic force” given earlier by the writer with parameters fully specified in terms of simple handbook properties of liquids. It is proved that C(R _m ) can be used in statistical mechanical equations for equilibria and for activated complex rates just as though it were an ordinary potential energy surface dependent on R _m only.     

Solvent effects on the 9-hydroxymethylanthracene + N-ethylmaleimide Diels-Alder reaction. A theoretical study

[structure: see text] The origin of the high reaction rates of the 9-hydroxymethylanthracene + N-ethylmaleimide Diels-Alder reaction in fluorous solvents and supercritical carbon dioxide is analyzed through a combination of regression analyses and theoretical calculations. Both approaches allow the solvent effects on the activation barrier (a decrease by solvophobic interactions, an increase by dipolarity-polarizability) to be attributed to the existence of a hydrogen bond between the two reactants in the transition state, refuting a previous hypothesis based on strong solvophobic interactions.     

The coalescence of polystyrene in correlated binary solvents

The solution behavior of solvophobic polymers is crucial to the development of polymer coatings and polymeric drug delivery vehicles. In this article, the role of dipolar interactions is investigated in the solvophobic coalescence of polystyrene in binary correlated polar solvent mixtures. A simple model for coalescence thermodynamics is derived from correlations between thermally rotating dipole moments in the solvent. The stabilizing correlations lost to the solvent due to a solute's presence give rise to a driving force for the coalescence of solutes. This stabilization is offset by the entropy of mixing that favors the dispersion of solutes. Predictions are compared to the measured point of coalescence of polystyrene in acetone when different alcohols are titrated. The model is shown to capture this point of coalescence and conformation for a variety of systems. Our results suggest the significant property determining the solubility of nonpolar polymers in a polar liquid is a free energy resulting from attractive dispersion interactions between thermally rotating solvent dipole moments. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 948–955     

The infinite dilution short-range and long-range activity coefficient of ions in a solvent of polarizable hard spheres

The infinite dilution activity coefficient of ions in a solvent of polarizable hard spheres is divided into two parts: short range and long range. The ions are treated as hard spheres with point charges and the solvent molecules are treated as polarizable hard spheres. The diameters of ions may be different than the diameter of polarizable particles.     

Understanding the role of near-surface solvent in electrochemical adsorption and electrocatalysis with theory and experiment

Predictive (electro)catalyst and electrode design requires a quantitative understanding of the effect of solvent close to the catalyst or electrode surface. Complicating a fundamental understanding of this “near-surface” solvent is that while solvent behavior in “bulk” solution far from a surface is fairly well understood, evidence from both experiment and theory suggests the behavior of many solvents close to a surface is different from that of the solvent far away. In this perspective, we will review how ab initio computational modeling can be directly compared to detailed experimental measurements to quantitatively understand the effects of this near-surface solvent. From this quantitative comparison, the various approximations which have been developed to treat the behavior of near-surface solvent can be benchmarked and rules for their use or improved modeling methodologies can be developed.     

Synthesis and magnetic properties of the exchange-coupled SrFe10.7Al1.3O19/Co composite

The magnetic composite SrFe_10.7A_l1.3O₁₉/Co was synthesized by ethylene glycol reduction of cobalt ions on the surface of hexaferrite particles dispersed in the solvent. The resulting material contained magnetically hard submicron hexaferrite particles covered by soft magnetic cobalt nanoparticles. The composite demonstrated the exchange-coupling effect between hard and soft magnetic phases.     

Aggregation of flexible-rigid-flexible triblock copolymers

We discuss the aggregation behavior of flexible-rigidflexible triblock copolymers in a selective solvent of low molecular weight. Aggregation may lead either to plates of (R) covered by brushes of (F), or to large “needles” (as a consequence of the Skoulios effect). In the absence of anisotropic bonding between adjacent rods, the “fence” morphology is not expected.     

Strongly stretched polymer brushes

Polymer “brushes” are formed when long-chain molecules are somehow attached by one end at an interface with a relatively small area per chain. Such adsorbed brushes in the presence of solvent may be used to modify surface properties, stabilize colloidal particles, etc. Strongly segregated block copolymer phases, or interfacial layers of such “polymeric surfactants” may also be modeled in terms of “melt brushes,” (i.e., brushes without solvent). In both cases, when chain attachments are crowded on the interface, the chains stretch out to avoid neighboring chains. The resulting physical state has properties markedly different from polymer solutions, gels, or weakly adsorbed polymer layers. When the chains are strongly stretched, their statistical mechanics become simpler, as fluctuations around the set of most probable conformations are suppressed. This makes possible many pencil-and-paper calculations of brush properties, including bending and compressional moduli, and detailed knowledge of the chain conformations. As a recent example, I will describe calculations of phase diagrams of strongly segregated block copolymers including bicontinuous double-diamond phases. © 1994 John Wiley & Sons, Inc.     

Nanosegregated polymeric domains on the surface of Fe3O4@SiO2 particles

Multifunctional, biocompatible, and brush‐grafted poly(ethylene glycol)/poly(ε‐caprolactone) (PEG/PCL) nanoparticles have been synthesized, characterized, and used as vehicles for transporting hydrophobic substances in water. For anchoring the polymer mixed brushes, we used magnetic‐silica particles of 40 nm diameter produced by the reverse microemulsion method. The surface of the silica particle was functionalized with biocompatible polymer brushes, which were synthesized by the combination of “grafting to” and “grafting from” techniques. PEG was immobilized on the particles surface, by “grafting to,” whereas PCL was growth by ROP using the “grafting from” approach. By varying the synthetic conditions, it was possible to control the amount of PCL anchored on the surface of the nanoparticles and consequently the PEG/PCL ratio, which is a vital parameter connected with the arrangement of the polymer brushes as well as the hydrophobic/hydrophilic balance of the particles. Thus, adjusting the PEG/PCL ratio, it was possible to obtain a system formed by PEG and PCL chains grafted on the particle's surface that collapsed in segregated domains depending on the solvent used. For instance, the nanoparticles are colloidally stable in water due to the PEG domains and at the same time are able to transport, entrapped within the PCL portion, highly water‐insoluble drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2966–2975