Universal Model Based on the Mobile Order and Disorder Theory for Predicting Lipophilicity and Partition Coefficients in All Mutually Immiscible Two-Phase Liquid Systems

Abstract

The quantitative thermodynamic development of the mobile order and disorder theory in H-bonded liquids has been extended in order to predict partition coefficients. The model enables "a priori" estimation of the partition coefficient (log P) of neutral solutes, not only in the conventional 1-octanol/water reference but also in all mutually saturated two-phase systems made up of largely immiscible solvents. The model is obtained from the thermodynamic treatment of the various physicochemical free energy processes encoded in the overall distribution process and accordingly provides a useful tool for better understanding both the origin and the factors, such as the solute molar volume, that determine the partition coefficient of nonelectrolytes in a given system. From the comparison of the relative magnitude of the processes contributing to the log P value, a lot of information can also be gained regarding the variation in log P of the same substance partitioned between different solvent systems. As a demonstration, the model has been successfully applied to predict the log P of a great number of chemicals of varying structure, size, and chemical nature partitioned in a large set of essentially immiscible solvent pairs, differing either by their nonpolar or by their polar phase. In the systems involving water as the polar phase, the hydrophobic effect is always the driving force that governs the distribution process irrespective of the interacting or noninteracting nature of the substances studied. In the other two-phase systems, the partitioning of complexing solutes in particular appears to be ruled rather by their hydrogen-bonding capabilities than by their hydrophobicities.

Anisotropic Solvent Model of the Lipid Bilayer. 1. Parameterization of Long-Range Electrostatics and First Solvation Shell Effects

“…It should be universal to allow calculating transfer energy from water or vapor to any liquid phase 10–12 . It should be physics-based to describe all essential components of free energy, including hydrophobic interactions, solute-solvent hydrogen bonds and long-range electrostatics.…”

Unified Physicochemical QSPR Model of the Partitioning and Solubility of Chemicals in the Triple System “Water–Octanol–Air”

“…In this part, the approach does not differ fundamentally from the MOD model [4], the "solvation equation" [5,6], and the CODESSA approach [1 -3]. The essential difference of our approach is based on the way of application of regression equations.…”

“…Therefore, QSPR models based on a limited (but sufficient) number of physicochemical and especially thermodynamic descriptors with a clear physical meaning are much more valuable than formal models with good statistical criteria. For twophase systems such models are available as for instance in the publications of Ruelle [4] and Abraham [5].…”

Estimation of alkane–water logP for neutral, acidic, and basic compounds using an alkylated polystyrene-divinylbenzene high-performance liquid chromatography column

“…A set of structurally diverse solutes (n = 76) comprised of neutral and ionizable acidic and basic compounds was chosen to characterize the gradient and isocratic systems, and data for isocratic log k 50 and gradient t R are reported (Table 1). For most of these compounds (n = 62), reference log P alk values were available from the literature [1,4,[6][7][8]16,[27][28][29][30][31][32][33][34][35], based on shake-flask assays, dual-phase potentiometric titration, water and alkane phase gaseous solubility ratios, or similar experimental methods (Table 1).…”

“…As an alternative, hydrocarbons better emulate microenvironments such as the interior of the lipid bilayer [2,3]. Accordingly, there is growing interest in the use of alkane-water log P as an additional lipophilicity descriptor [4][5][6][7][8][9][10]. Heptane-water and hexadecane-water are two of the more commonly used partition systems.…”