The chemical interpretation and practice of linear solvation energy relationships in chromatography

This review focuses on the use of linear solvation energy relationships (LSERs) to understand the types and relative strength of the chemical interactions that control retention and selectivity in the various modes of chromatography ranging from gas chromatography to reversed phase and micellar electrokinetic capillary chromatography. The most recent, widely accepted symbolic representation of the LSER model, as proposed by Abraham, is given by the equation SP = c + e E + s S + a A + b B + v V in which, SP can be any free energy related property. In chromatography, SP is most often taken as log k′ where k′ is the retention factor. The letters E, S, A, B, and V denote solute dependent input parameters that come from scales related to a soluteʹs polarizability, dipolarity (with some contribution from polarizability), hydrogen bond donating ability, hydrogen bond accepting ability, and molecular size, respectively. The e-, s-, a-, b-, and v -coefficients and the constant, c, are determined via multiparameter linear least squares regression analysis of a data set comprised of solutes with known E, S, A, B, and V values and which span a reasonably wide range in interaction abilities. Thus, LSERs are designed to probe the type and relative importance of the interactions that govern solute retention. In this review, we include a synopsis of the various solvent and solute scales in common use in chromatography. More importantly, we emphasize the development and physico-chemical basis of – and thus meaning of – the solute parameters. After establishing the meaning of the parameters, we discuss their use in LSERs as applied to understanding the intermolecular interactions governing various gas–liquid and liquid–liquid phase equilibria. The gas–liquid partition process is modeled as the sum of an endoergic cavity formation/solvent reorganization process and exoergic solute–solvent attractive forces, whereas the partitioning of a solute between two solvents is thermodynamically equivalent to the difference in two gas/liquid solution processes. We end with a set of recommendations and advisories for conducting LSER studies, stressing the proper chemical and statistical application of the methodology. We intend that these recommendations serve as a guide for future studies involving the execution, statistical evaluation, and chemical interpretation of LSERs.