HSA-SOLUTE INTERACTIONS, ENANTIOSELECTIVITY, AND BINDING-SITE GEOMETRICAL CHARACTERISTICS

Recently, a theoretical model was proposed to study the existence of p ockets of acetonitrile (ACN) called clusters in a hydroorganic mixture . The proposal used ACN as an interaction organic modifier between D,L -dansyl amino acids and their binding site in human serum albumin at s ite II. This solute binding is governed by primary and secondary inter actions. The primary interactions are under the dependence of the solu te solvation by ACN clusters and electrostatic interactions. Following this first step, the solute engages strong short-range interactions w ith the residues of site II. Using a biochromatographic approach, the solute binding, i.e., the solute retention, was divided into two diele ctric constant (epsilon) ranges. In the first range, epsilon > epsilon (c) (epsilon(c) is the critical dielectric constant); the primary and secondary nonstereoselective electrostatic interactions were the major contributions to the variation in the solute binding with the ACN fra ction in the mixture. In the second range, epsilon < epsilon(c), the s olute retention variation with the ACN fraction was governed by its so lvation by the ACN clusters and also by the secondary hydrophobic ster eoselective interaction. The mathematical model developed provided the determination of the surface charge density of site II as well as the cluster number that solvates each solute.