Theoretical and Experimental Studies on Partitions of γ-Substituted Butyric Acids in Chloroform/Water and Dichloromethane/Water Systems

Abstract

Having measured the log P value of γ-hydroxybutyric acid (GHB) in chloroform/water and dichloromethane/water systems at T = 25 and 37 °C, the relative log P value for the structural analogue γ-aminobutyric acid (GABA), log P (GABA) − log P (GHB), has been determined theoretically. A combined ab initio/Monte Carlo method for obtaining the internal free energy and the relative solvation free energy, respectively, has been applied for studying the conformational/tautomeric equilibria of GABA in the three solvents. Free energy changes for the partition processes have been calculated within thermodynamic cycles. There is no significant difference in the log P values for the neutral GABA and GHB of −1.22 ± 0.12 at 37 °C, as measured in the chloroform/water system. Using the more polar dichloromethane solvent as the organic phase, the GABA log P increases compared to its log P in chloroform. Because GABA almost entirely takes the zwitterionic form in aqueous solution, it is a key question whether this tautomeric...