Investigations on the pH-dependent binding of sodium valproate with bovine serum albumin: A calorimetric, spectroscopic and volumetric approach

Abstract

The present study reports the binding behaviour of sodium valproate (SV) with bovine serum albumin (BSA) at different temperatures and pH (5.8, 7.4 and 8.0) of the medium using calorimetry, spectroscopy (UV–visible absorption, 1H NMR) and volumetry (density and sound velocity). Calorimetric results indicate the involvement of electrostatic, hydrogen bonding and van der Waals interactions in the binding process. The decrease in binding constant (K) and increase in the burial of hydrophobic groups of BSA upon SV binding has been observed from calorimetry with increase in pH from 5.8 to 8.0. The absorption measurements revealed the formation of ground state complex with 1:1 stoichiometry of binding as well as no change in the microenvironment around the amino acid residues of BSA after binding with SV. The broadening of the 1H NMR signals of the protons of SV upon binding with BSA has also been observed. The larger polar interactions/dehydration phenomenon at lower whereas non-polar interactions/ hydrational phenomenon at higher SV concentrations for SV-BSA binding have been noticed from the variation of trends of V, E°, and Ks values with drug concentrations as well as with temperature at all the studied pH values of the medium.