Thermodynamic characterization of the binding process of sulindac to human serum albumin.

Abstract

This study deals with the molecular basis of the binding of the anti-inflammatory drug sulindac (CAS 38194-50-2) to human serum albumin (HSA) using high-performance liquid affinity chromatography. The chromatography was carried out using a HSA-immobilized column and a predominantly aqueous mobile phase (67 mmol/l sodium phosphate buffer/propan-1-ol, 94:6 v/v). A small quantity of sulidac was injected onto the column while increasing concentrations of the same drug were added to the mobile phase. The capacity factor k' serves as a measure for the binding affinity. The experiments were carried out at different temperatures in order to establish some thermodynamic parameters of the binding process. The values of the binding affinity constants decreased with the temperature. The free energy change was almost constant. Its large negative value suggests a spontaneous binding of sulidac to HSA. Both enthalpy and entropy changes of the binding process were also negative assuming donor-acceptor interactions between sulindac and its binding sites in HSA. Hydrogen bonds and salt linkages are supposed to make a major contribution to the binding of sulindac to HSA, while hydrophobic interactions seem to be of less importance.