Insights from a combination of theoretical and experimental methods for probing the biomolecular interactions between human serum albumin and clomiphene.

In this study, the interaction of clomiphene (CLO), a non-steroidal and ovulatory stimulant drug employed in the treatment of infertility, with human serum albumin (HSA), the most abundant plasma transport protein, was investigated using spectrofluorometric, FT-IR, UV-Vis, and molecular modeling methods. The obtained results indicated that the binding of CLO to HSA led to intense fluorescence quenching of HSA via a static quenching mechanism, and that the process of CLO binding to HSA was enthalpy driven. By using experimental and theoretical methods, it was confirmed that as a result of binding CLO, slight conformational changes in HSA occurred. Also, the negative Δ H of interaction indicated that the binding of CLO with HSA was mainly enthalpy driven. The experimental and computational results suggested that hydrogen bonds and van der Waals interactions played a major role in the binding, with overall binding constants of K = 3.67 × 10 9 M -1 at 286 K and 6.52 × 10 5 mol L -1 at 310 K. Moreover, the results of molecular modeling showed that Asp234, Phe228, Leu327, and Arg209 in HSA had the highest interaction energies with the ligand.