Interaction of haloperidol with human serum albumin and effect of metal ions on the binding

Abstract

The interaction between human serum albumin (HSA) and haloperidol (HPD) was studied by fluorescence and absorption spectroscopy and molecular modeling under physiological conditions. Fluorescence spectroscopic data showed that the fluorescence quenching of HSA was a result of the formation of the HPD–HSA complex. Spectroscopic analysis of the emission quenching at different temperatures revealed that the quenching mechanism of human serum albumin by haloperidol shows a dynamic quenching. The binding constant (K) and the binding sites (n) between haloperidol and HSA were estimated to be 7.94 × 103 dm3 mol−1 and 1.12 at 298 K. The results of thermodynamic parameters, ΔH (− 89.56 kJ mol−1), ΔS (225.94 J mol−1 K−1) and ΔG (− 15.69 kJ mol−1), indicated that the binding process was spontaneous and the van der Waals interactions and hydrogen bonds were the main forces to stabilize the complex. The distance between the donor (HSA) and acceptor (HPD) molecules was obtained according to Förster energy transfer. The effects of metal ions (Ca2+, Mg2+, Cu2+, and Fe3+) on the binding constant of the haloperidol–HSA complex were also investigated. Finally, the binding of haloperidol to HSA was modeled using the molecular docking method. Molecular docking results were in agreement with the experimental conclusions of the thermodynamic parameters.