Albumin-binding difference caused by hydroxy and bromo on position-2 of benzothiazole

Abstract

Hydroxyl and bromine are important function groups which have been frequently introduced into the molecular structures of active compounds like drugs and pesticides. To investigate the difference of their protein-binding properties, 2-hydroxybenzothiazole (HOB) and 2-bromobenzothiazole (BRB) were selected as ligands to interact with human serum albumin (HSA). The interaction equilibriums were deciphered by multi-spectroscopic detections. Thermodynamic parameters manifested that the recognitions were spontaneous and entropy-driven processes leading by typical hydrophobic forces. The conformational change of HSA was inspected by synchronous emission spectra and circular dichroism techniques. The binding site was confirmed by fluorescence probe strategy. The structure of new protein–ligand complexes was ascertained by molecular docking method, in which the hydrogen bonds as well as molecular orientation of HOB and BRB were involved. The albumin-binding details of HOB and BRB were compared systematically and the difference in energy transfer efficiency and affinity was tentatively explained by density functional theory (DFT) analyses. The study is expected to provide guidance for rational design of novel drugs or pesticides containing benzothiazole scaffold, especially when considering introducing hydroxyl or bromine.