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 into 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 complex of protein-ligand 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 consider introducing hydroxyl or bromine.

羟基和溴是重要的官能团，经常被引入活性化合物（如药物和农药）的分子结构中。为了研究它们的蛋白质结合特性的差异，选择了2-羟基苯并噻唑（HOB）和2-溴苯并噻唑（BRB）作为与人血清白蛋白（HSA）相互作用的配体。通过多光谱检测破译了相互作用的平衡。热力学参数表明，识别是由典型的疏水力导致的自发和熵驱动过程。通过同步发射光谱和圆二色性技术检查了HSA的构象变化。结合位点通过荧光探针策略确认。通过分子对接法确定了新的蛋白质-配体复合物的结构，其中涉及氢键以及HOB和BRB的分子取向。系统地比较了HOB和BRB的白蛋白结合细节，并通过密度泛函理论（DFT）分析尝试解释了能量转移效率和亲和力的差异。该研究有望为合理设计含有苯并噻唑支架的新型药物或农药提供指导，尤其是考虑引入羟基或溴时。