Site-Selective Interaction of Human Serum Albumin with 4-Chloro-7-nitro-1,2,3-benzoxadiazole Modified Olanzapine Derivative and Effect of β-Cyclodextrin on Binding: In the Light of Spectroscopy and Molecular Docking.

Here, we present a detailed investigation on the interaction of 4-chloro-7-nitro-1,2,3-benzoxadiazole (NBD) embedded olanzapine derivative (OLA-NBD) with a model transport protein, human serum albumin (HSA). The thermodynamic parameters, Δ H o , Δ S o , and Δ G o , as evaluated by considering the van't Hoff relationship imply the major contribution of electrostatic/ionic interactions for the HSA-OLA-NBD association. The OLA-NBD induced quenching of HSA emission occurs through static quenching mechanism, indicating a 1:1 association, as portrayed from Benesi-Hildebrand plot, with ∼10 4 M -1 association constant value, and it is in good harmony with the value estimated from anisotropy experiment. The invariance of the time-resolved decay behavior of HSA with added OLA-NBD concentration, along with matching dependency of the binding constant ( K b ) value on temperature, also supports the occurrence of static quenching. The effect of β-cyclodextrin on HSA-OLA-NBD binding is characterized by a smaller K b value revealing that the OLA-NBD molecules are gradually removed from β-CD by HSA to achieve its medicinal outcome of drug delivery. The outcome from circular dichroism (CD) illustrates the variation of HSA secondary structure upon interaction with OLA-NBD. Concurrently, HSA-OLA-NBD association kinetics is also explored by applying the fluorescence technique. The possible interaction zone of OLA-NBD in HSA is investigated from AutoDock-based docking simulation study.