‘Biophysical and computational elucidation of the intermolecular Bendiocarb-BSA interaction at site I: structural and dynamic perspectives’

Bendiocarb (BEN), a carbamate insecticide designated as moderately hazardous (Class II) by the WHO (2009), is extensively utilized in agricultural and residential pest control, raising significant concerns about its toxicological and environmental impacts. BEN has been identified in pregnant women exposed to domestic pest-control methods, indicating possible human exposure. Owing to its lipophilicity and ecological persistence, BEN presents toxicological hazards through bioaccumulation and interactions with plasma proteins. Nonetheless, the molecular-level understanding of its interaction with serum proteins remains limited. Here, an integrative strategy that incorporates multispectroscopic and computational approaches was used to investigate the binding mechanism, structural perturbations, and dynamic behavior of BEN in interaction with BSA, a model transport protein. Spectroscopic investigations demonstrated efficient quenching of BSA intrinsic fluorescence via a static mechanism, indicating the development of a stable ground-state complex and minor but measurable conformational perturbations upon binding. The experimentally determined binding constant value (Kb ≈ 102) signifies a moderate binding affinity between BEN and BSA, aligning with the documented toxicokinetic profile of BEN as a moderately hazardous pesticide (WHO Class II). Docking and 100 ns MD simulations showed that BEN preferentially binds to Site I of BSA, generating a stable complex. Complementarily, DFT and MM/GBSA investigations indicated a narrow HOMO–LUMO gap and a favorable binding free energy (ΔGbind of −9.21 kcal·mol−1), implying moderate chemical reactivity and a thermodynamically stable BEN–BSA interaction. These findings improve understanding of BEN’s bioavailability, and toxicokinetics, providing a significant foundation for environmental risk evaluation and the development of safer pesticide alternatives.