Insight into the enantioselective of chiral penthiopyrad for serum albumin: Spectroscopic and computational approaches

Chiral pesticides, such as penthiopyrad, consist of enantiomers with differing biological activities and toxicological profiles, potentially leading to environmental risks. This study investigates the stereoselective binding of the R-(−)- and S-(+)-enantiomers of penthiopyrad to bovine and human serum albumin (BSA/HSA) using a combination of spectroscopic techniques, density functional theory (DFT) calculations, and molecular docking. The results indicate that S-(+)-penthiopyrad exhibits a significantly stronger quenching effect on the intrinsic fluorescence of both HSA and BSA than R-(−)-penthiopyrad, suggesting a higher binding affinity, which is consistent with DFT predictions. Specifically, the binding constants (ΔG) of S-(+)-penthiopyrad with BSA and HSA were −31.80 kJ/mol and −35.68 kJ/mol, respectively, compared to −30.42 kJ/mol and −33.82 kJ/mol for R-(−)-penthiopyrad. Circular dichroism (CD) spectroscopy and FTIR analysis show that both enantiomers induce conformational changes in albumin secondary structures, reducing α-helical content by 3.6 % for S-(+)-penthiopyrad and 2.1 % for R-(−)-penthiopyrad in BSA, and by 2.7 % and 0.2 %, respectively, in HSA. Molecular docking identifies site II (subdomain IIIA) as the primary binding region, with hydrogen bonding and hydrophobic interactions stabilizing the S-(+)-penthiopyrad complex more effectively. These findings underscore the higher environmental risk of S-(+)-penthiopyrad compared to R-(−)-penthiopyrad, advancing the molecular-level understanding of stereoselective behavior in chiral fungicides and guiding safer agrochemical development.