Probing the Molecular Interaction of Triazole Fungicides with Human Serum Albumin by Multispectroscopic Techniques and Molecular Modeling

Abstract

Triazole fungicides, one category of broad-spectrum fungicides, are widely applied in agriculture and medicine. The extensive use leads to many residues and casts potential detrimental effects on aquatic ecosystems and human health. After exposure of the human body, triazole fungicides may penetrate into the bloodstream and interact with plasma proteins. Whether they could have an impact on the structure and function of proteins is still poorly understood. By using multispectroscopic techniques and molecular modeling, the interaction of several typical triazole fungicides with human serum albumin (HSA), the major plasma protein, was investigated. The steady-state and time-resolved fluorescence spectra manifested that static type, due to complex formation, was the dominant mechanism for fluorescence quenching. Structurally related binding modes speculated by thermodynamic parameters agreed with the prediction of molecular modeling. For triadimefon, hydrogen bonding with Arg-218 and Arg-222 played an important role, whereas for imazalil, myclobutanil, and penconazole, the binding process was mainly contributed by hydrophobic and electrostatic interactions. Via alterations in three-dimensional fluorescence and circular dichroism spectral properties, it was concluded that triazoles could induce slight conformational and some microenvironmental changes of HSA. It is anticipated that these data can provide some information for possible toxicity risk of triazole fungicides to human health and be helpful in reinforcing the supervision of food safety