Unraveling the binding interactions between two Pt(II) complexes of aliphatic glycine derivatives with human serum albumin: A comprehensive computational and multi-spectral investigation

This article delves into the interaction between HSA protein and synthesized platinum complexes, with formula: [Pt(Propyl-NH2)2(Propylglycine)]NO3 and [Pt(Tertpentyl-NH2)2(Tertpentylglycine)]NO3, through a range of methods, including spectroscopic (UV–visible, fluorescence, synchronous fluorescence and CD) analysis and computational modeling (molecular docking and MD simulation). The binding constants, the number of binding sites, and thermodynamic parameters were obtained at 25 to 37 °C. The study found that both complexes could bind with HSA (moderate affinity for Tertpentyl and strong affinity for Propyl derivatives) and occupied one binding site in HSA (validated with, Stern-Volmer, Job-plots, and molecular docking investigations) located in subdomain IIA. The binding mechanisms of both mentioned Pt(II) agents were different, with the Propyl derivative predominantly using van der Waals forces and hydrogen bond interactions with a static quenching mechanism and the Tertpentyl derivative mainly utilizing hydrophobic force with a dynamic quenching mechanism. However, the two ligands affected protein differently; the Tertpentyl complex did not significantly alter the protein structure upon binding, as evidenced by synchronous fluorescence spectroscopy (SFS), CD spectroscopy, and MD analysis. The outcome helps in understanding the binding mechanisms and structural modifications induced by the ligands, which could aid in the innovation of more effective and stable Pt(II)-based drugs.