Insights into Platinum Complex-HSA Bindings: Spectral and Molecular Dynamics Simulation Studies

Document Type : Regular Article


1 Department of Chemistry, Shiraz University of Technology, Shiraz 71555-313, Iran

2 Protein Chemistry Laboratory (PCL), Department of Biology, Shiraz University, Shiraz 71454, Iran

3 Department of Chemistry, Shahid Beheshti University, Evin, Tehran 19839-69411, Iran

4 Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran



Mutual interactions of human serum albumin (HSA) with the two binuclear platinum complexes, containing [(bhq)Pt(dppm)2(Cl)Pt(bhq)(Cl)] (1) and [(bhq)Pt(dppm)2(PhMe)Pt(bhq)(CO2CF3)] (2), in which bhq=benzo[h]quinoline, and dppm=bis(diphenylphosphino) methane, were thoroughly investigated using spectroscopic and molecular modeling techniques. In this respect, fluorescence, Ultraviolet-Visible (UV-Vis) and circular dichroism (CD) spectroscopies, along with the docking and molecular dynamics simulations (MD) were utilized.
Analysis of spectroscopic and MD simulation results revealed the structural alterations of HSA, upon binding to the binuclear platinum complexes, while the hydrogen bonding and van der Waals forces were found to mainly contribute to the protein-ligand intermolecular interactions. Results of far-UV CD measurements showed the strong ability of platinum complexes, in reducing the α-helical content of HSA, while other secondary structural features were increased.
Due to their different chemical natures, these complexes bind to HSA in different manners. Binding constants and thermodynamic binding parameters between these complexes and HSA were calculated using the Stern−Volmer and van’t Hoff equations. Calculated thermodynamic binding parameters indicated that the interaction is spontaneous and enthalpy driven, through the static and dynamic quenching mechanisms, for complexes 1 and 2, respectively.

Graphical Abstract

Insights into Platinum Complex-HSA Bindings: Spectral and Molecular Dynamics Simulation Studies