A binuclear Cu(I)-phosphine complex as a specific HSA site I binder: synthesis, X-ray structure determination, and a...

In this research, we present a method for synthesis and a detailed description of geometry characterization of a novel binuclear Cu(I) phosphine complex, along with analysis of its interaction with HSA using spectroscopic and simulation methods. The Cu atoms are coordinated in a tetrahedral geometry, which results in coordination by two nitrogen atoms from the N,N'-(ethane-1,2-diyl)bis(1-(pyridin-2-yl)methanimine ligand (L), a chloride, and a PPh₃. The complex binding constant to HSA in a biochemical environment was determined to be ∼10⁶, which is indicative of a strong interaction. The fluorescence of HSA is significantly quenched by binding to the complex via a static mechanism, whereas the microenvironment of the tryptophan residue remains unchanged. A spontaneous binding process was indicated by a negative value for ΔG. Thermodynamic signatures reflect the dominance of hydrophobic forces during the interaction. The site marker competitive experiment combined with docking simulation analysis revealed the closeness position of the complex binding site to warfarin location in specific ligand site I of HSA. The information generated in the present study would be valuable to understand the interaction mechanistic and pharmacological behavior of Cu(I) complexes.Communicated by Ramaswamy H. Sarma.