Comparative study of an osazone based ligand and its palladium(II) complex with human serum albumin: A spectroscopic, thermodynamic and molecular docking approach

Abstract

An osazone based ligand, hexane-3,4-dione-bis(2'-phenylhydrazone) (LH₂), was synthesized by 1:2M Schiff base condensation of 3,4-hexanedione and phenylhydrazine in dehydrated methanol. Its palladium(II) complex (1) has also been synthesized. LH₂ and 1 have thoroughly been characterized by several spectroscopic and analytical means. DFT optimized structure of 1 shows that it is a monomeric Pd(II) complex having 'N₂Cl₂' coordination chromophore. Our BVS analysis also satisfactorily reproduces the oxidation number of the palladium center. 1 shows irreversible Pd(II)/Pd(I) reduction in its CV in methanol. 1 is three-fold more emissive than LH₂. This enhanced emission has also been supported by time correlated single photon counting (TCSPC) measurements at room temperature. Human serum albumin (HSA) binding aspects of both LH₂ and 1 have been investigated through various biophysical techniques. The binding constants as determined from Benesi-Hilderbrand plot using the absorbance spectral analyses were found respectively to be 1.18×10⁵ and 4.38×10⁴M^-1 for LH₂ and 1. The experimental findings confirm that both are good HSA binders. The thermodynamic parameters (∆G°, ∆H° and ∆S°) have also been evaluated by isothermal titration calorimetric (ITC) experiments. These parameters indicate that the binding processes are spontaneous both for LH₂ and 1. Molecular docking analyses reveal that both LH₂ and 1 reside in domain-I of HSA.

Keywords: HSA binding; ITC; Molecular docking; Osazone; Palladium.