Synthesis, characterization and interaction studies of copper based drug with Human Serum Albumin (HSA): Spectroscopic and molecular docking investigations

A new water soluble copper(II) complex, [Cu(glygly)(ssz)(H2O)]⋅6H2O, 1 derived from dipeptide (glycyl glycine anion) and sulfasalazine was synthesized and characterized by elemental analysis (CHN), molar conductance measurements and spectroscopic methods (IR, UV–vis, ESI-MS). The complex 1 is non-ionic in nature and possess octahedral geometry around Cu(II) metal ion. The interaction of complex 1 with Human Serum Albumin (HSA) was investigated under physiological condition in Tris–HCl buffer solution at pH 7.4 by means of various spectroscopic methods (fluorescence, CD and FTIR) and molecular docking technique. The results of fluorescence titration revealed that the complex 1 strongly quench the intrinsic fluorescence of HSA through a static quenching procedure. Binding constants (Kb) and the number of binding sites (n ≈ 1) were calculated using modified Stern–Volmer equations. The thermodynamic parameters ΔG at different temperatures were calculated subsequently the value of ΔH and ΔS was also calculated which revealed that the hydrophobic and hydrogen bonding interactions play a major role in HSA–complex 1 association. The distance r between donor (HSA) and acceptor (complex 1) was obtained according to fluorescence resonance energy transfer and the alterations of HSA secondary structure induced by complex 1 were confirmed by FT-IR and CD measurements.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The interaction of complex 1 with HSA was investigated by spectroscopic and molecular docking techniques. ► The secondary structure of protein has been changed upon the interaction with complex 1. ► Complex 1 quenched the fluorescence of HSA through static quenching mechanism. ► Site I of the protein is found to be the main binding site for complex 1.