Deciphering the effect of hydrophobicity on protein binding interaction in cobalt(II) complexes by multispectroscopic and computational methods

Abstract

In the present work, we report the synthesis, characterization of two cobalt complexes (1 and 2) and their HSA binding studies by multispectroscopic methods. Hirshfeld surfaces analysis and fingerprint plot analysis were carried out to identify intermolecular interactions viz., N–H···O, O–H···O and C–H···O linkages in crystal framework of the complexes. Density functional theory (DFT) studies were carried out to ascertain the electronic structure and molecular geometry of the complexes 1 and 2, and determine the localization of HOMO and LUMO in the complexes. A comparative in vitro interaction study of complex 1 and 2 with human serum albumin protein was carried out by employing UV-vis, fluorescence, circular dichroism, FTIR and molecular docking techniques. Interestingly, the HSA binding affinity of complex 2 was found to be more than complex 1 which was evidenced from the higher binding constant values owing to its strong hydrophobic topology. Further, a significant conformational change in microenvironment of HSA was noticed upon binding with complexes 1 and 2, nevertheless more perturbations were noticed in presence of complex 1. Molecular docking studies were carried out to validate the spectroscopic results and ascertain the preferential binding mode of complexes at the specific target site of HSA.

Communicated by Ramaswamy H. Sarma

Graphical abstract

Highlights

• The hydrophobicity of the two Co(II)-bipyridyl was modulated by changing their ligands

• The effect of change in hydrophobicity on their protein binding was investigated by multispectroscopic methods.

• Hirshfeld and DFT studies provided better insight about intermolecular interactions and electronic properties of complexes.

• The secondary structure of HSA was deeply perturbed upon interaction with the complexes

• Interestingly more pronounced effects were observed with complex 2 owing to its greater hydrophobic character.

Keywords:

• Co(II)-bipyridyl complexes
• DFT studies
• Hirshfeld surface analysis
• HSA interaction studies
• molecular docking studies

Acknowledgements

The authors also acknowledge the generous financial support from DST-PURSE program and DRS-1 (SAP) from UGC, New Delhi. The author (I. Yousuf) deeply acknowledges the financial support from University Grants Commission (UGC) New Delhi, for UGC Startup Grant (10057/B30531).

Disclosure statement

No potential conflict of interest was reported by the authors.