Synthesis, structural characterization of phenoxo-bridged zinc(II) complexes and their binding interaction with the spike protein of SARS-CoV-2

Abstract

The research article reports the synthesis and structural study of the optimized geometry of selenium (Se) bearing 24- and 28- membered macrocyclic Schiff bases, L_aH₂, L_bH₂ and their reactions with zinc metal ion. The reactions of the macrocyclic Schiff bases with ZnCl₂ in 1:2 molar ratios result in the formation of bimetallic Zn(II) complexes having molecular composition [Se{(CH₂)₂N = CPh(4-CH₃-C₆H₂O) PhC = O}₂ · Zn₂Cl₂], (1) and [Se{(CH₂)₃N = CPh(4-CH₃-C₆H₂O)PhC = O}₂ · Zn₂Cl₂], (2). Moreover, as confirmed by various physico-chemical techniques such as elemental analysis, UV–Vis, FTIR,¹H NMR, and mass spectrometry, the proligands underwent partial hydrolytic cleavage at one of the C = N positions and behave like hexadentate (N₂O₄) ligands binding to two Zn(II) ions via bridging through the O_phenolic atoms, which results in a square pyramidal geometry around Zn(II) with the chlorine atom occupying axial positions. Further, following density functional study, the stable optimized configuration of the Schiff bases L_aH₂ and L_bH₂ is found to adopt bowl shape geometry. Conversely, in molecular docking studies, the synthesized complex 1 exhibits a significantly stronger binding affinity (−8.7 kcal/mol) to the spike protein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) as compared to the common coronavirus disease 2019 (COVID-19) treatment drugs such as chloroquine, hydroxychloroquine, and remdesivir with activity percentage showing more than 20% overall effectiveness than remdesivir and thus indicating its potential for COVID-19 therapeutics.

Graphical Abstract

Keywords:

• Se-containing Schiff bases
• Zn(II) complexes
• density functional theory
• molecular docking
• SARS-CoV-2 virus
• COVID-19

Disclosure statement

The authors have no conflict to disclose.

Acknowledgments

We are grateful to Prof. B. L. Khandelwal, DIMAT, Raipur for useful discussion, Dr. Sandeep Verma, IIT Kanpur for recording mass spectra, Prof. C. L. Khetrapal, CBMR, Lucknow for the NMR spectra, and Prof. S. K. Gupta for recording IR and UV–Vis spectra.

Conflict of interest statement

The authors of this manuscript do not have any conflict of interest.