Synthesis of Zn(ii) coordination complexes, their molecular design and docking with SARS-CoV-2 RBD protein and Omicron spike protein

Abstract

Two new Zn(II) coordination complexes, namely [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2), were synthesized and designed as self-assembled vaccine candidates against the SARS-CoV-2 receptor-binding domain (RBD) protein and Omicron spike protein (where L = (Z)-N-phenyl-N′-((Z)-phenyl(pyridin-2-yl)methylene)carbamohydrazonic acid, and en = ethylenediamine). Both the Zn(II) complexes were fully characterized using single-crystal X-ray crystallography, cyclic voltammetry, FT-IR spectroscopy, FT-Raman spectroscopy, NMR spectroscopy, UV-Vis and fluorescence spectroscopic experimental techniques and density functional theory calculations. Both the complexes were crystallized in the monoclinic crystal system with the P2₁/n space group. Crystallographic studies indicated a square pyramidal geometry for [Zn(L)(en)]ClO₄ (1) and distorted octahedral for [Zn(L)₂] (2). DFT calculations were performed to provide information on the structure–activity relationships. Hirshfeld surface (HS) analysis was also performed. The interactions of the Zn(II) complexes [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2) with CT-DNA were followed by UV-Vis studies. Absorption titration studies revealed that these interacted strongly with CT-DNA. The calculated equilibrium binding constant (K_b) values found were to be 4.75 × 10⁴ and 5.82 × 10⁴ L mol⁻¹ for [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2), respectively. The in vitro cytotoxicity and antibacterial potential of [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2) were studied. In order to gain an insight into the potential applications of the Zn(II) complexes as effective antivirus agents, we performed molecular docking of [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2) with the SARS-CoV-2 (PDB ID: 7LM9) receptor-binding domain (RBD) protein and the Omicron spike protein (PDB ID: 7WOP). The Zn(II) complexes demonstrated similar antivirus effects as ivermectin and levosalbutamol. Therefore, we also docked the control ivermectin (IVM) and levosalbutamol (LVM) with both the SARS-CoV-2 RBD protein (PDB ID: 7LM9) and the Omicron spike (S) protein (PDB ID: 7WOP). The synthesized Zn(II) complexes showed good docking results with the SARS-CoV-2 RBD protein and the Omicron spike (S) protein, suggesting they have the potential as drugs for use against SARS-CoV-2 and its Omicron variants. Molecular docking calculations of [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2) with DNA binding protein (PDB ID: 7UV7) showed that these interact with DNA via a groove binding mode. Overall, our molecular docking results showed that the synthesized Zn(II) complexes [Zn(L)(en)]ClO₄ (1) and [Zn(L)₂] (2) could be adopted as potential inhibitors for the development of new anti-SARS-CoV-2 Omicron drugs.