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

The research article reports the synthesis and structural study of the optimized geometry of selenium (Se) bearing 24- and 28- membered macrocyclic Schiff bases, LaH2, LbH2 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)(2)N = CPh(4-CH3-C6H2O) PhC = O}(2) center dot Zn2Cl2], (1) and [Se{(CH2)(3)N = CPh(4-CH3-C6H2O)PhC = O}(2) center dot Zn2Cl2], (2). Moreover, as confirmed by various physico-chemical techniques such as elemental analysis, UV-Vis, FTIR,H-1 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 LaH2 and LbH2 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. [GRAPHICS] .