Synthesis and In-Silico Structural Analysis of Phenoxo-Bridged Zn(II) Complexes Targeting Spike Protein of SARS-CoV-2

The research article reports the optimized geometry of Se bearing 24- and 28-membered macrocyclic Schiff bases, LaH2, LbH2 and their reactions with zinc metal ion. The lowest energy optimized configuration of the Schiff bases adopts a bowl shape geometry with two benzoyl rings attached at carbon atom of C=N form the base of bowl and remaining two opening it. The reactions of these Schiff bases with ZnCl2 in methanol in 1:2 molar ratios under argon atmosphere resulting in the formation of bimetallic Zn(II) complexes having composition [Se{(CH2)2N=CPhC6H2(O)(4-CH3)PhC=O}2.Zn2Cl2], (1)  and [Se{(CH2)3N=CPhC6H2(O)(4-CH3)PhC=O}2.Zn2Cl2], (2). During the reaction, the proligands underwent partial hydrolytic cleavage at the C=N positions. In these complexes, the molecule of partially hydrolyzed proligands behaves like hexadentate (N2O4) ligands and binds with two Zn atoms via two of each azomethine nitrogen, benzoyl oxygen and the phenolic oxygen. The two Zn(II) ions are bridged through the phenolic oxygen atoms. Each Zn(II) is further bonded with a chloride ion which occupy the axial position in the geometries. Both of the Zn(II) complexes indicate the square pyramidal geometry; centered on the Zn atom which are connected by two edges that share oxygen atoms and are trans to each other. Furthermore, there are two basal planes in complexes 1 and 2; one around each Zn(87) and Zn(88) atoms. Both the basal planes of complex 1 are very slightly distorted at the zinc centers with a dihedral angle of about 1⁰; the basal planes of complex 2 are more distorted as compared to those of complex 1 with a dihedral angle of about 34⁰ at Zn(87) center while 14⁰ at other Zn site. The synthesized complex 1 exhibits a significantly stronger binding affinity to the spike protein of SARS-CoV-2 compared to commonly used drugs such as chloroquine, hydroxychloroquine, and remdesivir.