Synthesis, spectroscopic characterization, in vitro antimicrobial activity, antioxidant study and theoretical approaches towards DNA gyrase, DHFR enzyme, NADPH enzyme of N8-tetraoxomacrocyclic complexes of Zn(II)

Abstract

In the present work, novel N8-tetraoxomacrocyclic complexes of Zn(II) were synthesized from macrocyclic ligands (N8O4L1- N8O4L3) in a 1:1 zinc chloride to macrocyclic ligand ratio in methanol solvent. The structure of the newly synthesized compounds was confirmed by elemental analysis, infra-red (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS), UV–visible spectroscopy, and powder X-ray diffraction (XRD) studies. The spectral data indicated that macrocyclic ligands (N8O4L1- N8O4L3) functioned as tetradentate ligands, which coordinated to Zn(II) ions through the nitrogen atom of imine (>CN) group. Two chloro groups are covalently bound to Zn(II) ions, which are responsible for an octahedral environment around the zinc in macrocyclic complexes. Density functional theory (DFT) calculations were performed to support the resulting proposed octahedral structure and also to calculate the quantum chemical parameters. Subsequently, the macrocyclic compounds were examined against a panel of pathogenic microbes including Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungal strains (Aspergillus niger and Candida albicans) for their in vitro antimicrobial potential. The result showed that the macrocyclic complexes have remarkable antimicrobial potential as compared to their corresponding macrocyclic ligands at the same concentration. Then, the synthesized compounds were evaluated for their ability to scavenge free radicals using DPPH assay. The result showed that the macrocyclic complex [Zn(N8O4L3)Cl2] exhibited higher antioxidant efficacy among all the tested macrocyclic compounds with IC50 value 0.22 ± 0.025 mg/mL, relative to ascorbic acid (IC50 value = 0.12±0.01 mg/mL). Furthermore, molecular docking studies were performed to predict the exact binding mode of the newly synthesized compounds to the specified target proteins DNA gyrase (PDB ID 4DHU), DHFR enzymes (PDB ID 4HOF), and NADPH enzyme (PDB ID 2CDU). From the molecular docking studies, it was observed that the molecular docking results are in good agreement with the in vitro biological studies. Hence, it is concluded that macrocyclic ligands and their Zn(II) complexes have the potential to be explored as active antimicrobial and antioxidant agents.