Synthesis, molecular docking, molecular dynamic, quantum calculation, and antibacterial activity of new Schiff base-metal complexes

Abstract

The transition metals Co(II) and Cu(II) metal containing Schiff base-metal complexes are highly biological significance molecule for antimicrobial activity, as a result this study has been designed for investigation the synthesis, characterization, in vitro evaluation and in sillico study with molecular dynamic. To kick off, the new Schiff base free ligands, such as L1 and L2, were synthesized from the condensation of nicotinic acid carbohydrazide with vanillin or 2-chloroquinoline-3-carbaldehyde, respectively. The chemical structure of the synthesized Schiff base ligands, and their metal complexes have confirmed their structural geometry by spectroscopic analysis, such as 1H NMR, FTIR and UV-visible spectra, as well as confirming their chemical conversion (4-7) by metalation with the transition metals Co(II) and Cu(II). For evaluation the In vitro study, the antibacterial activity has screened against four human pathogenic bacteria. In addition, for developing the theoretical evaluation of the quantum calculation and biological activity, computational tools were used through the Density Functional Theory (DFT), molecular docking, molecular dynamics and ADMET study. It has revealed that the metal complexes (4-7) illustrate the higher antibacterial activity than the metal free ligands (1-2). The highest antibacterial activity conveys against P. vulgaris among E. coli, S. aureus and B. subtilis through disc diffusion method, and it is near to the standard (Gentamycin) for P. vulgaris. Next, the binding affinity of molecular docking study is more than −6.0 kcal/mol, while the L1-Co (4) shows the highest binding affinity among all bacterial pathogens. The molecular dynamics confirms their ligand-protein complex stability with high range of time (50 ns). Moreover, the Lipinski rule and ADMET properties were evaluated. Finally, the Cobalt complex {L1-Co (4)} shows the higher biological activity in views of both in vitro and computational study.