Synthesis, Spectral, Crystal structure, Hirshfeld surface, Computational analysis, and Antimicrobial studies of Ethyl-(E)-4-(2-(2arylidenehydrazinyl)-2-oxoethyl)piperazine-1-carboxylates

A new series of ethyl-(E)-4-(2-(2-arylidenehydrazinyl)-2-oxoethyl)piperazine-1-carboxylates (hydrazones) 4a-4e and 5a-5c were designed and synthesized from 1-ethoxycarbonylpiperazine. The hydrazones structure interpretations were achieved by spectroscopic analysis using FT-IR, 1D and 2D NMR and mass. Among the aforementioned hydrazones 4a-4e and 5a-5c, single crystal XRD structure was reported for hydrazone 4a. Both NMR and single crystal XRD analysis are clearly indicated the existence of E configuration of the azomethine group (-C=N-) and cis conformation of the amide group. Hirshfeld surface analysis and 2D fingerprint plot were employed to get a better understanding of non-covalent interactions (NCIs), which showed that the N-H center dot center dot center dot O and C-H center dot center dot center dot O intermolecular hydrogen bonding interactions are the key contributor to stabilize the molecular solids. Density functional theory (DFT) study was carried out to explore the geometrical parameters and electronic properties of frontiers molecular orbitals (FMO), global chemical reactivity descriptor parameter (GCRD), natural bond orbital (NBO), and non-linear optical (NLO) properties for 4a at B3LYP/6-311G(d,p) level. The molecular docking study was performed for hydrazone 4a with nCoV-SARS-2 main protease for COVID-19. Finally, the hydrazones in this synthetic series were screened for their antibacterial and antifungal activities using selected strains. Antimicrobial studies revealed that 4a and 5b against A. niger, 4c and 5c against K. pneumonia, 4e against B. subtilis, 5a, 5b, and 5c against A. flavus, A.niger and C. neoformans, respectively exhibits remarkable antibacterial and antifungal activity at a minimum concentration of 6.25 mu g/mL. (C) 2021 Elsevier B.V. All rights reserved.