Novel tetraaza macrocyclic Schiff base complexes of bivalent zinc: microwave-assisted green synthesis, spectroscopic characterization, density functional theory calculations, molecular docking studies, in vitro antimicrobial and anticancer activities

In the present manuscript, novel macrocyclic Schiff base complexes [Zn(N 4 MacL 1 )Cl 2 –Zn(N 4 MacL 3 )Cl 2 ] were synthesized by the reaction of ZnCl 2 and macrocyclic ligands (N 4 MacL 1 –N 4 MacL 3 ) derived from diketone and diamines under microwave irradiation method and conventional method. The structures of the obtained complexes were identified by various spectrometric methods such as Fourier transformation infra-red (FT-IR), nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), powder X-ray diffraction, molar conductivity, and UV–vis. The structures of the synthesized compounds were optimized by using the def2–TZV/J and def2–SVP/J Coulomb fitting basis sets at B3LYP level in density functional theory (DFT) calculations. The macrocyclic Schiff base complexes exhibited higher activities against Gram-positive bacteria ( Staphylococcus aureus and Bacillus cereus ), Gram-negative bacteria ( Escherichia coli and Xanthomonas campestris ), and fungal strains ( Fusarium oxysporum and Candida albicans ) in comparison to macrocyclic Schiff base ligands. Furthermore, the newly synthesized macrocyclic compounds were assessed for their anticancer activity against three cell lines: A549 (human alveolar adenocarcinoma epithelial cell line), HT-29 (human colorectal adenocarcinoma cell line), and MCF-7 (human breast adenocarcinoma cell line) using the MTT assay. The obtained results showed that the macrocyclic complex [Zn(N 4 MacL 3 )Cl 2 ] displayed the highest cytotoxic activity (2.23 ± 0.25 µM, 6.53 ± 0.28 µM, and 7.40 ± 0.45 µM for A549, HT-29, and MCF-7 cancer cell lines, respectively). Additionally, molecular docking investigations were conducted to elucidate potential molecular interactions between the synthesized macrocyclic compounds and target proteins. The results revealed a consistent agreement between the docking calculations and the experimental data. Graphical abstract