Bioactive benzoxazinone-based hydrazone metal complexes: synthesis, characterization, DFT analysis, and molecular docking studies

Abstract

The strategic design of novel ligands is essential in the synthesis of innovative metal complexes, as it allows for precise metal coordination that imparts distinctive structural frameworks, tailored physicochemical characteristics, and enhanced biological functionalities, thereby unlocking new possibilities for advanced technological and therapeutic applications. This work introduces the design and exploration of a hydazide-hydrazone based ligand 2-aminonicotinaldehyde benzoxazinonyl acetic acid hydrazone (ABAH) and its novel Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pd(II) complexes, which were comprehensively characterized using spectroscopic, physicochemical, and computational techniques. Spectral and DFT analyses support the coordination of ABAH acts as a neutral bidentate ligand through azomethine nitrogen and amide oxygen atoms. Based on the combined experimental and computational data, tentative octahedral geometries are proposed for the Co(II) and Ni(II) complexes, a distorted octahedral geometry is proposed for the Cu(II) complex, a tetrahedral geometries are proposed for the Zn(II) and Cd(II) complexes and a square-planar geometry for the Pd(II) complex. Molecular docking studies against HER2 and EGFR proteins revealed strong binding affinities, particularly for Ni(II) and Cu(II) complexes, corroborating their anticancer activities observed in vitro against multiple human cancer cell lines, with selective toxicity over normal HEK-293 cells. The Co(II) and Cd(II) complexes exhibited broad-spectrum antimicrobial efficacy surpassing standard drugs in some cases, while Ni(II) and Cu(II) complexes demonstrated strong antioxidant activity in the DPPH assay, although their activities were slightly lower than that of the reference standard ascorbic acid. Additionally, non-linear optical (NLO) properties derived from DFT calculations indicated enhanced hyperpolarizability in the metal complexes relative to the free ligand, suggesting potential applications in advanced optical materials. Overall, the results indicate that metal coordination substantially influences the structural, electronic, and biological properties of ABAH. The Ni(II) and Cu(II) complexes showed the most pronounced antioxidant and cytotoxic responses, while Co(II) complex exhibited notable antimicrobial activity. The combined experimental and computational findings provide a basis for further investigation of ABAH metal complexes as coordination-based bioactive systems, while additional structural, mechanistic, stability, and in vivo studies are required to establish their practical biomedical or materials applications.