Copper(ii) chelates of a coumarin-based acyl hydrazone ligand: structural characterization and computational evaluations for prospective applications in antimicrobial, antiviral, antioxidant, and anticancer therapies†

This study represents the synthesis and comprehensive characterization of four novel copper(II) chelates (CuR, CuRCT, CuH, and CuHCT) derived from a newly developed coumarin-based acyl hydrazone ligand (HCBH). The chelates were prepared using multidisciplinary synthetic routes, including reflux and hydrothermal methods with or without surfactant assistance, resulting in distinct mono- and binuclear structures with nanoscale morphologies. Structural analyses confirmed that all copper complexes possess tetrahedral geometries, with ligand coordination modes varying between tridentate and tetradentate depending on the synthetic method. TEM imaging revealed unique morphologies for each chelate, and the successful dispersion of the bioactive CuH chelate into silica yielded a porous nanostructured drug delivery system. Biological evaluations revealed promising antimicrobial activity, particularly for CuHCT against E. coli and S. aureus, and for CuRCT against B. subtilis and C. albicans. Antioxidant assays showed that CuRCT and CuHCT exhibited superior activity compared to other complexes and standard ascorbic acid. CuH demonstrated potent cytotoxicity against HepG-2 and MCF-7 cancer cell lines, comparable to cisplatin, while maintaining moderate toxicity toward normal Vero cells (CC₅₀ = 43.34 ± 1.98 μg ml⁻¹). Although the antiviral activity of CuH against HAV was weak, in vitro release studies of CuH–silica composites confirmed controlled release behavior, supporting its potential as a nanodrug delivery system. Density Functional Theory (DFT) and molecular docking analyses corroborated the biological findings, with favorable interactions observed between the compounds and CDK2 kinase. Collectively, these results highlight CuH as a highly promising candidate for further preclinical evaluation, especially in cancer therapy, with silica-based dispersion enhancing its potential as a nanocarrier for targeted drug delivery.