关键词: 肉桂醛衍生物, 铜基金属配合物, 化学动力学治疗, 羟基自由基, 抗肿瘤

The development of structurally well-defined metal complexes with Fenton-like catalytic activity is of great significance for the multifunctional design and efficacy-toxicity optimization of chemodynamic therapy (CDT) agents. The complex crystallizes in triclinic space group P ī with a distorted tetrahedral geometry around each Cu(I). In this study, 4-methoxycinnamaldehyde and oxalyl dihydrazide were employed as starting materials to synthesize the 4-methoxycinnamaldehyde oxalyl dihydrazone ligand (MC-OD) via a condensation reaction. Subsequent coordination with triphenylphosphine and copper(II) nitrate afforded a dinuclear copper(I) complex (MC-OD-Cu). The molecular structure of the complex was unambiguously characterized by single-crystal X-ray diffraction, and its physicochemical stability as well as Fenton-like catalytic performance were systematically evaluated. XPS and Auger spectroscopy confirmed the Cu(I) valence state, while MB degradation and EPR experiments verified the generation of •OH. The EPR spectrum exhibited a typical 1:2:2:1 quartet signal, and the UV-vis absorbance of methylene blue at 655 nm decreased sharply after reaction. In vitro cellular assays demonstrated that the complex efficiently catalyzes the decomposition of intracellular hydrogen peroxide to generate substantial reactive oxygen species (ROS), thereby triggering oxidative stress damage in tumor cells and subsequently inducing apoptosis. The complex showed potent cytotoxicity against HeLa cells (IC₅₀ = 0.98 μmol/L) with moderate selectivity over normal cells. Specifically, the selectivity index was approximately 3-4, based on IC₅₀ values against normal cell lines such as HCV-29, HL-7702 and W138. Flow cytometry indicated concentration-dependent apoptosis induction, even at near-IC₅₀ concentrations. Notably, the complex exhibited significant antiproliferative activity against tumor cells. Collectively, MC-OD-Cu represents a promising class of novel chemodynamic antitumor agents. This study provides an experimental basis and theoretical basis for the application of cinnamaldehyde-derived metal complexes in tumor chemodynamic therapy. The single crystals of the complex were obtained by slow volatilization of a saturated mixed solvent of methanol and dichloromethane at room temperature after filtration and left undisturbed for several days.

Key words: cinnamaldehyde derivatives, copper-based metal complexes, chemodynamic therapy, hydroxyl radicals, antitumor