Copper(II) Complexes of Hydrazones: Synthesis, Characterization and Activity Against Phytophthora infestans

Phytophthora spp. is recognized as one of the most widespread and destructive fungal pathogens of agricultural crops. Consequently, the discovery, development and rational application of chemical crop protection agents against this pathogen represent a matter of considerable urgency. In this context, hydrazones and their metal complexes, particularly those of copper(II), rank among the most promising candidates for antifungal screening. Owing to their straightforward synthesis, a wide range of substrates, and the ability to tailor structures with predefined physicochemical properties to diverse biological activities, copper(II) complexes of hydrazones are actively explored as antifungal agents. The biochemical mechanisms underlying the prominent antifungal properties of these compounds involve the overproduction of reactive oxygen species (ROS) and the induction of mitochondrial depolarization. A series of hydrazones derived from 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde (2-(4,6-di-tert-butyl-2,3-dihydroxybenzylidene)hydrazine-1-carboxamide and 4,6-di-tert-butyl-2,3-dihydroxybenzylidene-4-hydroxybenzohydrazide), along with their corresponding copper(II) complexes, have been synthesized and fully characterized by the methods of NMR, ESR, FT-IR and UV–visible absorption spectroscopy, complemented by elemental analysis, powder X-ray diffraction and electrochemical studies. The resulting binuclear copper(II) complexes were found to adopt a [Cu₂L₂] coordination motif (where L denotes the ligand). The synthesized compounds have demonstrated reducing properties, with the copper(II) complexes undergoing electrochemical oxidation more readily than the parent ligands, which could be the prerequisite for cellular redox cycling leading to ROS overproduction. Indeed, antifungal activity assays against Phytophthora infestans revealed that complexation with the copper(II) ion markedly enhances the bioactivity of the hydrazone ligands.