Biological activity of hydrazones and thiasemicarbazones is well-described: thiosemicarbazide moiety is present in the structure of an antibacterial drug thioacetazone, hydrazone derivatives of isoniazid demonstrate a high activity against Mycobacterium spp., whereas 5-nitrofuran-2-carbaldehyde-derived hydrazones have proven effective in the treatment of urinary tract infections. Such compounds are also known to readily form Cu(II) complexes with a high antimicrobial activity attributed to ROS generation and subsequent caspase-dependent apoptotic cell death. Antifungal properties of thiosemicarbazone ligands and their Cu(II) complexes have been linked to alteration of ergosterol biosynthesis and membrane damage. 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde-derived hydrazones, thiosemicarbazones, and their Cu(II) complexes have been synthesized and characterized by NMR, ESR, FT-IR, UV-visible absorption spectroscopy, mass spectrometry, as well as elemental, XRD powder diffraction and thermogravimetric analysis studies. The obtained binuclear Cu(II) complexes have been found to possess the coordination polyhedron of [Cu₂L₂], HL being the formula of the corresponding ligand. Microbiological screening of the synthesized compounds against Gram-positive (Bacillus subtilis, Staphylococcus saprophyticus) and Gram-negative (Escherichia coli, Pseudomonas putida) bacteria has demonstrated a markedly enhanced antibacterial activity of hydrazone and thiosemicarbazone derivatives upon their complexation with the Cu(II) ion. Interestingly, antifungal activity of the 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde-derived hydrazones and thiosemicarbazones against Phytophthora spp. has been found to slightly decrease upon Cu(II) complexation. Due to tautomerism and metal chelation via anionic or neutral forms, biological activity of hydrazone and thiosemicarbazone derivatives can be controllably tuned by the formation of Cu(II) complexes of various coordination cores and nuclearities, rendering them promising basic structures for further modification.

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. Antifungal activity assays against Phytophthora infestans revealed that complexation with copper(II) affects the bioactivity of the hydrazone ligands differently depending on their structure: Cu(II) complexation reduced the activity of HL^I, whereas HL^II and its corresponding Cu(II) complex displayed comparable inhibitory activity.