The fundamental importance of copper as a redox-active metal essential to the functioning of several metabolic enzymes provides a wide range of its biological activity pathways. Copper(II) coordination compounds are known to exhibit potent antiproliferative, antibacterial, nuclease, anti-inflammatory and antimycobacterial activities. Hydrazones are organic ligands commonly used for complexation with copper(II) that possess antibacterial, antiviral and antifungal properties. Copper–ligand interaction might facilitate charge delocalization and increase net hydrophobicity of the system, resulting in its enhanced pharmacological activity. Coordination compounds of Cu(II) with 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde derived hydrazone, nitrofurantoin and ftivazide have been synthesized, characterized by means of elemental and XRD analysis, FT-IR, UV-Vis and NMR spectroscopy and tested for antibacterial activity in vitro on Gram-positive and Gram-negative bacteria.

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.

Current research on synthetic and naturally occurring phenolic compounds is centered around their prominent antioxidant properties. Since reactive oxygen (ROS) and nitrogen (RNS) species cause considerable damage to cellular components upon their overproduction, associated with the pathogenesis of degenerative, cardiovascular and oncological diseases, antioxidants may reduce the risk of developing such conditions. Because hydroxyl, amino and sulfhydryl groups present in their structure, antioxidants may function as hydrogen atom and electron donors, as well as metal-reducing and metal-chelating agents. We synthesized phenolic Schiff bases from 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde; ortho-, meta- and para-mercaptoanilines; and 2,2′- and 4,4′-disulfanediyldianilines. Their antioxidant properties were studied in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay.

Nanoparticles are known to have a high specific surface area, which accounts for an increased probability of their interaction with bacterial cells. Therefore, the application of silver(I) nanoparticles (AgNPs) and their nanocomposites as antimicrobial agents against drug-resistant bacterial strains appears to be prospective. A critical point for the advancement of AgNPs into clinical practice is a fundamental understanding of their behavior in biological systems, including protein binding and interaction with blood components, which reflects their toxicity. The latter is primarily determined by the physicochemical properties of AgNPs, namely their size, shape, surface chemistry, etc. Therefore, nanotoxicity may be substantially reduced through the manipulation of certain physicochemical characteristics of AgNPs, increasing their biocompatibility and hence paving the way for possible biomedical applications. In this study we have focused on estimating the binding affinity of the synthesized Ag(I) complexes of 2-(4,6-di-tert-butyl-2,3-dihydroxyphenylsulfanyl)-acetic acid and 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde isonicotinoyl hydrazone, as well as AgNPs derived thereof to bovine serum albumin (BSA) and hemoglobin by the fluorimetric method. Furthermore, cellular toxicity of the AgNPs towards human erythrocytes was measured in a hemolysis assay. Organosols formed by the Ag(I) complexes upon their reduction to AgNPs in acetonitrile and DMSO were characterized by the transmission electron microscopy (TEM) method and atomic force microscopy (AFM).

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.