Copper(II) Complexes of Hydrazone and Thiosemicarbazone Ligands: Synthesis, Characterization, Antibacterial and Antifungal Activity

Introduction

Biological activity of hydrazones and thiasemicarbazones is well-described: thiosemicarbazide moiety is present in the structure of thioacetazone, isoniazid-derived hydrazones demonstrate a high activity against Mycobacterium spp., whereas 5-nitrofuran-derived hydrazones prove effective in the treatment of urinary tract infections. Such compounds are also known to readily form Cu(II) complexes with a high antibacterial activity attributed to ROS generation and subsequent apoptotic cell death. Antifungal properties of thiosemicarbazone ligands and their Cu(II) complexes have been linked to alteration of ergosterol biosynthesis and membrane damage.

Methods

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, and elemental, XRD powder diffraction and thermogravimetric analysis studies.

Results

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.

Conclusions

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.