Design, synthesis, reactivity, and biological activity of nitroimidazole derivatives and their copper(II) coordination compounds

In the last 60 years, the broad spectrum of activity of nitroimidazole derivatives against anaerobic bacteria, parasites, and protozoa has permitted their use as the first choice of treatment for many infectious diseases. New compounds are needed to overcome the acquired resistance of bacteria and parasites. This work aimed to investigate 4- and 5-nitroimidazole derivatives in terms of the contribution of the position of the nitro group, along with that of different substituents, on their chemical, structural, and biological properties. Copper (II) coordination compounds with these derivatives were synthesized and characterized by analytical and spectroscopical techniques. Their structural properties and their intra- and intermolecular interactions were analyzed from single crystal X-ray diffraction studies. Theoretical calculations allowed for explaining the lability in solution of the copper (II) coordination compounds with the 4-nitroimidazole derivatives. The potential antimicrobial activity against anaerobic periodontal and opportunistic aerobic bacteria, including E. coli , S. aureus , S. mutans , and P. gingivalis , was evaluated. It is noteworthy that the position of the nitro group in the heterocycle drives their coordination behavior toward the metal ions, the geometry of the copper (II) atom in the complexes, and their stability in solution, thus affecting their biological activity.