Carbon Monoxide-Releasing Molecules as a Dual-Warhead Approach to Antibiotics

Overview

Increasingly, certain bacteria are developing resistance to antibiotics and there is an urgent need to develop multi-functional drugs that will overcome the resistance of these 'super-bugs'. This project investigated the possibility of using carbon monoxide (CO), delivered in a safe and targeted way through special carrier molecules, as an antibacterial agent alongside conventional antibiotics.

A novel iron tricarbonyl scaffold based on the chalcone motif was prepared and fully characterized. In addition the factors affecting the CO-release mechanism for these complexes was investigated with a range of in situ spectroscopic techniques. Although the complexes did not inhibit the growth of Escherichia coli, the development of the new synthetic methods for the preparation of the compounds will significantly aid with the realisation of future generations of carbon monoxide-releasing molecules.

For example, the study has revealed the type of synthetic methods which have the greatest chance of success when attempting to incorporate additional functionality into the iron tricarbonyl scaffold. Such insights into synthetic methods will be crucial when selecting the best antibiotic structures for incorporation in dual-warhead carbon monoxide-releasing molecules.

Future studies will evaluate the compounds prepared in this study against other bacteria such as Pseudomonas aeruginosa and Staphylococcus aureus since related studies have shown that the activity of such compounds is strongly bacterium-dependent. Hence, there is still the potential for these iron carbonyls to be used successfully as antibiotics.