Free Radical-Based Carbon Monoxide Release from Organic Molecules for Cancer Therapy

Carbon-monoxide-releasing molecules, or CORMs, are a powerful method for improving the body's immune response to certain cancers. Current approaches commonly utilise photoactive or transition metal-based complexes unsuitable for human applications. In this project, we propose an alternative approach that harnesses free radical-based decarbonylation of simple organic molecules for treating certain cancers. The cancer cell environment, rich in glutathione and reactive oxygen species, will allow the generation of reactive radicals capable of selectively abstracting hydrogen atoms from formyl groups. The radical formed will rapidly release a carbon monoxide (CO) molecule and a stabilised radical, which can in turn generate more thiyl radicals to propagate CO release. A combination therapy approach would utilise thioester-based prodrugs for release of both CO and, subsequently, an anticancer drug.