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

释放一氧化碳的分子，或CORM，是提高人体对某些癌症的免疫反应的有效方法。目前的方法通常利用不适合人类应用的光敏或过渡金属基络合物。在这个项目中，我们提出了一种替代方法，利用简单有机分子的自由基脱羰基来治疗某些癌症。癌细胞环境富含谷胱甘肽和活性氧，将允许产生能够选择性地从甲酰基中提取氢原子的活性自由基。所形成的自由基将快速释放一氧化碳（CO）分子和稳定的自由基，其可进而产生更多的硫基自由基以传播CO释放。联合治疗方法将利用基于硫酯的前药来释放CO和随后的抗癌药物。

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.