Cancer is one of the leading causes of death, and though numerous cancer treatments have been developed, the overall selectivity and effectiveness of treatments need to be improved. Exploiting differences between cancerous tissue and normal tissue has proven successful, and compared to normal tissue, cancerous tissue exhibits uncontrolled growth leading to inefficient blood vessel formation, restricting blood flow and the delivery of drugs and oxygen to the inner regions of tumors. The lack of oxygen, termed hypoxia, results in a reducing environment in tumors. Exploiting the reducing environment of tumors to activate a drug molecule offers a potentially selective treatment strategy. We aim to design pro-drugs that are initially administered to the body in an inactive form, and can be only selectively activated under the reducing conditions found in tumors. We synthesized octahedral CoIII complexes in which the metal center is coordinated by a tetradentate salen ligand and two axial imidazole ligands. We envision that upon reduction of the CoIII metal center to CoII, the axial ligands will be released from the more kinetically-labile metal centre. Salen ligand modification provides a mechanism to tune the compounds for selective release in the reducing environment of tumors. Our initial efforts involve the synthesis of a series of octahedral CoIII salen complexes incorporating monodentate fluorescent ligands in axial positions. The fluorescence is quenched while bound to the CoIII center, but upon release we can use fluorescence spectroscopy as a proof-of-principle for our design strategy. Our eventual goal is to use the CoIII complexes as a drug delivery platform for the selective release of axially-bound anticancer agents.

Cobalt (III) Complexes as Pro-drugs for Cancer Therapy

251st National Meeting (2016)

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