Many cytotoxic metal complexes interact with or damage DNA. While this provides for effective cell killing, the non-selective mechanism leads to potential off-target effects. A promising approach is to develop compounds capable of targeting and damaging key biological molecules, such as specific nucleic acid structures, sequences, or proteins. However, unless highly potent (nM activity) compounds are identified, the nature of non-covalent interactions between the compound and the biological target necessitates high concentrations, which once again, can lead to off-target effects. An alternative is to develop agents that can be induced to form covalent bonds to their targets using an external trigger, permanently damaging or inactivating essential biological molecules. A family of coordination complexes have been developed that can form covalent bonds only upon irradiation with visible to near-IR light. These compounds can be designed to target different nucleic acids or proteins within the cell, depending on the compounds’ structure and charge. The potential to develop agents that target various essential cellular processes will be explored.

Exploring the nucleic acid and protein interactions of cytotoxic ruthenium complexes

249th National Meeting (2015)

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