Metallodrugs represent an emerging and growing class of diagnostic and therapeutic pharmaceuticals. In analogy with organic drugs, the synthesis of metallodrugs that are released/activated slowly in the bloodstream and high molar activity (radio)pharmaceuticals remain key challenges. To this end, our lab has recently developed metal-complex mediated, autolytic amide bond cleavage (MMAC), a process that enables the selective cleavage of complex-adjacent amide bonds for release of drug cargo, pharmacokinetic modulators, or solid support. This presentation will discuss design, synthesis, assessment, and optimization of MMAC to occur under radiochemical and biologically relevant thermal and solvent conditions.

Metal-mediated, autolytic amide bond cleavage: An emerging strategy to synthesize and activate metallodrugs

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