DEVELOPMENT OF BIOORTHOGONAL CHEMISTRY USING COORDINATION-DRIVEN 3-COMPONENT ASSEMBLY REACTION SYSTEMS

Abstract

We have developed the coordination-driven 3-component assembly (C3A) as a facile strategy to efficiently synthesize large libraries of Ru(II)−arene Schiff-base (RAS) complexes. RAS complexes enable transfer hydrogenation (TFH) of azide-based fluorogenic probe leading to intracellular fluorescence turn-on. This strategy can be extended to selectively inhibit the growth of S. aureus by exploiting endogenous hydride source, formate, to activate an azide-caged prodrug. In addition, C3A is also applicable to assembling libraries of isoelectronic Rh(III) and Ir(III) complexes. By virtue of this, we have developed a novel uncaging strategy to activate a prodrug within bacterial cells via Rh-mediated TFH of caging moiety, 1,2-dithiane-4,5-diol, using native formate as the hydride source. Besides, RAS complexes efficiently catalyze thiol oxidation mimicking thiol oxidase as new bioorthogonal ligation chemistry. We envision this strategy may find its applications in chemical biology, bioengineering, and medicine.