"This proposal aims at the discovery of robust transition-metal catalyzed transformations that can take place in aqueous media and cellular lysates, and are susceptible of being exported to living cells. Specifically, we will exploit the special coordination and activation ability of different metal complexes towards pi-systems to induce chemo-selective reactions of designed, abiotic, unsaturated substrates. Moreover, and importantly, the metal catalysts will be conjugated to designed ligands or biopolymers so that the catalytic power of the metal complex can be transferred to specific “in vivo” locations. Initial designs in this latter “high risk” endeavor will be guided by the current knowledge on metal-catalyzed bio-orthogonal chemistry as well as by some precedents on catalysis-based metal-sensing tactics.Ultimately, we want to install catalytic power in specific cellular sites and/or endow catalytic properties to any selected bio-molecular target. The catalytic activity could then be used to trigger the amplified generation of fluorescent signals or boost the production of bioactive drugs from inert, non-toxic precursors. This will set the basis for the development of efficient bio-sensing and imaging tools, and “in cellulo” diagnosis tactics, and of novel target-directed therapeutic strategies. With the crescent identification of disease-related biomarkers, the development of biomarker-associated diagnosis and therapy protocols is becoming one of the more urgent challenges in modern life sciences. Advances in early diagnosis can have a profound impact in public health, and boost new technology developments.The transversal expertise of my group in synthesis, metal catalysis, molecular recognition and chemical biology (see PI profile) places us in a rather unique position to tackle this type of interdisciplinary project."