Metal-promoted synthetic chemistry within living cells

Bioorthogonal chemistry refers to the set of chemical reactions that can be used in vivo for the covalent modification of biomolecules and biopolymers. Most of these reactions rely on metal-free cycloadditions and on the use of tailored, strained reactants; therefore, their scope in terms of synthetic potential and versatility is limited. A crescent number of examples demonstrate that organometallic catalysts can also be implemented in biological environments, yet with modest efficiencies and mainly for uncaging/deprotection processes. Metal-promoted bioorthogonal transformations involving bond-forming, synthetic processes, are now starting to see the light. Considering the enormous breadth and versatility of organometallic catalysis in synthetic chemistry, this emerging field of synthetic bioorthogonal catalysis promises to have a profound impact on biology and biomedicine. The ability to perform 'new-to-nature' chemical reactions within living cells and organisms is transforming the way in which scientists interrogate and/or manipulate biological processes. In recent years, the toolbox of bioorthogonal and cell-compatible reactions has been enriched with the incorporation of transition metal-mediated processes. Whereas the efficiency of these reactions is still low, the breadth and generality of organometallic catalysis promises to significantly impact the field of bioorthogonal chemistry. Particularly attractive is the possibility of using organometallic catalysis for performing bond-forming, synthetically relevant reactions, as this could allow assembly of biorelevant products at specific biological sites. The ability to perform 'new-to-nature' chemical reactions within living cells and organisms is transforming the way in which scientists interrogate and/or manipulate biological processes. In recent years, the toolbox of bioorthogonal and cell-compatible reactions has been enriched with the incorporation of transition metal-mediated processes. Whereas the efficiency of these reactions is still low, the breadth and generality of organometallic catalysis promises to significantly impact the field of bioorthogonal chemistry. Particularly attractive is the possibility of using organometallic catalysis for performing bond-forming, synthetically relevant reactions, as this could allow assembly of biorelevant products at specific biological sites. emergent discipline of chemical biology that deals with the development of live-compatible bond-forming transformations for the synthesis of tailored products. copper-promoted cycloaddition between a terminal alkyne and azide to give 1,4-disubstituted-1,2,3-triazoles. biological polymers constituted by amino acids, responsible for catalyzing chemical reactions in living cells and organisms. Some of them contain metal cofactors at their active site and thus they are coined as metalloenzymes. (4+2) cycloaddition between 1,2,4,5-tetrazines and strained alkenes that exhibit impressive reaction rates. cycloaddition between strained cyclooctynes and azides to give 1,4-disubstituted-1,2,3-triazoles. elements with partially filled d-orbitals, exhibiting several oxidation states, and capable of forming coordination complexes that can work as catalysts.