Bioorthogonal Chemistry
Reaction methodology in the service of biology.
We have a longstanding interest in developing chemical reactions that can be performed in living systems, i.e., cells, model organisms, and eventually, human patients. Termed “bioorthogonal chemistries”, these reactions enable chemical modification of complex biological molecules in their native environments, with applications that include molecular imaging, in situ drug assembly, enzyme activity probing and interrogation of noncovalent complexes in cells. We explore the reaction manifolds of functional groups that do not exist in nature and have no inherent reactivity with natural components. Quintessential examples are reactions of azides with triaryl phosphines and strained alkynes, transformations that we call the Staudinger ligation and “copper-free click chemistry”, respectively. These reactions have such high selectivity and efficiency that they can be performed in cells and organisms (i.e., C. elegans, zebrafish and mice). We aim to integrate such bioorthogonal reactivity into the design of smart probes for in vivo imaging, an effort that involves fundamental mechanistic and photophysical studies as well as innovative synthetic strategies. New bioorthogonal transformations are also under development, with a focus on exploiting or inventing functional groups that are orthogonal to current cohort.