Chemical biology with organometallics

ORGN 67

Eric Meggers, meggers@sas.upenn.edu, Department of Chemistry, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104
Organometallic compounds often display unconventional structures, unusual reactivities, and exceptional catalytic activities. The presentation will illustrate how these properties can be applied to the design of molecules with novel biological properties. For example, recent results from our laboratory demonstrate that organometallic compounds can function as highly potent and selective enzyme inhibitors. In this respect, we like to think of a metal center as a hypervalent carbon with new opportunities to build shape and functional group diversity in an economical fashion. Following this strategy, a recipe is introduced for morphing indolocarbazole alkaloids into simple and easily accessible metal complexes, leading to the discovery of picomolar inhibitors for protein kinases. To go even a step further, in addition to molecular recognition, it is intriguing to imagine the design of bioactive small molecules with yet another function – that of catalysis. The ability to catalyze transformations in a biological environment by a small molecule could vastly expand our ability to influence biological processes at will, for example by releasing prodrugs in a spatially and temporally defined fashion. Our progress into this direction is demonstrated by the development of organometallic transformations which can be performed in biological environments such as living mammalian cells.