Events & Seminars > Event Details

Where:

4:00 pm
Room 304, Chemistry Building

Metalloporphyrins in Chemical and Biological Catalysis – From C-H Hydroxylation to Fluorination

Speaker:

Professor Jay Groves
Princeton University

Hosted by: Professor Brent Gunnoe

In this lecture I will discuss recent developments from our lab in the areas of synthetic, biomimetic metalloporphyrin catalysts and those of novel, heme-thiolate APO biocatalysts
with an active site similar to that of cytochrome P450. These extracellular enzymes are capable of catalyzing the monooxygenation of a variety of substrates using H2O2 as a
terminal oxidant. We have found that APO enzymes efficiently catalyze the H2O2-dependent hydroxylation of simple alkanes, even ethane. Drug molecules are efficiently converted into P450-like metabolites. The benzylic hydroxylation of ethyl benzoic acid proceeds with 100% conversion and 95% ee. The hydroxylation of cyclohexane mediated by APO with H2
18O2 resulted in complete incorporation of the oxygen label into the hydroxyl group of the product cyclohexanol. Hydroxylation of the radical clock norcarane led to a product mixture indicative of a radical rebound hydroxylation scenario with an estimated radical lifetime of ~10 ps. We have directly observed and kinetically characterized the reactive intermediate, « compound I », responsible for C-H hydroxylation.1-3 The mechanism of C-H hydroxylation by APO will be compared and contrasted to those of model porphyrin systems. We have recently described a selective and efficient C-H fluorination mediated by a model manganese porphyrin.4-7 Thus, C-H bonds that are chemically inaccessible by other means can be transformed to C-F bonds. The method allows the facile production of fluorinated drug analogs directly from the parent drug. Further, fluorination with 18F sources may allow access to new PET imaging agents.

 

1. Xiaoshi Wang, Sebastian Peter, Matthias Kinne, Martin Hofrichter, John T. Groves, Detection and
Kinetic Characterization of a Highly Reactive Heme–Thiolate Peroxygenase Compound I J. Am.
Chem. Soc., 2012, 134, 12897–12900.
2. John T. Groves, Enzymatic C-H Activation. Using Push to get Pull, Nature Chemistry, 2014, in press.
3. Xiaoshi Wang, Sebastian Peter, René Ullrich, Martin Hofrichter, and John T. Groves, Driving Force
for Oxygen-Atom Transfer by Heme-Thiolate Enzymes, Angew. Chem. Int. Ed. 2013, 52, 9238-9241.
4. Wei Liu, Xiongyi Huang, Mu-Jeng Cheng, Robert J. Nielsen, William A. Goddard, III, John T. Groves,
Oxidative Aliphatic C-H Fluorination with Fluoride Ion Catalyzed by a Manganese Porphyrin, Science,
2012, 337, 1322-1325.
5. Wei Liu and John T. Groves Mn-Catalyzed Oxidative Benzylic C-H Fluorination Using Fluoride Ion,
Angew. Chem. Int. Ed. 2013, 52, 6024-6027.
6. Wei Liu, Xiongyi Huang and John T. Groves, Oxidative aliphatic C-H fluorination with manganese
catalysts and fluoride ion, Nature Protocols, 2013, 8, 2348-2354.
7. Dong Wang and John T. Groves, Efficient water oxidation catalyzed by homogeneous cationic cobalt
porphyrins with critical roles for the buffer base, Proc. Nat. Acad. Sci. U.S.A., 2013, (39) 15579-15584.