Book of Abstracts - Ruhr-Universität Bochum

P-66
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Synthetic Analogs for Evaluating Organometallic and Nickel(0) Involvement in
Acetyl Coenzyme A Synthase
Molly J. O’Hagan, Nathan A. Eckert, and Charles G. Riordan *a
a University of Delaware, Department of Chemistry and Biochemistry, 19716, Newark, USA.
E-mail: riordan@udel.edu
Acetyl coenzyme A synthase (ACS) is a NiFeS protein found in archaea and anaerobic organisms that
can grow on CO2 as their sole carbon source. 1 Some of these, including methane, acetate and sulfateproducing
organisms are found in the intestinal tracts of higher mammals including humans. ACS
catalyzes the dis/assembly of a methylcorrinoid, CO and CoA to acetyl CoA. The mechanism of the
reaction undoubtedly involves bioorganometallic intermediates, although none have yet to be directly
identified. Using small molecule synthetic chemistry, we seek to establish chemical precedents for
relevant, elementary steps in ACS catalysis. 2 Central among these is the transalkylation of
methylcorrinoid to a reduced site of the ACS cluster. One proposal for this site is a zero-valent nickel
ion. 3 Studies detailed in this presentation establish the feasibility and mechanistic boundaries for alkyl
group transfer to nickel(0) and nickel(I) acceptors with emphasis on our recent results in deducing the
mechanism of a model in which SN2 transfer to nickel(0) is suggested. 4
References
1. S.W. Ragsdale, E. Pierce, Biochim. Biophys. Acta 2008, 1784, 1873-1898.
2. (a) R. Krishnan, J.K. Voo, C.G. Riordan, L. Zakharov, A.L. Rheingold, J. Am. Chem. Soc. 2003,
125, 4422-4423; (b) R. Krishnan, C.G. Riordan, J. Am. Chem. Soc. 2004, 126, 4484-4485.
3. P.A. Lindahl, J. Biol. Inorg. Chem. 2004, 9, 516-524.
4. N.A. Eckert, W.G. Dougherty, G.P.A. Yap, C.G. Riordan, J. Am. Chem. Soc. 2007, 129, 9286-
9287.
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