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C–H bond Hydroxylation at Non-Heme Carboxylate-Bridged Diiron Centers

Omar Villanueva, Cora MacBethEmory University

C–H bond Hydroxylation at Carboxylate-Bridged Diiron Centers

(1)Friedle, S. et al. Chem. Soc. Rev., 2010, 39, 2768-2779.(2)Kopp, D. A. et al. Curr. Opin. Chem. Biol., 2002, 6, 568-576.

In biology, a family of metalloproteins called bacterial multicomponent monooxygenases (BMMs) catalyze the hydroxylation of strong C–H bonds using dioxygen (O2) as the oxidant. Soluble methane monooxygenase (sMMO) is one of the most widely-studied protein in this family which converts methane (CH4) to methanol (CH3OH) using O2. The soluble hydroxylase component (sMMOH) is responsible for dioxygen activation and substrate hydroxylation. In particular MMOH contains a carboxylate-bridged non-heme diiron active site.1

Overview: General Reaction

Active site of sMMOH in its reduced state2

Mechanistic Overview

Overall changes in the diiron core upon activating dioxygen:

(1)Rosenzweig, A. C. et al. Nature, 1993, 366, 537.(2)Tshuva E. Y. et al. Chem. Rev., 2004, 104, 987-1012.

Detailed Mechanism:

Synthetic Models – Bioinspired Catalyst Design

(1) Du Bois, J. et al. Coord. Chem. Rev. 2000, 443, 200-202.(2) Jones, M. B. et al. Inorg. Chem. 2011, 50, 6402-6405.

Synthetic carboxylate-bridged diiron(II) complexes have been extensively studied as both structural and functional models of these active sites.1

Jones et al. report a diiron(II) complex (shown above) containing two bridging amidate ligands as a functional model of diiron(II) hydroxylase.2 These studies suggest bridging amidate ligands may be used in synthetic functional models of diiron enzymes that activate dioxygen and C-H bonds

Problems

Nature has evolved to allow diiron carboxylate-bridged systems such as in MMOH to selectively convert methane to methanol in methanotrophic bacteria.

1. Compare the active site of MMOH to those metalloenzymes that host a non-heme mononuclear iron center. What are the major differences in their motifs that dictate the differences in reactivity?

2. Modeling the chemistry of non-heme diiron proteins such as MMOH is very challenging. In functional synthetic models of MMOH, what are the key components that allow for similar catalytic reactivity such as in the protein?

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Contributed by: Omar Villanueva, Cora MacBeth

Emory University, 2014