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N-O Bond Cleavage Mechanism(s) in Nitrous Oxide Reductase

Ertem, M. Z.; Cramer, C. J.; Himo, F.; Siegbahn, P. E. M.
J. Biol. Inorg. Chem. 2012, 17, 687 (doi:10.1007/s00775-012-0888-x).

Quantum chemical calculations of active site models of nitrous oxide reductase (N2OR) are undertaken in order to elucidate the mechanism of N-O bond cleavage mediated by the supported tetranuclear Cu4S core (CuZ) found in the enzymatic active site. Using either a minimal model previously employed by Solomon and co-workers (J. Am. Chem. Soc. 2006, 128, 278) or a more extended model including key residue side chains in the active-site second shell, two distinct mechanisms are found. In the first, already described by Solomon and co-workers, N2O binds to the fully reduced CuZ in a bent μ-(1,3)-O,N bridging fashion between the CuI and CuIV centers and subsequently extrudes N2 while generating the corresponding bridged μ-oxo species. In the second, substrate N2O binds loosely to one of the coppers of CuZ in a terminal fashion, i.e., using only the O atom; loss of N2 generates the same μ-oxo copper core. The free energies of activation predicted for these two alternative pathways are sufficiently close to one another that theory does not provide decisive support for either one over the other, posing an interesting problem with respect to experiments that might be designed to distinguish between the two. Effects of nearby residues and active-site water molecules are also explored.