No abstract

The transfer of OH• from metal-hydroxo species to carbon radicals (R•) to give hydroxylated products (ROH) is a fundamental process in metal-mediated heme and nonheme C-H bond oxidations. This step, often referred to as the hydroxyl "rebound" step, is typically very fast, making direct study of this process challenging if not impossible. In this report, we describe the reactions of the synthetic models M(OH)(ttppc) (M = Fe (1), Mn (3); ttppc = 5,10,4,6

The nonheme iron dioxygenase 2‐(trimethylammonio)‐ethylphosphonate dioxygenase (TmpA) is an enzyme involved in the regio‐ and chemoselective hydroxylation at the C1‐position of the substrate as part of the biosynthesis of glycine betaine in bacteria and carnitine in humans. To understand how the enzyme avoids breaking the weak C2−H bond in favor of C1‐hydroxylation, we set up a cluster model of 242 atoms representing the first and second coordination sphere of the metal center and substrate binding pocket, and investigated possible reaction mechanisms of substrate activation by an iron(IV)‐oxo species by density functional theory methods. In agreement with experimental product distributions, the calculations predict a favorable C1‐hydroxylation pathway. The calculations show that the selectivity is guided through electrostatic perturbations inside the protein from charged residues, external electric fields and electric dipole moments. In particular, charged residues influence and perturb the homolytic bond strength of the C1−H and C2−H bonds of the substrate, and strongly strengthens the C2−H bond in the substrate‐bound orientation.

An iron(III) methoxide complex reacts with para-substituted triarylmethyl radicals to give iron(II) and methoxyether products. Second-order rate constants for the radical derivatives were obtained. Hammett and Marcus plots suggest the radical transfer reactions proceed via a concerted process. Calculations support the concerted nature of these reactions involving a single transition state with no initial charge-transfer. These findings have implications for the radical "rebound" step invoked in nonheme iron oxygenases, halogenases, and related synthetic catalysts.

Decarboxylation of fatty acids is an important reaction in cell metabolism, but also has potential in biotechnology for the biosynthesis of hydrocarbons as biofuels. The recently discovered nonheme iron decarboxylase UndA is involved in the biosynthesis of 1‐undecene from dodecanoic acid and using X‐ray crystallography was assigned to be a mononuclear iron species. However, the work was contradicted by spectroscopic studies that suggested UndA to be more likely a dinuclear iron system. To resolve this controversy we decided to pursue a computational study on the reaction mechanism of fatty acid decarboxylation by UndA using iron(III)‐superoxo and diiron(IV)‐dioxo models. We tested several models with different protonation states of active site residues. Overall, however, the calculations imply that mononuclear iron(III)‐superoxo is a sluggish oxidant of hydrogen atom abstraction reactions in UndA and will not be able to activate fatty acid residues by decarboxylation at room temperature. By contrast, a diiron‐dioxo complex reacts with much lower hydrogen atom abstraction barriers and hence is a more likely oxidant in UndA.