Does Hydrogen‐Bonding Donation to Manganese(IV)–Oxo and Iron(IV)–Oxo Oxidants Affect the Oxygen‐Atom Transfer Ability? A Computational Study

Abstract

Iron(IV)-oxo intermediates are involved in oxidations catalyzed by heme and nonheme iron enzymes, including the cytochromes P450. At the distal site of the heme in P450 Compound I (Fe(IV) -oxo bound to porphyrin radical), the oxo group is involved in several hydrogen-bonding interactions with the protein, but their role in catalysis is currently unknown. In this work, we investigate the effects of hydrogen bonding on the reactivity of high-valent metal-oxo moiety in a nonheme iron biomimetic model complex with trigonal bipyramidal symmetry that has three hydrogen-bond donors directed toward a metal(IV)-oxo group. We show these interactions lower the oxidative power of the oxidant in reactions with dehydroanthracene and cyclohexadiene dramatically as they decrease the strength of the OH bond (BDEOH ) in the resulting metal(III)-hydroxo complex. Furthermore, the distal hydrogen-bonding effects cause stereochemical repulsions with the approaching substrate and force a sideways attack rather than a more favorable attack from the top. The calculations, therefore, give important new insights into distal hydrogen bonding, and show that in biomimetic, and, by extension, enzymatic systems, the hydrogen bond may be important for proton-relay mechanisms involved in the formation of the metal-oxo intermediates, but the enzyme pays the price for this by reduced hydrogen atom abstraction ability of the intermediate. Indeed, in nonheme iron enzymes, where no proton relay takes place, there generally is no donating hydrogen bond to the iron(IV)-oxo moiety.

Mechanistic insights into the catalytic reaction of plant allene oxide synthase (pAOS) via QM and QM/MM calculations

“…The TS3 is 15.4 kcal/mol, showing that the additional water molecule in-fact destabilizes TS3 unlike reports elsewhere [59,60]. This result agrees with the study of de Visser et al in which hydrogen bonding interactions reduce the catalytic activity in Fe(IV)-oxo biomimetic complexes [61]. In addition, additional water molecules were predicted to increase the activation barrier of the PCET between close Tyr radical and Cys residues in the different peptide chains in protein molecules by model DFT calculations [41].…”

Dichotomous Hydrogen Atom Transfer vs Proton-Coupled Electron Transfer During Activation of X–H Bonds (X = C, N, O) by Nonheme Iron–Oxo Complexes of Variable Basicity

“…As shown in Figure 5a, EER is observed for 4 but not for the more basic complexes 1 and 2 , which have much larger barriers. It is also worthy to note that the H-abstraction barriers of these basic oxidants with S1 are higher even than that of the analogous high spin [Fe IV OTMG 3 tren] 2+ oxidant (15.6 kcal/mol) 45 or of other Fe IV O complexes 5j,19 (Tables S20 and S21). The root cause of the higher HAT barriers for 1 and 2 is the significant basicity of these iron(IV)-oxo complexes.…”

How the Proximal Pocket May Influence the Enantiospecificities of Chloroperoxidase-Catalyzed Epoxidations of Olefins

“…Theoretical simulations of proximal pocket/sulfur hydrogen bonding in nitric oxide synthase showed that such bonding may affect the distribution of the thiolate/porphyrin unpaired spin [42]. The effect of hydrogen bonding to the distal oxygen of model manganese(IV)-oxo and iron(IV)-oxo oxidants on the oxidants’ ability for oxygen atom transfer was studied [43]. However, to the best of our knowledge, there are no published theoretical results regarding the possibility that the proximal helix and the NH–S bonds may affect the enantiospecificity of oxidations catalyzed by heme-thiolate enzymes.…”