Theory of chemical bonds in metalloenzymes. XIV. Correspondence between magnetic coupling mode and radical coupling mechanism in hydroxylations with methane monooxygenase and related species

Abstract

Broken-symmetry (BS) and approximate spin-projected (AP) BS hybrid density functional theory (DFT) calculations were performed to elucidate possible mechanisms of hydroxylation reactions of methane and alkanes with soluble methane monooxygenase (sMMO) and related metalloenzymes. The BS HDFT (UB3LYP) method was employed to elucidate electronic and spin structures of the key intermediate ''Q'' and to locate transition structures for hydroxylation reactions in the lowest-spin (LS) singlet and the highest-spin (HS) states of sMMO. The spin density populations and chemical indices obtained by the BS B3LYP calculations were found to be consistent with orbital interaction models for hydroxylation with MMO. However these indices in turn indicated significant spin contamination errors in the BS LS solution. The elimination of the errors with the AP procedure indeed reduced the barrier height for the recombination step of alkyl and hydroxyl radicals in the pure LS singlet state, leading to a rebound process. Then present computational results indicated that hydroxylation reactions proceed through the continuous diradical (diradicaloid) mechanism without discreet free radical fragments in the pure LS singlet state. The computational results are, respectively, compatible with local singlet (SD) and local triplet (TD) diradical mechanisms for hydroxylation in the LS and HS states; those were already applied to P450 successfully. Thus magnetic (exchange) coupling modes (LS and HS) in MMO, P450 and related metalloenzymes are directly related to local SD and TD mechanisms for hydroxylation, indicating the correspondence between the magnetic coupling mode and the radical reaction mechanism. These theoretical results enable us to examine recent BS hybrid DFT computational results for hydroxylation reactions with sMMO by several groups. Implications of the present theoretical and computational results are also discussed in relation to several experimental aspects of hydroxylation reactions.

Quantum Chemical Studies on Dioxygen Activation and Methane Hydroxylation by Diiron and Dicopper Species as well as Related Metal–Oxo Species

“…Although there is no significant difference between the structures in the HS-FM and HS-AF states, the structure in the IS state is different from that in the HS state in the coordination mode of Glu114. The Fe£Fe distances in the HS-FM, HS-AF, and IS-AF states are 2.70, 2.69, and 2.68 ¡, respectively, longer than those of the EXAFS study 32 by about 0.2 ¡, but close to the distance in the synthetic complex and those calculated by our group, 218 Siegbahn, 146 and Yamaguchi et al 219 In all the studied spin states, two of the FeO distances in the diamond core are short, and the other two are long, in good agreement with the EXAFS measurements. 32 The free energy gap between the HS-FM and HS-AF states for Model 1H is small, 0.4 (0.9 and 2.7) kcal mol ¹1 at the B3LYP (B3LYP* and OPBE) level.…”

Theory of chemical bonds in metalloenzymes. XVII. Symmetry breaking in manganese cluster structures and chameleonic mechanisms for the OO bond formation of water splitting reaction

“…The carbonyl groups of Asp189 and one water molecule are coordinated to Ca(II) ion in Va, while two water molecules are coordinated to Ca(II) ion in VIa. VIa can also be reduced to the Berlin (Loll) structure (IVa) [29] and to the London structure (IIIa) [27] by removing the O 4 and O 5 atoms, respectively.…”

“…In fact, the broken-symmetry density functional theory (BS DFT) calculations followed by the natural orbital analysis have elucidated that the OAO bond formation processes are qualitatively described by the superposition of these extreme VB configurations as U BS-Cl ¼ C 1 w 1 (DR) þ C 2 w 2 (ZW), where C i means a linear combination coefficient of the BS configuration responsible for the extreme diradical (DR) or zwitterion (ZW) electronic structure. As shown in the previous papers [3,4], the weight of DR or ZW is highly dependent on environmental conditions such as hydrogen bonding. The DR character of the Mn¼ ¼O bond can be variable as illustrated in Scheme S1A, Supporting Information, showing that the environmental conditions heavily affect the reactivity.…”

“…Thus, symmetry and broken symmetry play an important role for characterization of cluster structures of multinuclear iron-sulfur complexes in chemistry and biology. These are closely related to homolytic and heterolytic bond cleavages (or formations) in chemical reaction as discussed previously [3,4,[22][23][24][25]26]. SCHEME 1.…”

“…In this series of papers, we have elucidated correspondence between magnetic-coupling mode and reaction mechanism of several oxygenation reactions [3]. As shown in part XIV of this series [4], binuclear iron di-l-oxo complex, so-called intermediate Q, in soluble methane monooxygenase [5][6][7][8][9][10] exhibits antiferromagnetic and ferromagnetic exchange couplings. The antiferromagnetic and ferromagnetic states corresponds, respectively, to the local singlet and triplet diradical mechanisms for the monooxygenation reaction of methane as illustrated in Eq.…”