Structure–Spectroscopy Correlations for Intermediate Q of Soluble Methane Monooxygenase: Insights from QM/MM Calculations

Abstract

The determination of the diiron core intermediate structures involved in the catalytic cycle of soluble methane monooxygenase (sMMO), the enzyme that selectively catalyzes the conversion of methane to methanol, has been a subject of intense interest within the bioinorganic scientific community. Particularly, the specific geometry and electronic structure of the intermediate that precedes methane binding, known as intermediate Q (or MMOH Q ), has been debated for over 30 years. Some reported studies support a bis-μ-oxo-bridged Fe(IV) 2 O 2 closed-core conformation Fe(IV) 2 O 2 core, whereas others favor an open-core geometry, with a longer Fe–Fe distance. The lack of consensus calls for a thorough re-examination and reinterpretation of the spectroscopic data available on the MMOH Q intermediate. Herein, we report extensive simulations based on a hybrid quantum mechanics/molecular mechanics approach (QM/MM) approach that takes into account the complete enzyme to explore possible conformations for intermediates MMOH ox and MMOH Q of the sMMOH catalytic cycle. High-level quantum chemical approaches are used to correlate specific structural motifs with geometric parameters for comparison with crystallographic and EXAFS data, as well as with spectroscopic data from Mössbauer spectroscopy, Fe K-edge high-energy resolution X-ray absorption spectroscopy (HERFD XAS), and resonance Raman 16 O– 18 O difference spectroscopy. The results provide strong support for an open-core-type configuration in MMOH Q , with the most likely topology involving mono-oxo-bridged Fe ions and alternate terminal Fe-oxo and Fe-hydroxo groups that interact via intramolecular hydrogen bonding. The implications of an open-core intermediate Q on the reaction mechanism of sMMO are discussed.

A Combined Spectroscopic and Computational Study on the Mechanism of Iron-Catalyzed Aminofunctionalization of Olefins Using Hydroxylamine Derived N–O Reagent as the “Amino” Source and “Oxidant”

“…From the calculated Mössbauer spectrum of different conformers of Int II , the square-pyramidal isomer with the axial nitrogen SQP-N ax (δ = 0.47 mm/s, ΔE Q = 0.78 mm/s) gives a value relatively close to the experimental result (δ = 0.57 mm/s, ΔE Q = 0.40 mm/s) compared to the other models in terms of the isomer shift 140 , 143 − 146 ( Figure 7 b). A point to note is the quadrupole splitting is not considered for correlation as previous studies have shown that the predicted isomer shifts tend to be more reliable than the calculated quadrupole splittings.…”

“…The calculation of observables such as the spectroscopic and kinetic properties can serve as important guides in validating the results of calculations and identifying the nature of the observed intermediates. 140 Thus, correlation of the experimental results to the theoretical calculations are pursued in the subsequent section for electronic and structural elucidation of the reaction components (see Table S33 , SI for a comparative overview). We first apply this approach to the precursor complex 1 (see SI , computational section for details), to establish a benchmark for the correlations before extending this analysis to the geometric and electronic structures of the reaction intermediates ( Int I and Int II ), which are discussed in the next part of the manuscript.…”

“…A point to note is the quadrupole splitting is not considered for correlation as previous studies have shown that the predicted isomer shifts tend to be more reliable than the calculated quadrupole splittings. 140 , 144 , 146 − 148 In all the model conformers of Int II there is a decrease in calculated isomer shift value compared to Int I . The computed resonance Raman spectra for the most stable conformers of Int II (see computational section of SI ) agree well with the experimentally observed υs(Fe–O acac ) and υas(Fe–O acac ) stretches as well as the δ(H–N–Fe) bend with a small calculated 15 N isotope shift in agreement with the experimental result ( Figure S40 , Table S24 and Table S25 , SI).…”

Nuclear Resonance Vibrational Spectroscopic Definition of the Fe(IV)2 Intermediate Q in Methane Monooxygenase and Its Reactivity

“…For OC −OH/O models possessing an OH–Fe 2 –(μ-O)–Fe 1 O structure, the Fe 1 O bond weakens the Fe 1 –(μ-O) bond, resulting in a shorter Fe 2 –(μ-O) bond, localizing ν as (Fe–O–Fe) on the Fe 2 side. This facilitates ν­(Fe–OH) + ν as (Fe–O–Fe) coupling, resulting in a symmetric mode ν 2 which would agree with the 690 cm –1 experimental data (Figure , bottom row, red box), as anticipated in a recent computational study of Q . Isotope labeling with 18 O 2 must be incorporated into the μ-O bridge to correlate to the decay product T, as well as either into the OH - or O terminal ligands.…”

A mono-oxo-bridged binuclear iron(iii) complex with a Fe–O–Fe angle of 180.0° and its catalytic activity for hydrogen evolution

“…Researchers still pay considerable attention to binuclear oxo-bridged non-haem iron complexes (containing the Fe–O–Fe unit) due to their potential uses in biological processes, catalysts, magnetic materials, etc. 1–8 We can design an appropriate ligand to chelate metal centers in a special frame and control the electron withdrawal from the metal ion core, thereby modifying the intramolecular exchange interaction. 9,10 Binuclear oxo-bridged complexes mainly contain tribridged-, 11 dibridged- 12,13 and monobridged- 14 species.…”