| 1. |
- Li, Jilai, et al.
(författare)
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A Computational Comparison of Oxygen Atom Transfer Catalyzed by Dimethyl Sulfoxide Reductase with Mo and W
- 2015
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1099-0682 .- 1434-1948. ; :21, s. 3580-3589
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Tidskriftsartikel (refereegranskat)abstract
- A thorough computational study has been performed to investigate oxygen atom transfer (OAT) reactions catalyzed by dimethyl sulfoxide reductase (DMSOR) with a catalytic molybdenum or tungsten ion. Thirteen different density functional theory (DFT) methods have been employed to obtain structural parameters along the reaction pathway, and single-point energies were computed with local correlation coupled-cluster methods [LCCSD(T0)]. For both Mo and W, most DFT methods indicate that the enzyme follows a twostep mechanism with a stable intermediate in which a DMSO molecule coordinates to the metal ion in the +IV oxidation state, and this is also confirmed by the LCCSD(T0) energies. The W-substituted models have a 26-30 kJ/mol lower activation barrier for the OAT reaction, and the reaction is 6370 kJ/mol more exothermic than that with Mo. Different DFT methods give widely different activation and reaction energies, which roughly depend on the amount of exact exchange in the method; these differences are also reflected in the structures, especially for the rate-limiting transition state. Consequently, there is quite a large variation in energies and various energy corrections (thermal, solvation, dispersion, and relativistic; up to 39 kJ/mol) depending on which DFT method is used to obtain the geometries. Therefore, a mechanism predicted by a single method should be viewed with caution.
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| 2. |
- Li, Jilai, et al.
(författare)
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Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods.
- 2015
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 119:26, s. 8268-8284
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Tidskriftsartikel (refereegranskat)abstract
- We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular, the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerization reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site.
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| 3. |
- Li, Jilai, et al.
(författare)
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Comparison of the active-site design of molybdenum oxo-transfer enzymes by quantum mechanical calculations.
- 2014
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 53:22, s. 11913-11924
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Tidskriftsartikel (refereegranskat)abstract
- There are three families of mononuclear molybdenum enzymes that catalyze oxygen atom transfer (OAT) reactions, named after a typical example from each family, viz., dimethyl sulfoxide reductase (DMSOR), sulfite oxidase (SO), and xanthine oxidase (XO). These families differ in the construction of their active sites, with two molybdopterin groups in the DMSOR family, two oxy groups in the SO family, and a sulfido group in the XO family. We have employed density functional theory calculations on cluster models of the active sites to understand the selection of molybdenum ligands in the three enzyme families. Our calculations show that the DMSOR active site has a much stronger oxidative power than the other two sites, owing to the extra molybdopterin ligand. However, the active sites do not seem to have been constructed to make the OAT reaction as exergonic as possible, but instead to keep the reaction free energy close to zero (to avoid excessive loss of energy), thereby making the reoxidation (SO and XO) or rereduction of the active sites (DMSOR) after the OAT reaction facile. We also show that active-site models of the three enzyme families can all catalyze the reduction of DMSO and that the DMSOR model does not give the lowest activation barrier. Likewise, all three models can catalyze the oxidation of sulfite, provided that the Coulombic repulsion between the substrate and the enzyme model can be overcome, but for this harder reaction, the SO model gives the lowest activation barrier, although the differences are not large. However, only the XO model can catalyze the oxidation of xanthine, owing to its sulfido ligand.
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| 4. |
- Li, Jilai, et al.
(författare)
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Large Density-Functional and Basis-Set Effects for the DMSO Reductase Catalyzed Oxo-Transfer Reaction
- 2013
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 9:3, s. 1799-1807
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Tidskriftsartikel (refereegranskat)abstract
- The oxygen-atom transfer reaction catalyzed by the mononuclear molybdenum enzyme dimethyl sulfoxide reductase (DMSOR) has attracted considerable attention through both experimental and theoretical studies. We show here that this reaction is more sensitive to details of quantum mechanical calculations than what has previously been appreciated Basis sets of at least triple-zeta quality are needed to obtain qualitatively correct results. Dispersion has an appreciable effect on the reaction, in particular the binding of the substrate or the dissociation of the product (up to 34 kJ/mol). Polar and nonpolar solvation effects are also significant, especially if the enzyme can avoid cavitation effects by using a preformed active-site cavity. Relativistic effects are considerable (up to 22 kJ/mol), but they are reasonably well treated by a relativistic effective core potential. Various density-functional methods give widely different results for the activation and reaction energy (differences of over 100 kJ/mol), mainly reflecting the amount of exact exchange in the functional, owing to the oxidation of Mo from +IV to +VI. By calibration toward local CCSD (T0) calculations, we show that none of eight tested functionals (TPSS, BP86, BLYP, B97-D, TPSSH, B3LYP, PBEO, and BHLYP) give accurate energies for all states in the reaction. Instead, B3LYP gives the best activation barrier, whereas pure functionals give more accurate energies for the other states. Our best results indicate that the enzyme follows a two-step associative reaction mechanism with an overall activation enthalpy of 63 kJ/mol, which is in excellent agreement with the experimental results.
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| 5. |
- Ryde, Ulf, et al.
(författare)
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Computational Studies of Molybdenum and Tungsten Enzymes
- 2016. - 7
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Ingår i: Molybdenum and Tungsten Enzymes: Spectroscopic and Theoretical Investigations. - Cambridge : Royal Society of Chemistry. - 2045-547X. - 9781782628781 - 9781782628842 ; 2017-January:7, s. 275-321
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Bokkapitel (refereegranskat)abstract
- We review computational studies of three important mono-nuclear molybdenum oxo-transfer enzymes, dimethylsulfoxide reductase, sulfite oxidase and xanthine oxidase. We show that calculated energies for these reactions are very sensitive to details in the calculations, in particular to the density-functional method employed and the size of the basis set, but the treatment of dispersion and solvation effects is also crucial, as well as the definition of the reference state. We point out problems with standard quantum-mechanical (QM) cluster calculations, regarding the selection of the QM system and atomic coordinate constraints. Combined QM and molecular mechanics (QM/MM) methods also have important problems, which can be solved by calculations with very large QM systems (400-1000 atoms). Many studies have been published that reproduce experimentally measured activation energies, but for the wrong reason. We also compare the properties of molybdenum and tungsten and discuss why the active sites of the three families of molybdenum oxo-transfer enzymes are so different.
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| 6. |
- Sun, Xiaoli, et al.
(författare)
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Large Equatorial Ligand Effects on C-H Bond Activation by Nonheme Iron(IV)-oxo Complexes
- 2014
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Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 118:6, s. 1493-1500
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we present density functional theory (DFT) calculations on the iron(IV)-oxo catalyzed methane C-H activation reactions for complexes in which the Fe-IV=O core is surrounded by five negatively charged ligands. We found that it follows a hybrid pathway that mixes features of the classical sigma- and pi-pathways in quintet surfaces. These calculations show that the Fe-O-H arrangement in this hybrid pathway is bent in sharp contrast to the collinear character as observed for the classical quintet sigma-pathways before. The calculations have also shown that it is the equatorial ligands that play key roles in tuning the reactivity of Fe-IV=O complexes. The strong pi-donating equatorial ligands employed in the current study cause a weak pi(FeO) bond and thereby shift the electronic accepting orbitals (EAO) from the vertically orientated O p(z) orbital to the horizontally orientated O p(x). In addition, all the equatorial ligands are small in size and would therefore be expected have small steric effects upon substrate horizontal approaching. Therefore, for the small and strong g-donating equatorial ligands, the collinear Fe-O-H arrangement is not the best choice for the quintet reactivity. This study adds new element to iron(IV)-oxo catalyzed C-H bond activation reactions.
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| 7. |
- Van Severen, Marie-Céline, et al.
(författare)
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A quantum-mechanical study of the reaction mechanism of sulfite oxidase.
- 2014
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 19:7, s. 1165-1179
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Tidskriftsartikel (refereegranskat)abstract
- The oxidation of sulfite to sulfate by two different models of the active site of sulfite oxidase has been studied. Both protonated and deprotonated substrates were tested. Geometries were optimized with density functional theory (TPSS/def2-SV(P)) and energies were calculated either with hybrid functionals and large basis sets (B3LYP/def2-TZVPD) including corrections for dispersion, solvation, and entropy, or with coupled-cluster theory (LCCSD(T0)) extrapolated toward a complete basis set. Three suggested reaction mechanisms have been compared and the results show that the lowest barriers are obtained for a mechanism where the substrate attacks a Mo-bound oxo ligand, directly forming a Mo-bound sulfate complex, which then dissociates into the products. Such a mechanism is more favorable than mechanisms involving a Mo-sulfite complex with the substrate coordinating either by the S or O atom. The activation energy is dominated by the Coulomb repulsion between the Mo complex and the substrate, which both have a negative charge of -1 or -2.
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