| 1. |
|
|
| 2. |
- Ritacca, Alessandra G., et al.
(författare)
-
Unraveling the Reaction Mechanism of Mo/Cu CO Dehydrogenase Using QM/MM Calculations
- 2022
-
Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 12:12, s. 7336-7343
-
Tidskriftsartikel (refereegranskat)abstract
- Some microorganisms, like the aerobic soil bacteria, Oligotropha carboxidovorans, have the capability to oxidize the highly toxic atmospheric gas carbon monoxide (CO) into CO2 through CO dehydrogenase enzymes, whose active site contains a bimetallic MoCu center. Over the last decades, a number of experimental and theoretical investigations were devoted to understanding the mechanism of CO oxidation and, in particular, the role of a very stable thiocarbonate intermediate that may be formed during the catalytic cycle. The occurrence of such an intermediate was reported to make the CO2 release step kinetically difficult. In this work, by using an accurate QM/MM approach and energy refinement by means of the BigQM method, we were able to determine the role of such an intermediate and propose a novel mechanism for the oxidation of CO into CO2 by Mo/Cu CO dehydrogenase. Surprisingly, we found that the detachment of CO2 occurs directly from the product of the Mo=O nucleophilic attack reaction on the carbon of CO aided by the transient coordination of the active site glutamate to the Mo ion. The estimated activation barrier is in good agreement with the experimental one, while the thiocarbonate turned out to not interfere with the CO-oxidation catalytic cycle. The results highlight the importance of the environmental effects in the assembly of the molecular model and in the choice of the computational protocol. Our accurate modeling of the enzyme also allowed us to exclude the involvement of a frustrated Lewis pair in the CO-oxidation mechanism, which has recently been suggested based on an analysis of structural and electronic features of synthetic mimics of the Mo/Cu CO dehydrogenase active site.
|
|
| 3. |
- Rovaletti, Anna, et al.
(författare)
-
A thiocarbonate sink on the enzymatic energy landscape of aerobic CO oxidation? Answers from DFT and QM/MM models of Mo–Cu CO-dehydrogenases
- 2019
-
Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517. ; , s. 201-205
-
Tidskriftsartikel (refereegranskat)abstract
- We present a theoretical investigation providing key insights on a long-standing controversial issue that dominated the debate on carbon monoxide oxidation by Mo–Cu CO-dehydrogenases. Previous investigations gravitate around the possible occurrence of a thiocarbonate intermediate, that was repeatedly reported to behave as a thermodynamic sink on the catalytic energy landscape. By using a hierarchy of quantum mechanical and hybrid quantum/classical models of the enzyme, we show that no such energy sink is present on the catalytic energy profile. Consequent perspectives for the definition of a novel mechanistic proposal for the enzyme-catalyzed CO-oxidation are discussed in light of the recent literature.
|
|
| 4. |
- Rovaletti, Anna, et al.
(författare)
-
Can Water Act as a Nucleophile in CO Oxidation Catalysed by Mo/Cu CO-Dehydrogenase? Answers from Theory
- 2022
-
Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 23:8
-
Tidskriftsartikel (refereegranskat)abstract
- The aerobic CO dehydrogenase from Oligotropha carboxidovorans is an environmentally crucial bacterial enzyme for maintenance of subtoxic concentration of CO in the lower atmosphere, as it allows for the oxidation of CO to CO2 which takes place at its Mo−Cu heterobimetallic active site. Despite extensive experimental and theoretical efforts, significant uncertainties still concern the reaction mechanism for the CO oxidation. In this work, we used the hybrid quantum mechanical/molecular mechanical approach to evaluate whether a water molecule present in the active site might act as a nucleophile upon formation of the new C−O bond, a hypothesis recently suggested in the literature. Our study shows that activation of H2O can be favoured by the presence of the Mo=Oeq group. However, overall our results suggest that mechanisms other than the nucleophilic attack by Mo=Oeq to the activated carbon of the CO substrate are not likely to constitute reactive channels for the oxidation of CO by the enzyme.
|
|
| 5. |
- Rovaletti, Anna, et al.
(författare)
-
How general is the effect of the bulkiness of organic ligands on the basicity of metal-organic catalysts? H2-evolving Mo oxides/sulphides as case studies
- 2022
-
Ingår i: Physical chemistry chemical physics : PCCP. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 24:48, s. 29471-29479
-
Tidskriftsartikel (refereegranskat)abstract
- Tailoring the activity of an organometallic catalyst usually requires a targeted ligand design. Tuning the ligand bulkiness and tuning the electronic properties are popular approaches, which are somehow interdependent because substituents of different sizes within ligands can determine inter alia the occurrence of different degrees of inductive effects. Ligand basicity, in particular, turned out to be a key property for the modulation of protonation reactions occurring in vacuo at the metals in complexes bearing organophosphorus ligands; however, when the same reactions take place in a polar organic solvent, their energetics becomes dependent on the trade-off between ligand basicity and bulkiness, with the polarity of the solvent playing a key role in this regard [Bancroft et al., Inorg. Chem., 1986, 25, 3675; Rovaletti et al., J. Phys. Org. Chem., 2018, 31, e3748]. In the present contribution, we carried out molecular dynamics and density functional theory calculations on water-soluble Mo-based catalysts for proton reduction, in order to study the energetics of protonation reactions in complexes where the incipient proton binds a catalytically active ligand (i.e., an oxide or a disulphide). We considered complexes either soaked in water or in a vacuum, and featuring N-based ancillary ligands of different bulkiness (i.e. cages constituted either by pyridine or isoquinoline moieties). Our results show that the energetics of protonation events can be affected by ancillary ligand bulkiness even when the metal center does not play the role of the H+ acceptor. In vacuo, protonation at the O or S atom in the α position relative to the metal in complexes featuring the bulky isoquinoline-based ligand is more favored by around 10 kcal mol−1 when compared to the case of the pyridine-based counterparts, a difference that is almost zero when the same reactions occur in water. Such an outcome is rationalized in light of the different electrostatic properties of complexes bearing ancillary ligands of different sizes. The overall picture from theory indicates that such effects of ligand bulkiness can be relevant for the design of green chemistry catalysts that undergo protonation steps in water solutions.
|
|
| 6. |
- Rovaletti, Anna, et al.
(författare)
-
Theoretical insights into the aerobic hydrogenase activity of molybdenum-copper CO dehydrogenase
- 2019
-
Ingår i: Inorganics. - : MDPI AG. - 2304-6740. ; 7:11
-
Tidskriftsartikel (refereegranskat)abstract
- The Mo/Cu-dependent CO dehydrogenase from O. carboxidovorans is an enzyme that is able to catalyse CO oxidation to CO2; moreover, it also expresses hydrogenase activity, as it is able to oxidize H2. Here, we have studied the dihydrogen oxidation catalysis by this enzyme using QM/MM calculations. Our results indicate that the equatorial oxo ligand of Mo is the best suited base for catalysis. Moreover, extraction of the first proton from H2 by means of this basic centre leads to the formation of a Mo–OH–CuIH hydride that allows for the stabilization of the copper hydride, otherwise known to be very unstable. In light of our results, two mechanisms for the hydrogenase activity of the enzyme are proposed. The first reactive channel depends on protonation of the sulphur atom of a Cu-bound cysteine residues, which appears to favour the binding and activation of the substrate. The second reactive channel involves a frustrated Lewis pair, formed by the equatorial oxo group bound to Mo and by the copper centre. In this case, no binding of the hydrogen molecule to the Cu center is observed but once H2 enters into the active site, it can be split following a low-energy path.
|
|
