Computational Studies of the Reaction Mechanisms Of Methyl Coenzyme M Reductase, [FeFe]-Hydrogenase And Rh-LmrR

Enzymes are proteins that are Nature’s catalysts and have evolved to catalyze some of the most energy-demanding reactions in nature. Their evolutionary advantage has allowed them to employ mechanisms that are much more efficient and inexpensive than current industrial processes. Because of this, understanding how enzymes work is critical in the development of better catalytic processes. In the work reported here, I will focus on studies on enzymatic mechanisms using computational chemistry tools, demonstrating how different aspects of the complexity imposed by the enzyme can be studied at different scales. The importance of these three systems lies in their ability to facilitate reactions that are critical in energy applications: [FeFe]-Hydrogenase is an enzyme that reversibly and efficiently interconverts protons (H+) and electrons (e−) to molecular hydrogen (H2); Methyl Coenzyme-M Reduc- tase (MCR) is the enzyme responsible for methane formation and oxidation; the Rh-LmrR artificial enzyme is able to hydrogenate CO2 to formate (HCOO−). This work highlights several different aspects of how the protein environment in enzymes beyond the active site modulates different aspects of the catalytic mechanisms. In MCR, the protein environment assists in the positioning of substrates in the active site pocket, revealing the possibility of an alternative mechanism that eliminates the need for the rearrangement of substrates. In [FeFe]-Hydrogenase the protein environment modulates the catalytic bias by stabilizing the desired electronic states of the cofactors and influences activity by changing the ability of the protein transport network to move protons via a thermodynamic gradient. Finally, in the artificial enzyme Rh-LmrR we reveal how the dynamics of both the scaffold and the solvent can influence activity by modulating the electronic environment in the active site, the delivery of the CO2 substrate, and changing the access to water. Collectively, these studies demonstrated the importance of carefully considering the role of the broader protein and solvent environment and the need to incorporate some of these features as transferable design principles in the development of synthetic catalysts for energy applications

Splitting of multiple hydrogen molecules by bioinspired diniobium metal complexes: a DFT study

Splitting of molecular hydrogen (H2) into bridging and terminal hydrides is a common step in transition metal chemistry. Herein, we propose a novel organometallic platform for cleavage of multiple H2 molecules, which combines metal centers capable of stabilizing multiple oxidation states, and ligands bearing positioned pendant basic groups. Using quantum chemical modeling, we show that low-valent, early transition metal diniobium(II) complexes with diphosphine ligands featuring pendant amines can favorably uptake up to 8 hydrogen atoms, and that the energetics are favored by the formation of intramolecular dihydrogen bonds. This result suggests new possible strategies for the development of hydrogen scavenger molecules that are able to perform reversible splitting of multiple H2 molecules

Structural Characterization of the P1+ Intermediate State of the P-Cluster of Nitrogenase

Nitrogenase is the enzyme that reduces atmospheric dinitrogen (N2) to ammonia (NH3) in biological systems. It catalyzes a series of single-electron transfers from the donor iron protein (Fe protein) to the molybdenum–iron protein (MoFe protein) that contains the iron–molybdenum cofactor (FeMo-co) sites where N2 is reduced to NH3. The P-cluster in the MoFe protein functions in nitrogenase catalysis as an intermediate electron carrier between the external electron donor, the Fe protein, and the FeMo-co sites of the MoFe protein. Previous work has revealed that the P-cluster undergoes redox-dependent structural changes and that the transition from the all-ferrous resting (PN) state to the two-electron oxidized P2+ state is accompanied by protein serine hydroxyl and backbone amide ligation to iron. In this work, the MoFe protein was poised at defined potentials with redox mediators in an electrochemical cell, and the three distinct structural states of the P-cluster (P2+, P1+, and PN) were characterized by X-ray crystallography and confirmed by computational analysis. These analyses revealed that the three oxidation states differ in coordination, implicating that the P1+ state retains the serine hydroxyl coordination but lacks the backbone amide coordination observed in the P2+ states. These results provide a complete picture of the redox-dependent ligand rearrangements of the three P-cluster redox states

Heterolytic Scission of Hydrogen Within a Crystalline Frustrated Lewis Pair

We report the heterolysis of molecular hydrogen under ambient conditions by the crystalline frustrated Lewis pair (FLP) 1-{2-[bis (pentafluorophenyOboryl] phenyl -2, 2,6,6-tetrame-thylpiperidine (KCAT). The gas-solid reaction provides an approach to prepare the solvent-free, polycrystalline ion pair KCATH2 through a single crystal to single crystal transformation. The crystal lattice of KCATH2 increases in size relative to the parent KCAT by approximately 2%. Microscopy was used to follow the transformation of the highly colored red/orange KCAT to the colorless KCATH2 over a period of 2 h at 300 K under a flow of H-2 gas. There is no evidence of crystal decrepitation during hydrogen uptake. Inelastic neutron scattering employed over a temperature range from 4-200 K did not provide evidence for the formation of polarized H-2 in a precursor complex within the crystal at low temperatures and high pressures. However, at 300 K, the INS spectrum of KCAT transformed to the INS spectrum of KCATH2. Calculations suggest that the driving force is more favorable in the solid state compared to the solution or gas phase, but the addition of H-2 into the KCAT crystal is unfavorable. Ab Initio methods were used to calculate the INS spectra of KCAT, KCATH2, and a possible precursor complex of H-2 in the pocket between the B and N of crystalline KCAT. Ex-situ NMR showed that the transformation from KCAT to KCATH2 is quantitative and our results suggest that the hydrogen heterolysis process occurs via H-2 diffusion into the FLP crystal with a rate-limiting movement of H-2 from inactive positions to reactive sites.Peer reviewe

Computational study of chemical reactions

Computers can be used to obtain detailed pictures of chemical reactions. A brief overview of a number of computational approaches which can be used to this end will be given. Computational advantages and disadvantages of selected algorithms will be discussed, as well as their applicability and their accuracy. Application of some of the methods will be presented in a study of the reaction of hydrogen peroxide and hydroxyl radical (i.e H2O2 + OH→H2O + O2H). The reaction was studied in gas as well as in condensed phase. In the gas phase two distinct reaction pathways were identified, and the rate was calculated using variational transition state theory for a temperature range of 250-500 K. The calculations explain how the unusual temperature dependence observed for temperatures above 900 K is due to the reaction occurring on the low-lying excited state surface, rather than on the ground state surface. In solution, the reaction is studied using the QM/MM methodology. The free energy barrier was found to be higher than the barrier in the gas phase, which is in accord with the experimental findings of the rate being slower in solution. This work demonstrates the power of computational studies to explain and predict characteristics of chemical reactions, as well as interpret experimental observations

Biochemistry of Methyl-Coenzyme M Reductase

Methanogens are masters of CO2 reduction. They conserve energy by coupling H2 oxidation to the reduction of CO2 to CH4, the primary constituent of natural gas. They also generate methane by the reduction of acetic acid, methanol, methane thiol, and methylamines. Methanogens produce 109 tons of methane per year and are the major source of the earth’s atmospheric methane. Reverse methanogenesis or anaerobic methane oxidation, which is catalyzed by methanotrophic archaea living in consortia among bacteria that can act as an electron acceptor, is responsible for annual oxidation of 108 tons of methane to CO2. This chapter briefly describes the overall process of methanogenesis and then describes the enzymatic mechanism of the nickel enzyme, methyl-CoM reductase (MCR), the key enzyme in methane synthesis and oxidation. MCR catalyzes the formation of methane and the heterodisulfide (CoBSSCoM) from methyl-coenzyme M (methyl-CoM) and coenzyme B (HSCoB). Uncovering the mechanistic and molecular details of MCR catalysis is critical since methane is an abundant and important fuel and is the second (to CO2) most prevalent greenhouse gas.</jats:p

Modeling the Reaction of Fe Atoms with CCl₄

The reaction of iron atoms with carbon tetrachloride (CCl4) in gas phase was studied using density functional theory. A recent experimental study (Parkinson, G. S.; Dohnálek, Z.; Smith, R. S.; Kay, B. D. J. Phys. Chem. C 2009, 113, 1818) of this reaction, performed by dropping Fe atoms into CCl4 deposited on a cold FeO(111) surface, demonstrates rich chemistry with several products (C2Cl4, C2Cl6, OCCl2, CO, FeCl2, and FeCl3) observed. The reactions of Fe with CCl4 was studied under three stoichiometries, one Fe with one CCl4, one Fe with two CCl4 molecules, and two Fe with one CCl4, modeling the stoichiometric, CCl4-rich, and Fe-rich environments of the experimental work. The electronic structure calculations give insight into the reactions leading to the experimentally observed products, in particular with regard to the formation of FeCl3 and other oxygen containing compounds that are not predicted from the simplest reactive model of successive Cl atom abstractions. They rather suggest that novel Fe−C−Cl containing species are important intermediates in these reactions. The intermediate complexes are formed in highly exothermic reactions, in agreement with the experimentally observed reactivity on the surface at low temperature (30 K). This initial survey of the reactivity of Fe with CCl4 identifies some potential reaction pathways that are important in the effort to use Fe nanoparticles to differentiate harmful pathways that lead to the formation of contaminants like chloroform (CHCl3) from harmless pathways that lead to products such as formate (HCO2−) or carbon oxides in water and soil