Density Functional Theory Study into the Reaction Mechanism of Isonitrile Biosynthesis by the Nonheme Iron Enzyme ScoE

AbstractThe nonheme iron enzyme ScoE catalyzes the biosynthesis of an isonitrile substituent in a peptide chain. To understand details of the reaction mechanism we created a large active site cluster model of 212 atoms that contains substrate, the active oxidant and the first- and second-coordination sphere of the protein and solvent. Several possible reaction mechanisms were tested and it is shown that isonitrile can only be formed through two consecutive catalytic cycles that both use one molecule of dioxygen and α-ketoglutarate. In both cycles the active species is an iron(IV)-oxo species that in the first reaction cycle reacts through two consecutive hydrogen atom abstraction steps: first from the N–H group and thereafter from the C–H group to desaturate the NH-CH2 bond. The alternative ordering of hydrogen atom abstraction steps was also tested but found to be higher in energy. Moreover, the electronic configurations along that pathway implicate an initial hydride transfer followed by proton transfer. We highlight an active site Lys residue that is shown to donate charge in the transition states and influences the relative barrier heights and bifurcation pathways. A second catalytic cycle of the reaction of iron(IV)-oxo with desaturated substrate starts with hydrogen atom abstraction followed by decarboxylation to give isonitrile directly. The catalytic cycle is completed with a proton transfer to iron(II)-hydroxo to generate the iron(II)-water resting state. The work is compared with experimental observation and previous computational studies on this system and put in a larger perspective of nonheme iron chemistry.

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Isolation of a Bimetallic Cobalt(III) Nitride and Examination of its Hydrogen Atom Abstraction Chemistry and Reactivity Towards H2

10.26434/chemrxiv.11562144 ◽

2020 ◽

Author(s):

Debabrata Sengupta ◽

Christian Sandoval-Pauker ◽

Emily Schueller ◽

Angela M. Encerrado-Manriquez ◽

Alejandro J. Metta-Magaña ◽

...

Keyword(s):

Hydrogen Atom ◽

Density Functional ◽

Room Temperature ◽

Hydrogen Atom Abstraction ◽

Functional Theory ◽

Kinetic Rate ◽

Rate Analysis ◽

Stable Product ◽

Activation Pathways ◽

Computational Analyses

Room temperature photolysis of the bis(azide)cobaltate(II) complex [Na(THF)x][(ketguan)Co(N3)2] (ketguan = [(tBu2CN)C(NDipp)2]–, Dipp = 2,6-diisopropylphenyl) (3a) in THF cleanly forms the binuclear cobalt nitride [Na(THF)4{[(ketguan)Co(N3)]2(μ-N)}]n (1). Compound 1 represents the first example of an isolable, bimetallic cobalt nitride complex, and it has been fully characterized by spectroscopic, magnetic, and computational analyses. Density functional theory supports a CoIII=N=CoIII canonical form with significant π-bonding between the cobalt centers and the nitride atom. Unlike other Group 9 bridging nitride complexes, no radical character is detected at the bridging N-atom of 1. Indeed, 1 is unreactive towards weak C-H donors and even co-crystallizes with a molecule of cyclohexadiene (CHD) in its crystallographic unit cell to give 1·CHD as a room temperature stable product. Notably, addition of pyridine to 1 or photolyzed solutions of [(ketguan)Co(N3)(py)]2 (4a) leads to destabilization via activation of the nitride unit, resulting in the mixed-valent Co(II)/(III) bridged imido species [(ketguan)Co]2(μ-NH)(μ-N3) (5) formed from intermolecular hydrogen atom abstraction (HAA) of strong C-H bonds (BDE ~ 100 kcal/mol). Kinetic rate analysis of the formation of 5 in the presence of C6H12 or C6D12 gives a KIE = 2.5±0.1, supportive of a HAA formation path-way. The reactivity of our system was further probed by photolyzing C6D6/py-d5 solutions of 4a under an H2 atmosphere (150 psi), which leads to the exclusive formation of the bis(imido)[(ketguan)Co(μ-NH)]2 (6) as a result of dihydrogen activa-tion. These results provide unique insights into the chemistry and electronic structure of late 3d-metal nitrides while providing entryway into C-H activation pathways.

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DFT Investigation of Hydrogen Atom Abstraction from NHC-Boranes by Methyl, Ethyl and Cyanomethyl Radicals—Composition and Correlation Analysis of Kinetic Barriers

Molecules ◽

10.3390/molecules25194509 ◽

2020 ◽

Vol 25 (19) ◽

pp. 4509

Author(s):

Hong-jie Qu ◽

Lang Yuan ◽

Cai-xin Jia ◽

Hai-tao Yu ◽

Hui Xu

Keyword(s):

Free Energy ◽

Hydrogen Atom ◽

Gibbs Free Energy ◽

Density Functional ◽

Vibrational Energy ◽

Hydrogen Atom Abstraction ◽

Reaction Energy ◽

Energy Barriers ◽

Energy Correction ◽

Kinetic Barriers

Understanding the hydrogen atom abstraction (HAA) reactions of N-heterocyclic carbene (NHC)-boranes is essential for extending the practical applications of boron chemistry. In this study, density functional theory (DFT) computations were performed for the HAA reactions of a series of NHC-boranes attacked by •CH2CN, Me• and Et• radicals. Using the computed data, we investigated the correlations of the activation and free energy barriers with their components, including the intrinsic barrier, the thermal contribution of the thermodynamic reaction energy to the kinetic barriers, the activation Gibbs free energy correction and the activation zero-point vibrational energy correction. Furthermore, to describe the dependence of the activation and free energy barriers on the thermodynamic reaction energy or reaction Gibbs free energy, we used a three-variable linear model, which was demonstrated to be more precise than the two-variable Evans–Polanyi linear free energy model and more succinct than the three-variable Marcus-theory-based nonlinear HAA model. The present work provides not only a more thorough understanding of the compositions of the barriers to the HAA reactions of NHC-boranes and the HAA reactivities of the substrates but also fresh insights into the suitability of various models for describing the relationships between the kinetic and thermodynamic physical quantities.

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Selective Hydrogen Atom Abstraction from Dihydroflavonol by a Nonheme Iron Center Is the Key Step in the Enzymatic Flavonol Synthesis and Avoids Byproducts

Journal of the American Chemical Society ◽

10.1021/jacs.9b10526 ◽

2019 ◽

Vol 141 (51) ◽

pp. 20278-20292 ◽

Cited By ~ 19

Author(s):

Sidra Ghafoor ◽

Asim Mansha ◽

Sam P. de Visser

Keyword(s):

Hydrogen Atom ◽

Nonheme Iron ◽

Hydrogen Atom Abstraction ◽

Iron Center

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Properties and reactivities of nonheme iron(iv)–oxo versus iron(v)–oxo: long-range electron transfer versus hydrogen atom abstraction

Physical Chemistry Chemical Physics ◽

10.1039/c4cp03053b ◽

2014 ◽

Vol 16 (41) ◽

pp. 22611-22622 ◽

Cited By ~ 4

Author(s):

Baharan Karamzadeh ◽

Devendra Singh ◽

Wonwoo Nam ◽

Devesh Kumar ◽

Sam P. de Visser

Keyword(s):

Electron Transfer ◽

Hydrogen Atom ◽

Long Range ◽

Cation Radical ◽

Nonheme Iron ◽

Hydrogen Atom Abstraction ◽

Computational Studies ◽

Radical Species ◽

Oxo Ligand

Computational studies show that the perceived nonheme iron(v)–oxo is actually an iron(iv)–oxo ligand cation radical species.

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Kinetics of Hydrogen Atom Abstraction from Substrate by an Active Site Thiyl Radical in Ribonucleotide Reductase

Journal of the American Chemical Society ◽

10.1021/ja507313w ◽

2014 ◽

Vol 136 (46) ◽

pp. 16210-16216 ◽

Cited By ~ 23

Author(s):

Lisa Olshansky ◽

Arturo A. Pizano ◽

Yifeng Wei ◽

JoAnne Stubbe ◽

Daniel G. Nocera

Keyword(s):

Hydrogen Atom ◽

Ribonucleotide Reductase ◽

Active Site ◽

Hydrogen Atom Abstraction ◽

Thiyl Radical ◽

Kinetics Of

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Sustainable Option for Hydrogen Production: Mechanistic Study of the Interaction between Cobalt Pincer Complexes and Ammonia Borane

Catalysts ◽

10.3390/catal10070723 ◽

2020 ◽

Vol 10 (7) ◽

pp. 723

Author(s):

Yan Li ◽

Chi-Wing Tsang ◽

Eve Man Hin Chan ◽

Eugene Yin Cheung Wong ◽

Danny Chi Kuen Ho ◽

...

Keyword(s):

Proton Transfer ◽

Density Functional ◽

Ammonia Borane ◽

Active Species ◽

Cobalt Catalysts ◽

Mechanistic Study ◽

Iridium Complexes ◽

Concerted Mechanism ◽

Ru Complexes ◽

Reaction Barriers

The mechanism of the solvolysis/hydrolysis of ammonia borane by iridium (Ir), cobalt (Co), iron (Fe) and ruthenium (Ru) complexes with various PNP ligands has been revisited using density functional theory (DFT). The approach of ammonia borane (NH3BH3) to the metal center has been tested on three different possible mechanisms, namely, the stepwise, concerted and proton transfer mechanism. It was found that the theoretical analyses correlate with the experimental results very well, with the activities of the iridium complexes with different PNP ligands following the order: (tBu)2P > (iPr)2P > (Ph)2P through the concerted mechanism. The reaction barriers of the rate-determining steps for the dehydrogenation of ammonia borane catalyzed by the active species [(tBu)2PNP-IrH] (Complex I-8), are found to be 19.3 kcal/mol (stepwise), 15.2 kcal/mol (concerted) and 26.8 kcal/mol (proton transfer), respectively. Thus, the concerted mechanism is the more kinetically favorable pathway. It is interesting to find that stable (tBu)2PNP Co-H2O and (tBu)2PNP Co-NH3 chelation products exist, which could stabilize the active I-8 species during the hydrolysis reaction cycle. The use of more sterically hindered and electron-donating PNP ligands such as (adamantyl)2P- provides similar activity as the t-butyl analogue. This research provides insights into the design of efficient cobalt catalysts instead of using precious and noble metal, which could benefit the development of a more sustainable hydrogen economy.

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Bimolecular reactions of distonic ions: Proton transfer and hydrogen atom abstraction with˙CH2OH2+

Organic Mass Spectrometry ◽

10.1002/oms.1210281019 ◽

1993 ◽

Vol 28 (10) ◽

pp. 1098-1100 ◽

Cited By ~ 21

Author(s):

Philippe Mourgues ◽

Henri Edouard Audier ◽

Danielle Leblanc ◽

Steen Hammerum

Keyword(s):

Hydrogen Atom ◽

Proton Transfer ◽

Hydrogen Atom Abstraction ◽

Bimolecular Reactions ◽

Distonic Ions

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Dual-Function Enzyme Catalysis for Enantioselective Carbon–Nitrogen Bond Formation

10.26434/chemrxiv.14452158.v1 ◽

2021 ◽

Author(s):

zhen liu ◽

Carla Calvó-Tusell ◽

Andrew Z. Zhou ◽

kai chen ◽

Marc Garcia-Borràs ◽

...

Keyword(s):

Proton Transfer ◽

Active Site ◽

Density Functional ◽

Dual Function ◽

Cytochrome P450 Enzymes ◽

Active Site Residues ◽

Bond Forming ◽

Enzymatic Transformation ◽

Excellent Activity ◽

Dynamics Simulations

Whereas enzymatic asymmetric carbene N–H insertion is a powerful method for preparation of chiral amines in principle, it has suffered from limited enantioselectivity in practice. In this work, we demonstrate that engineered cytochrome P450 enzymes can catalyze this abiological C–N bond-forming reaction with excellent activity and selectivity (up to 32,100 TTN, >99% yield and 98% e.e.) to prepare a series of bioactive α-amino lactones, which have not been accessed previously using a carbene insertion strategy. The enzymes are dual-function catalysts, effecting both carbene transfer and enantioselective proton-transfer catalysis, in a single active site. To gain insight into the mechanism of the enzymatic transformation, especially in the asymmetric protonation step, we performed extensive molecular dynamics simulations and density functional theory (DFT) calculations. Computational studies uncover the important roles of active-site residues that enable high activity and selectivity through interacting with the carbene intermediate and the amine substrate, and directing water molecules for selective proton transfer.

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