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The nonheme iron dioxygenase deoxypodophyllotoxin synthase performs an oxidative ring-closure reaction as part of natural product synthesis in plants. How the enzyme enables the oxidative ring-closure reaction of (-)-yatein and avoids substrate hydroxylation remains unknown. To gain insight into the reaction mechanism and understand the details of the pathways leading to products and by-products we performed a comprehensive computational study. The work shows that substrate is bound tightly into the substrate binding pocket with the C7'-H bond closest to the iron(IV)-oxo species. The reaction proceeds through a radical mechanism starting with hydrogen atom abstraction from the C7'-H position followed by ring-closure and a final hydrogen transfer to form iron(II)-water and deoxypodophyllotoxin. Alternative mechanisms including substrate hydroxylation and an electron transfer pathway were explored but found to be higher in energy. The mechanism is guided by electrostatic perturbations of charged residues in the second-coordination sphere that prevent alternative pathways. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide is a versatile reductant that under the right conditions can react to form dioxygen in an electrochemical reaction. This reaction has a low carbon footprint and applications are being sought for batteries. In this work a computational study is presented on a recently reported nonheme iron(II) complex where we study mechanistic pathways leading to dioxygen formation from H2O2. The work shows that upon reduction of the iron(III)‐hydroperoxo species it rapidly leads through heterolytic cleavage of the dioxygen bond to form iron(IV)‐oxo(hydroxo). The dimerization reaction of two iron(IV)‐oxo(hydroxo) complexes then leads to formation of the dioxygen bond rapidly with small barriers. Dissociation of the dimer expels dioxygen in an exothermic reaction. An alternative mechanism through the formation of a μ‐1,2‐peroxo‐μ‐1,1‐hydroperoxodiiron(II) intermediate was also tested but found to be highly endergonic. These studies highlight the electrochemical feasibilities of nonheme iron(III)‐hydroperoxo complexes. [ABSTRACT FROM AUTHOR]

CO2 utilization is an important process in the chemical industry with great environmental power. In this work we show how CO2 and H2 can be reacted to form methanol on an iron(II) center and highlight the bottlenecks for the reaction and what structural features of the catalyst are essential for efficient turnover. The calculations predict the reactions to proceed through three successive reaction cycles that start with heterolytic cleavage of H2 followed by sequential hydride and proton transfer processes. The H2 splitting process is an endergonic process and hence high pressures will be needed to overcome this step and trigger the hydrogenation reaction. Moreover, H2 cleavage into a hydride and proton requires a metal to bind hydride and a nearby source to bind the proton, such as an amide or pyrazolyl group, which the scorpionate ligand used here facilitates. As such the computations highlight the non‐innocence of the ligand scaffold through proton shuttle from H2 to substrate as an important step in the reaction mechanism. [ABSTRACT FROM AUTHOR]

High‐valent metal‐oxo species play critical roles in enzymatic catalysis yet their properties are still poorly understood. In this work we report a combined experimental and computational study into biomimetic iron(IV)‐oxo and iron(III)‐oxo complexes with tight second‐coordination sphere environments that restrict substrate access. The work shows that the second‐coordination sphere slows the hydrogen atom abstraction step from toluene dramatically and the kinetics is zeroth order in substrate. However, the iron(II)‐hydroxo that is formed has a low reduction potential and hence cannot do OH rebound favorably. The tolyl radical in solution then reacts further with alternative reaction partners. By contrast, the iron(IV)‐oxo species reacts predominantly through OH rebound to form alcohol products. Our studies show that the oxidation state of the metal influences reactivities and selectivities with substrate dramatically and that enzymes will likely need an iron(IV) center to catalyze C−H hydroxylation reactions. [ABSTRACT FROM AUTHOR]

High‐valent iron(IV)‐oxo intermediates are versatile oxidants in the biotransformation of various substrates by metalloenzymes and catalyze essential reactions for human health as well as in the biodegradation of toxic organic pollutants in the environment. Herein, we report a biomimetic system that efficiently reacts with halophenols through defluorination reactions and characterize various short‐lived intermediates along the reaction mechanism. We study the reactivity pattern of a nonheme iron(IV)‐oxo species with a series of trihalophenols (X=F, Cl, Br). A combined experimental and computational study reveals that the oxidative dehalogenation of 2,4,6‐trifluorophenol is initiated with an H‐atom abstraction from the phenolic group by the iron(IV)‐oxo species resulting in the formation of a phenolate radical and an iron(III)‐hydroxo species. This iron(III)‐hydroxo species forms an adduct with the oxidized substrate with λmax at 558 nm which subsequently decays to give quinones as products. [ABSTRACT FROM AUTHOR]

Taurine/α‐ketoglutarate dioxygenase is an important enzyme that takes part in the cysteine catabolism process in the human body and selectively hydroxylates taurine at the C1‐position. Recent computational studies showed that in the gas‐phase the C2−H bond of taurine is substantially weaker than the C1−H bond, yet no evidence exists of 2‐hydroxytaurine products. To this end, a detailed computational study on the selectivity patterns in TauD was performed. The calculations show that the second‐coordination sphere and the protonation states of residues play a major role in guiding the enzyme to the right selectivity. Specifically, a single proton on an active site histidine residue can change the regioselectivity of the reaction through its electrostatic perturbations in the active site and effectively changes the C1−H and C2−H bond strengths of taurine. This is further emphasized by many polar and hydrogen bonding interactions of the protein cage in TauD with the substrate and the oxidant that weaken the pro‐R C1−H bond and triggers a chemoselective reaction process. The large cluster models reproduce the experimental free energy of activation excellently. [ABSTRACT FROM AUTHOR]

Aryloxyalkanoate dioxygenases are unique herbicide biodegrading nonheme iron enzymes found in plants and hence, from environmental and agricultural point of view they are important and valuable. However, they often are substrate specific and little is known on the details of the mechanism and the substrate scope. To this end, we created enzyme models and calculate the mechanism for 2,4‐dichlorophenoxyacetic acid biodegradation and 2‐methyl substituted analogues by density functional theory. The work shows that the substrate binding is tight and positions the aliphatic group close to the metal center to enable a chemoselective reaction mechanism to form the C2‐hydroxy products, whereas the aromatic hydroxylation barriers are well higher in energy. Subsequently, we investigated the metabolism of R‐ and S‐methyl substituted inhibitors and show that these do not react as efficiently as 2,4‐dichlorophenoxyacetic acid substrate due to stereochemical clashes in the active site and particularly for the R‐isomer give high rebound barriers. [ABSTRACT FROM AUTHOR]

Thiol dioxygenases are important enzymes for human health; they are involved in the detoxification and catabolism of toxic thiol‐containing natural products such as cysteine. As such, these enzymes have relevance to the development of Alzheimer's and Parkinson's diseases in the brain. Recent crystal structure coordinates of cysteine and 3‐mercaptopropionate dioxygenase (CDO and MDO) showed major differences in the second‐coordination spheres of the two enzymes. To understand the difference in activity between these two analogous enzymes, we created large, active‐site cluster models. We show that CDO and MDO have different iron(III)‐superoxo‐bound structures due to differences in ligand coordination. Furthermore, our studies show that the differences in the second‐coordination sphere and particularly the position of a positively charged Arg residue results in changes in substrate positioning, mobility and enzymatic turnover. Furthermore, the substrate scope of MDO is explored with cysteinate and 2‐mercaptosuccinic acid and their reactivity is predicted. [ABSTRACT FROM AUTHOR]

The quantum calculation gives the insight of reaction mechanism in chemistry. In this work, we predict hydrogen evolution reaction (HER) mechanism in Ni(abt)2 (abt = 2‐aminobenzenethiolate) catalyst. Using density functional theory (DFT) and coupled‐cluster singles, doubles and perturbative triples (CCSD(T)) methods, we demonstrate the potential energy surface (PES) for the HER reaction result with two intermediate states (IM) and transition states (TS). Our result shows that the hydrogen atoms are migrated to Ni atom one by one from each of two amino groups. It indicates that the HER reaction in Ni(abt)2 occurs following the ligand‐assisted metal‐centered H2 production. Finally, two hydrogen atoms are merged in Ni atom site which generates hydrogen molecule. This would be meaningful prediction to understand the role of metal catalyst in HER reaction pathway. [ABSTRACT FROM AUTHOR]

This article, titled "Mechanism of CO2 Reduction to Methanol with H2 on an Iron(II)-scorpionate Catalyst," explores the reaction mechanism of a homogeneous catalyst that binds H2 and CO2 on an iron(II)-scorpionate complex. Through calculations, it is determined that the iron complex can cleave H2 into a hydride and proton, which then bind to different sites on the complex. CO2 is subsequently reduced through a series of hydride and proton transfer steps, ultimately resulting in the formation of methanol products. The full research article provides more detailed information on this topic. [Extracted from the article]