A Theory for Bioinorganic Chemical Reactivity of Oxometal Complexes and Analogous Oxidants: The Exchange and Orbital-Selection Rules

Over the past decades metalloenzymes and their synthetic models have emerged as an area of increasing research interest. The metalloenzymes and their synthetic models oxidize organic molecules using oxometal complexes (OMCs), especially oxoiron(IV)-based ones. Theoretical studies have helped researchers to characterize the active species and to resolve mechanistic issues. This activity has generated massive amounts of data on the relationship between the reactivity of OMCs and the transition metal’s identity, oxidation state, ligand sphere, and spin state. Theoretical studies have also produced information on transition state (TS) structures, reaction intermediates, barriers, and rate–equilibrium relationships. For example, the experimental–theoretical interplay has revealed that nonheme enzymes carry out H-abstraction from strong C–H bonds using high-spin (S = 2) oxoiron(IV) species with four unpaired electrons on the iron center. However, other reagents with higher spin states and more unpaired electrons on the metal are not as reactive. Still other reagents carry out these transformations using lower spin states with fewer unpaired electrons on the metal. The TS structures for these reactions exhibit structural selectivity depending on the reactive spin states. The barriers and thermodynamic driving forces of the reactions also depend on the spin state. H-Abstraction is preferred over the thermodynamically more favorable concerted insertion into C–H bonds. Currently, there is no unified theoretical framework that explains the totality of these fascinating trends.This Account aims to unify this rich chemistry and understand the role of unpaired electrons on chemical reactivity. We show that during an oxidative step the d-orbital block of the transition metal is enriched by one electron through proton-coupled electron transfer (PCET). That single electron elicits variable exchange interactions on the metal, which in turn depend critically on the number of unpaired electrons on the metal center. Thus, we introduce the exchange-enhanced reactivity (EER) principle, which predicts the preferred spin state during oxidation reactions, the dependence of the barrier on the number of unpaired electrons in the TS, and the dependence of the deformation energy of the reactants on the spin state. We complement EER with orbital-selection rules, which predict the structure of the preferred TS and provide a handy theory of bioinorganic oxidative reactions. These rules show how EER provides a Hund’s Rule for chemical reactivity: EER controls the reactivity landscape for a great variety of transition-metal complexes and substrates. Among many reactivity patterns explained, EER rationalizes the abundance of high-spin oxoiron(IV) complexes in enzymes that carry out bond activation of the strongest bonds. The concepts used in this Account might also be applicable in other areas such as in f-block chemistry and excited-state reactivity of 4d and 5d OMCs

Highly Chemoselective and Enantioselective Catalytic Oxidation of Heteroaromatic Sulfides via High-Valent Manganese(IV)–Oxo Cation Radical Oxidizing Intermediates

A manganese complex with a porphyrin-like ligand that catalyzes the highly chemoselective and enantioselective oxidation of heteroaromatic sulfides, including imidazole, benzimidazole, indole, pyridine, pyrimidine, pyrazine, <i>sym</i>-triazine, thiophene, thiazole, benzothiazole, and benzoxazole, with hydrogen peroxide is described, furnishing the corresponding sulfoxides in good to excellent yields and enantioselectivities (up to 90% yield and up to >99% ee) within a short reaction time (0.5 h). The practical utility of the method has been demonstrated in the gram-scale synthesis of chiral sulfoxide. Mechanistic studies, performed with ¹⁸O-labeled water (H₂¹⁸O), hydrogen peroxide (H₂¹⁸O₂), and cumyl hydroperoxide, reveal that a high-valent manganese–oxo species is generated as the oxygen atom delivering agent via carboxylic acid assisted heterolysis of O–O bonds. Density functional theory (DFT) calculations were also carried out to give further insight into the mechanism of manganese-catalyzed sulfoxidation. On the basis of the theoretical study, the coupled high-valent manganese­(IV)–oxo cation radical species, which bears obvious similarities with that of reactive intermediates in the catalytic oxygenation reactions based on the cytochrome P450 and metalloporphyrin models, has been proposed as the reactive oxidant in the non-heme manganese catalyst system

The Fe^III(H₂O₂) Complex as a Highly Efficient Oxidant in Sulfoxidation Reactions: Revival of an Underrated Oxidant in Cytochrome P450

This work demonstrates that the Fe^III(H₂O₂) complex, which has been considered as an unlikely oxidant in P450, is actually very efficient in sulfoxidation reactions. Thus, Fe^III(H₂O₂) undergoes a low-barrier nucleophilic attack by sulfur on the distal oxygen, <i>resulting in heterolytic O–O cleavage coupled to proton transfer</i>. We further show that Fe^III(H₂O₂) is an efficient sulfoxidation catalyst in synthetic iron porphyrin and iron corrolazine compounds. In all cases, Fe^III(H₂O₂) performs the oxidation <i>much faster than it converts to Cpd I</i> and will therefore bypass Cpd I in the presence of a thioether. Thus, this paper not only suggests a plausible resolution of a longstanding issue in P450 chemistry regarding the “second oxidant” but also highlights a new mechanistic pathway for sulfoxidation reactions in P450s and their multitude of synthetic analogues. These findings have far-reaching implications for transition metal compounds, where H₂O₂ is used as the terminal oxidant

Rhodium-Catalyzed Azide–Alkyne Cycloaddition of Internal Ynamides: Regioselective Assembly of 5‑Amino-Triazoles under Mild Conditions

A rhodium-catalyzed azide–alkyne cycloaddition of internal ynamides is described. The reaction could be performed in a wide range of solvents, including aqueous media, under mild conditions without careful exclusion of air and moisture, giving a variety of 5-amino-triazoles as a single regioisomer. The mechanism of regioselective cycloaddition was rationalized by means of density functional theory calculations

Selective Chlorination of Substrates by the Halogenase SyrB2 Is Controlled by the Protein According to a Combined Quantum Mechanics/Molecular Mechanics and Molecular Dynamics Study

The enzyme SyrB2 employs an Fe^IV–oxo species to achieve selective C–H halogenation of l-threonine. Herein, we use combined quantum mechanical/molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations to decipher the mechanism of selective halogenation by SyrB2. Our QM/MM calculations show the presence of three Cl–Fe^IV–oxo isomers which interconvert, and only the one having its oxo ligand pointing toward the target C–H bond is active during the hydrogen atom abstraction (H-abstraction) process. The fate of the formed Cl–Fe^III–OH/R^• intermediate is determined by a hydrogen-bonding interaction between the Arg254 residue and the OH ligand of Cl–Fe^III–OH. The hydrogen bond not only prevents the OH group from participating in the followup rebound step to form a hydroxylated product but also facilitates the isomerization of the Cl–Fe^III–OH/R^• intermediate so that the Cl is directed toward the alkyl radical. The role of Arg254 in regulating the selectivity of chlorination is further discussed and connected to the experimentally observed effect of mutations of Arg247 (Arg247Glu and Arg247Ala) in the related CurA halogenase. The Ala118Asp and Ala118Glu mutants of SyrB2 were investigated by MD simulations, and they were found to suppress the H-bonding interaction of Arg254 with Cl–Fe^III–OH: this result is in accord with their experimentally observed suppressed chlorination activity. This novel mechanism highlights the role of the H-bonding interaction between the protein and a reaction intermediate

Highly Efficient CO₂ Electrolysis on Cathodes with Exsolved Alkaline Earth Oxide Nanostructures

The solid oxide CO₂ electrolyzer has the potential to provide storage solutions for intermittent renewable energy sources as well as to reduce greenhouse gas emissions. One of the key challenges remains the poor adsorption and activity toward CO₂ reduction on the electrolyzer cathode at typical operating conditions. Here, we show a novel approach in tailoring a perovskite titanate (La, Sr)­TiO_3+δ cathode surface, by the <i>in situ</i> growing of SrO nanoislands from the host material through the control of perovskite nonstoichiometry. These nanoislands provide very enhanced CO₂ adsorption and activation, with stability up to 800 °C, which is shown to be in an intermediate form between carbonate ions and molecular CO₂. The activation of adsorbed CO₂ molecules results from the interaction of exsolved SrO nanoislands and the defected titanate surface as revealed by DFT calculations. These cathode surface modifications result in an exceptionally high direct CO₂ electrolysis performance with current efficiencies near 100%

A Mononuclear Non-Heme High-Spin Iron(III)–Hydroperoxo Complex as an Active Oxidant in Sulfoxidation Reactions

We report the first direct experimental evidence showing that a high-spin iron­(III)–hydroperoxo complex bearing an N-methylated cyclam ligand can oxidize thioanisoles. DFT calculations showed that the reaction pathway involves heterolytic O–O bond cleavage and that the choice of the heterolytic pathway versus the homolytic pathway is dependent on the spin state and the number of electrons in the d_<i>xz</i> orbital of the Fe^III–OOH species

Integrating the g‑C₃N₄ Nanosheet with B–H Bonding Decorated Metal–Organic Framework for CO₂ Activation and Photoreduction

BIF-20, a zeolite-like porous boron imidazolate framework with high density of exposed B–H bonding, is combined with graphitic carbon nitride (g-C₃N₄) nanosheets <i>via</i> a facile electrostatic self-assembly approach under room temperature, forming an elegant composite BIF-20@g-C₃N₄ nanosheet. The as-constructed composite preferably captures CO₂ and further photoreduces CO₂ in high efficiency. The photogenerated excitations from the carbon nitride nanosheet can directionally migrate to B–H bonding, which effectively suppresses electron–hole pair recombination and thus greatly improves the photocatalytic ability. Compared to the g-C₃N₄ nanosheet, the BIF-20@g-C₃N₄ nanosheet composite displayed a much-enhanced photocatalytic CO₂ reduction activity, which is equal to 9.7-fold enhancements in the CH₄ evolution rate (15.524 μmol g^–1 h^–1) and 9.85-fold improvements in CO generation rate (53.869 μmol g^–1 h^–1). Density functional theory simulations further prove that the presence of B–H bonding in the composite is favorable for CO₂ adhesion and activation in the reaction process. Thus, we believe that the implantation of functional active sites into the porous matrix provides important insights for preparation of a highly efficient photocatalyst

Large Second-Harmonic Generation Responses Achieved by the Dimeric [Ge₂Se₄(μ-Se₂)]^4– Functional Motif in Polar Polyselenides A₄Ge₄Se₁₂ (A = Rb, Cs)

Two new polar polyselenides Rb₄Ge₄Se₁₂ (<b>1</b>) and Cs₄Ge₄Se₁₂ (<b>2</b>) with rarely reported dimeric [Ge₂Se₄(μ-Se₂)]^4– units were synthesized. They present large second-harmonic generation (SHG) intensities of 7.5 and 6.5 times that of the benchmark AgGaS₂ with type I phase-matching behavior, high laser-induced damaged thresholds, a wide transmission region and congruently melting behavior, making them excellent candidates for IR nonlinear optical (NLO) applications. The SHG functional motifs of both compounds are determined to be [Ge₂Se₄(μ-Se₂)]^4– unit by time-dependent density functional theory calculation, which further reveals that charge transfers from the lone pairs of terminal Se atoms to the five σ* orbitals of five-membered ring Ge₂Se₃ have a predominant contribution to the total SHG effect