Theoretical Investigations into C–H Bond Activation Reaction by Nonheme Mn^IVO Complexes: Multistate Reactivity with No Oxygen Rebound

Recently published experimental results on a nonheme synthetic [(Bn-TPEN)­Mn^IVO]²⁺ complex reveal that it is capable of activating strong C–H bonds. However, the final products are shown to contain Mn^III instead of the expected Mn^II, which should be formed if a rebound mechanism similar to what is assumed for heme Fe^IVO was to occur. It was proposed that the substrate radical generated during H-abstraction dissociates from the Mn^IIIOH complex and undergoes an additional reaction to a second molecule of Mn^IVO, leading to Mn^III. Density functional calculations reveal the root cause of why a follow-up rebound to form Mn^II and alcohol is not preferred in this system. It is further shown that nonheme Mn^IVO has a more complex spin-state manifold during C–H activation reactions compared with Fe^IVO, and that spin-state matters in oxidative chemistry of metal-oxo reagents

Investigating Superoxide Transfer through a μ‑1,2‑O₂ Bridge between Nonheme Ni^III–Peroxo and Mn^II Species by DFT Methods to Bridge Theoretical and Experimental Views

Previously, a fast unprecedented O₂^•– transfer reaction has been observed experimentally when adding a Mn^II complex into a solution containing a Ni^III–peroxo complex. Due to the fast reaction rate, no intermediates were observed. We have investigated this reaction with density functional theory (DFT) and show that DFT is unusually problematic in reproducing the correct spin state for the investigated Ni^III–peroxo complex, something which calls for examination of all previous Ni–dioxygen studies. Surprisingly, the BP86 functional is shown to yield energies more in agreement with known experiments than B3LYP. The calculations reveal for the first time an intermediate structure in a complete O₂^•– transfer reaction, shown here to be a short-lived bridging Ni-(μ-1,2-O₂)-Mn structure

External Electric Field Can Control the Catalytic Cycle of Cytochrome P450_cam: A QM/MM Study

This Letter presents a systematic study of effects of external electric fields (EEFs) on the key species and steps in the catalytic cycle of cytochrome P450_cam. The QM/MM/EEF results demonstrate that an EEF can exert significant effects on the entire catalytic cycle of P450. The EEF will control the initial gating of the cycle, its rate-determining step, its O₂ uptake, the geometry of its resting state, and the spin-state ordering and electronic structure of its various active species. Furthermore, the EEF has a potential of controlling the bond activation reactions of the active species as well. These effects are pronounced when the EEF is aligned perpendicular to the porphyrin plane

Reactions of a Chromium(III)-Superoxo Complex and Nitric Oxide That Lead to the Formation of Chromium(IV)-Oxo and Chromium(III)-Nitrito Complexes

The reaction of an end-on Cr­(III)-superoxo complex bearing a 14-membered tetraazamacrocyclic TMC ligand, [Cr^III(14-TMC)­(O₂)­(Cl)]⁺, with nitric oxide (NO) resulted in the generation of a stable Cr­(IV)-oxo species, [Cr^IV(14-TMC)­(O)­(Cl)]⁺, via the formation of a Cr­(III)-peroxynitrite intermediate and homolytic O–O bond cleavage of the peroxynitrite ligand. Evidence for the latter comes from electron paramagnetic resonance spectroscopy, computational chemistry and the observation of phenol nitration chemistry. The Cr­(IV)-oxo complex does not react with nitrogen dioxide (NO₂), but reacts with NO to afford a Cr­(III)-nitrito complex, [Cr^III(14-TMC)­(NO₂)­(Cl)]⁺. The Cr­(IV)-oxo and Cr­(III)-nitrito complexes were also characterized spectroscopically and/or structurally

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

Dioxygen Activation by a Non-Heme Iron(II) Complex: Theoretical Study toward Understanding Ferric–Superoxo Complexes

We present a systematic study using density functional theory (DFT) and coupled cluster (CCSD­(T)) computations with an aim of characterizing a non-heme ferric–superoxo complex [(TMC)­Fe­(O₂)]²⁺ (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) that was proposed to perform allylic C–H activation of cyclohexene (Lee, Y.-M. et al. <i>J. Am. Chem. Soc.</i> <b>2010</b>, <i>132</i>, 10668). As such, we investigated a series of iron–O₂ species without and with a sixth ligand bound to the iron ion in different O₂ coordination modes (end-on and side-on) and different spin states. Most of the iron–O₂ complexes were found to be iron­(III)–superoxo species, Fe­(III)­(O₂^–), with high-spin (<i>S</i> = 5/2) or intermediate-spin (<i>S</i> = 3/2) ferric centers coupled ferromagnetically or antiferromagnetically to the superoxide anion radical. One iron­(IV)–peroxo state, Fe­(IV)­(O₂^2–), was also examined. The preference for ferromagnetic or antiferromagnetic coupling modes between the superoxo and ferric radicals was found to depend on the FeOO angle, where a side-on tilt favors ferromagnetic coupling whereas the end-on tilt favors antiferromagnetic states. Experimental findings, e.g., the effects of solvent, spin state, and redox potential of non-heme Fe­(II) complexes on O₂ activation, were corroborated in this work. Solvent effects were found to disfavor O₂ binding, relative to the unbound ferrous ion and O₂. The potential H-abstraction reactivity of the iron­(III)–superoxo species was considered in light of the recently proposed exchange-enhanced reactivity principle (Shaik, S.; Chen, H.; Janardanan, D. <i>Nat. Chem.</i> <b>2011</b>, <i>3</i>, 19). It is concluded that localization and/or decoupling of an unpaired electron in the d-block of high-spin Fe­(III) center in the <i>S</i> = 2 and 3 ferric–superoxo complexes during H abstractions enhances exchange stabilization and may be the root cause of the observed reactivity of [(TMC)­Fe­(O₂)]²⁺

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

Factors Controlling the Chemoselectivity in the Oxidation of Olefins by Nonheme Manganese(IV)-Oxo Complexes

We report the oxidation of cyclic olefins, such as cyclohexene, cyclohexene-<i>d</i>₁₀, and cyclooctene, by mononuclear nonheme manganese­(IV)-oxo (Mn^IVO) and triflic acid (HOTf)-bound Mn^IVO complexes. In the oxidation of cyclohexene, the Mn^IVO complexes prefer the CH bond activation to the CC double bond epoxidation, whereas the CC double bond epoxidation becomes a preferred reaction pathway in the cyclohexene oxidation by HOTf-bound Mn^IVO complexes. In contrast, the oxidation of cyclohexene-<i>d</i>₁₀ and cyclooctene by the Mn^IVO complexes occurs predominantly via the CC double bond epoxidation. This conclusion is drawn from the product analysis and kinetic studies of the olefin oxidation reactions, such as the epoxide versus allylic oxidation products, the formation of Mn­(II) versus Mn­(III) products, and the kinetic analyses. Overall, the experimental results suggest that the energy barrier of the CC double bond epoxidation is very close to that of the allylic CH bond activation in the oxidation of cyclic olefins by high-valent metal-oxo complexes. Thus, the preference of the reaction pathways is subject to changes upon small manipulation of the reaction environments, such as the supporting ligands and metal ions in metal-oxo species, the presence of HOTf (i.e., HOTf-bound Mn^IVO species), and the allylic CH­(D) bond dissociation energies of olefins. This is confirmed by DFT calculations in the oxidation of cyclohexene and cyclooctene, which show multiple pathways with similar rate-limiting energy barriers and depending on the allylic CH bond dissociation energies. In addition, the possibility of excited state reactivity in the current system is confirmed for epoxidation reactions

Mechanistic Insights into the C–H Bond Activation of Hydrocarbons by Chromium(IV) Oxo and Chromium(III) Superoxo Complexes

The mechanism of the C–H bond activation of hydrocarbons by a nonheme chromium­(IV) oxo complex bearing an N-methylated tetraazamacrocyclic cyclam (TMC) ligand, [Cr^IV(O)­(TMC)­(Cl)]⁺ (<b>2</b>), has been investigated experimentally and theoretically. In experimental studies, reaction rates of <b>2</b> with substrates having weak C–H bonds were found to depend on the concentration and bond dissociation energies of the substrates. A large kinetic isotope effect value of 60 was determined in the oxidation of dihydroanthracene (DHA) and deuterated DHA by <b>2</b>. These results led us to propose that the C–H bond activation reaction occurs via a H-atom abstraction mechanism, in which H-atom abstraction of substrates by <b>2</b> is the rate-determining step. In addition, formation of a chromium­(III) hydroxo complex, [Cr^III(OH)­(TMC)­(Cl)]⁺ (<b>3</b>), was observed as a decomposed product of <b>2</b> in the C–H bond activation reaction. The Cr^IIIOH product was characterized unambiguously with various spectroscopic methods and X-ray crystallography. Density functional theory (DFT) calculations support the experimental observations that the C–H bond activation by <b>2</b> does not occur via the conventional H-atom-abstraction/oxygen-rebound mechanism and that <b>3</b> is the product formed in this C–H bond activation reaction. DFT calculations also propose that <b>2</b> may have some Cr^IIIO^•– character. The oxidizing power of <b>2</b> was then compared with that of a chromium­(III) superoxo complex bearing the identical TMC ligand, [Cr^III(O₂)­(TMC)­(Cl)]⁺ (<b>1</b>), in the C–H bond activation reaction. By performing reactions of <b>1</b> and <b>2</b> with substrates under identical conditions, we were able to demonstrate that the reactivity of <b>2</b> is slightly greater than that of <b>1</b>. DFT calculations again support this experimental observation, showing that the rate-limiting barrier for the reaction with <b>2</b> is slightly lower than that of <b>1</b>

Evidence for an Alternative to the Oxygen Rebound Mechanism in C–H Bond Activation by Non-Heme Fe^IVO Complexes

The hydroxylation of alkanes by heme Fe^IVO species occurs via the hydrogen abstraction/oxygen rebound mechanism. It has been assumed that non-heme Fe^IVO species follow the heme Fe^IVO paradigm in C–H bond activation reactions. Herein we report theoretical and experimental evidence that C–H bond activation of alkanes by synthetic non-heme Fe^IVO complexes follows an alternative mechanism. Theoretical calculations predicted that dissociation of the substrate radical formed via hydrogen abstraction from the alkane is more favorable than the oxygen rebound and desaturation processes. This theoretical prediction was verified by experimental results obtained by analyzing iron and organic products formed in the C–H bond activation of substrates by non-heme Fe^IVO complexes. The difference in the behaviors of heme and non-heme Fe^IVO species is ascribed to differences in structural preference and exchange-enhanced reactivity. Thus, the general consensus that C–H bond activation by high-valent metal–oxo species, including non-heme Fe^IVO, occurs via the conventional hydrogen abstraction/oxygen rebound mechanism should be viewed with caution