Kyung-Bin Cho

A Highly Reactive Mononuclear Non-Heme Manganese(IV)–Oxo Complex That Can Activate the Strong C–H Bonds of Alkanes

A mononuclear non-heme manganese(IV)-oxo complex has been synthesized and characterized using various spectroscopic methods. The Mn(IV)-oxo complex shows high reactivity in oxidation reactions, such as C-H bond activation, oxidations of olefins, alcohols, sulfides, and aromatic compounds, and N-dealkylation. In C-H bond activation, the Mn(IV)-oxo complex can activate C-H bonds as strong as those in cyclohexane. It is proposed that C-H bond activation by the non-heme Mn(IV)-oxo complex does not occur via an oxygen-rebound mechanism. The electrophilic character of the non-heme Mn(IV)-oxo complex is demonstrated by a large negative ρ value of -4.4 in the oxidation of para-substituted thioanisoles.

A Mononuclear Non-Heme Manganese(IV)−Oxo Complex Binding Redox-Inactive Metal Ions

Redox-inactive metal ions play pivotal roles in regulating the reactivities of high-valent metal-oxo species in a variety of enzymatic and chemical reactions. A mononuclear non-heme Mn(IV)-oxo complex bearing a pentadentate N5 ligand has been synthesized and used in the synthesis of a Mn(IV)-oxo complex binding scandium ions. The Mn(IV)-oxo complexes were characterized with various spectroscopic methods. The reactivities of the Mn(IV)-oxo complex are markedly influenced by binding of Sc(3+) ions in oxidation reactions, such as a ~2200-fold increase in the rate of oxidation of thioanisole (i.e., oxygen atom transfer) but a ~180-fold decrease in the rate of C-H bond activation of 1,4-cyclohexadiene (i.e., hydrogen atom transfer). The present results provide the first example of a non-heme Mn(IV)-oxo complex binding redox-inactive metal ions that shows a contrasting effect of the redox-inactive metal ions on the reactivities of metal-oxo species in the oxygen atom transfer and hydrogen atom transfer reactions.

A mononuclear nonheme iron(IV)-oxo complex which is more reactive than cytochrome P450 model compound I

A highly reactive mononuclear nonheme iron(IV)-oxo complex with a low-spin (S = 1) triplet ground state in both C–H bond activation and oxo transfer reactions is reported; this nonheme iron(IV)-oxo complex is more reactive than an iron(IV)-oxo porphyrin π-cation radical (i.e., a model of cytochrome P450 compound I) and is the most reactive species in kinetic studies among nonheme iron(IV)-oxo complexes reported so far. DFT calculations support the experimental results with extremely low activation barriers in the C–H bond activation of cyclohexane and 1,4-cyclohexadiene. The DFT calculations reveal that the S = 1 state is set up to easily lead to the highly reactive S = 2 high-spin iron(IV)-oxo species.

Ligand topology effect on the reactivity of a mononuclear nonheme iron(IV)-oxo complex in oxygenation reactions.

Mononuclear nonheme iron(IV)-oxo complexes with two different topologies, cis-α-[Fe(IV)(O)(BQCN)](2+) and cis-β-[Fe(IV)(O)(BQCN)](2+), were synthesized and characterized with various spectroscopic methods. The effect of ligand topology on the reactivities of nonheme iron(IV)-oxo complexes was investigated in C-H bond activation and oxygen atom-transfer reactions; cis-α-[Fe(IV)(O)(BQCN)](2+) was more reactive than cis-β-[Fe(IV)(O)(BQCN)](2+) in the oxidation reactions. The reactivity difference between the cis-α and cis-β isomers of [Fe(IV)(O)(BQCN)](2+) was rationalized with the Fe(IV/III) redox potentials of the iron(IV)-oxo complexes: the Fe(IV/III) redox potential of the cis-α isomer was 0.11 V higher than that of the cis-β isomer.

Water as an Oxygen Source: Synthesis, Characterization, and Reactivity Studies of a Mononuclear Nonheme Manganese(IV) Oxo Complex†

High-valent manganese oxo species have been invoked as key intermediates in the oxidation of organic substrates by heme and nonheme manganese catalysts, and in water oxidation by the oxygen-evolving complex (OEC) in photosystem II (PS II). To elucidate the chemical and physical properties of high-valent manganese oxo intermediates, a number of heme and nonheme Mn and Mn oxo complexes have been synthesized, and characterized by using various spectroscopic methods and X-ray crystallography. The reactivities of these species have also been investigated in oxidation reactions, such as C H bond activation, olefin epoxidation, halogenation, and hydrideand electron-transfer reactions. In PS II, the oxidation of water by the OEC induces the generation of high-valent Mn oxo species by a protoncoupled electron transfer (PCET) mechanism. The oxygen atom in the Mn oxo intermediate is derived from water. Biomimetic studies have established the formation of ruthenium oxo complexes in water oxidation in the presence of a strong oxidant, such as Ce or [Ru(bpy)3] 3+ (bpy = 2,2 bipyridine). Very recently, we have generated mononuclear nonheme Fe oxo complexes using water as an oxygen source and Ce as an one-electron oxidant. Since it has been proposed that high-valent manganese oxo species are generated by the oxidation of water at the OEC of PS II, we attempted to generate high-valent manganese oxo species in a similar fashion. Herein, we report the generation of a mononuclear nonheme Mn oxo complex using water as an oxygen source and Ce as an one-electron oxidant. The spectroscopic characterization and DFT-optimized structure of the intermediate are also reported. We also report the reactivity of the nonheme Mn oxo complex in oxygenation reactions. Addition of cerium(IV) ammonium nitrate (CAN; 8 mm) to a reaction solution containing [Mn(BQCN)](CF3SO3)2 (1; 2 mm ; BQCN = N,N’-dimethyl-N,N’-bis(8-quinolyl)cyclohexanediamine; see the crystal structure of 1 in Figure 1 and

Oxidation of tertiary amines by cytochrome p450-kinetic isotope effect as a spin-state reactivity probe.

Two types of tertiary amine oxidation processes, namely, N-dealkylation and N-oxygenation, by compound I (Cpd I) of cytochrome P450 are studied theoretically using hybrid DFT calculations. All the calculations show that both N-dealkylation and N-oxygenation of trimethylamine (TMA) proceed preferentially from the low-spin (LS) state of Cpd I. Indeed, the computed kinetic isotope effects (KIEs) for the rate-controlling hydrogen abstraction step of dealkylation show that only the KIE(LS) fits the experimental datum, whereas the corresponding value for the high-spin (HS) process is much higher. These results second those published before for N,N-dimethylaniline (DMA), and as such, they further confirm the conclusion drawn then that KIEs can be a sensitive probe of spin state reactivity. The ferric-carbinolamine of TMA decomposes most likely in a non-enzymatic reaction since the Fe-O bond dissociation energy (BDE) is negative. The computational results reveal that in the reverse reaction of N-oxygenation, the N-oxide of aromatic amine can serve as a better oxygen donor than that of aliphatic amine to generate Cpd I. This capability of the N-oxo derivatives of aromatic amines to transfer oxygen to the heme, and thereby generate Cpd I, is in good accord with experimental data previously reported.

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(xz) orbital of the Fe(III)-OOH species.

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. J. Am. Chem. Soc.2010, 132, 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 (S = 5/2) or intermediate-spin (S = 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. Nat. Chem.2011, 3, 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 S = 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+).

Interplay of Experiment and Theory in Elucidating Mechanisms of Oxidation Reactions by a Nonheme RuIVO Complex

A comprehensive experimental and theoretical study of the reactivity patterns and reaction mechanisms in alkane hydroxylation, olefin epoxidation, cyclohexene oxidation, and sulfoxidation reactions by a mononuclear nonheme ruthenium(IV)-oxo complex, [Ru(IV)(O)(terpy)(bpm)](2+) (1), has been conducted. In alkane hydroxylation (i.e., oxygen rebound vs oxygen non-rebound mechanisms), both the experimental and theoretical results show that the substrate radical formed via a rate-determining H atom abstraction of alkanes by 1 prefers dissociation over oxygen rebound and desaturation processes. In the oxidation of olefins by 1, the observations of a kinetic isotope effect (KIE) value of 1 and styrene oxide formation lead us to conclude that an epoxidation reaction via oxygen atom transfer (OAT) from the Ru(IV)O complex to the C═C double bond is the dominant pathway. Density functional theory (DFT) calculations show that the epoxidation reaction is a two-step, two-spin-state process. In contrast, the oxidation of cyclohexene by 1 affords products derived from allylic C-H bond oxidation, with a high KIE value of 38(3). The preference for H atom abstraction over C═C double bond epoxidation in the oxidation of cyclohexene by 1 is elucidated by DFT calculations, which show that the energy barrier for C-H activation is 4.5 kcal mol(-1) lower than the energy barrier for epoxidation. In the oxidation of sulfides, sulfoxidation by the electrophilic Ru-oxo group of 1 occurs via a direct OAT mechanism, and DFT calculations show that this is a two-spin-state reaction in which the transition state is the lowest in the S = 0 state.

Determination of Spin Inversion Probability, H-Tunneling Correction, and Regioselectivity in the Two-State Reactivity of Nonheme Iron(IV)-Oxo Complexes

We show by experiments that nonheme Fe(IV)O species react with cyclohexene to yield selective hydrogen atom transfer (HAT) reactions with virtually no C═C epoxidation. Straightforward DFT calculations reveal, however, that C═C epoxidation on the S = 2 state possesses a low-energy barrier and should contribute substantially to the oxidation of cyclohexene by the nonheme Fe(IV)O species. By modeling the selectivity of this two-site reactivity, we show that an interplay of tunneling and spin inversion probability (SIP) reverses the apparent barriers and prefers exclusive S = 1 HAT over mixed HAT and C═C epoxidation on S = 2. The model enables us to derive a SIP value by combining experimental and theoretical results.