A density functional study of O-O bond cleavage for a biomimetic non-heme iron complex demonstrating an Fe(v)-intermediate

Density functional theory using the B3LYP hybrid functional has been employed to investigate the reactivity of Fe(TPA) complexes (TPA = tris(2-pyridylmethyl)amine), which are known to catalyze stereospecific hydrocarbon oxidation when H(2)O(2) is used as oxidant. The reaction pathway leading to O-O bond heterolysis in the active catalytic species Fe(III)(TPA)-OOH has been explored, and it is shown that a high-valent iron-oxo intermediate is formed, where an Fe(V) oxidation state is attained, in agreement with previous suggestions based on experiments. In contrast to the analogous intermediate [(Por.)Fe(IV)=O](+1) in P450, the TPA ligand is not oxidized, and the electrons are extracted almost exclusively from the mononuclear iron center. The corresponding homolytic O-O bond cleavage, yielding the two oxidants Fe(IV)=O and the OH. radical, has also been considered, and it is shown that this pathway is inaccessible in the hydrocarbon oxidation reaction with Fe(TPA) and hydrogen peroxide. Investigations have also been performed for the O-O cleavage in the Fe(III)(TPA)-alkylperoxide species. In this case, the barrier for O-O homolysis is found to be slightly lower, leading to loss of stereospecificity and supporting the experimental conclusion that this is the preferred pathway for alkylperoxide oxidants. The difference between hydroperoxide and alkylperoxide as oxidant derives from the higher O-O bond strength for hydrogen peroxide (by 8.0 kcal/mol).     

Metal-bridging mechanism for O-O bond cleavage in cytochrome C oxidase

Density functional theory (B3LYP) has been applied to large models of the Fe(II)-Cu(I) binuclear center in cytochrome oxidase, investigating the mechanism of O-O bond cleavage in the mixed valence form of the enzyme. To comply with experimental information, the O(2) molecule is assumed to be bridging between iron and copper during the O-O bond cleavage, leading to the formation of a ferryl-oxo group and a cupric hydroxide. In accord with previous suggestions, the calculations show that it is energetically feasible to take the fourth electron needed in this reaction from the tyrosine residue that is cross-linked to one of the copper ligands, resulting in the formation of a neutral tyrosyl radical. However, the calculations indicate that simultaneous transfer of an electron and a proton from the tyrosine to dioxygen during bond cleavage leads to a barrier more than 10 kcal/mol higher than that experimentally determined. This may be overcome in two ways. If an extra proton in the binuclear center assists in the mechanism, the calculated reaction barrier agrees with experiment. Alternatively, the fourth electron might initially be supplied by a residue in the vicinity other than the tyrosine.     

Theoretical study of the mechanism of oxoiron(IV) formation from H2O2 and a nonheme iron(II) complex: O-O cleavage involving proton-coupled electron transfer

It has recently been shown that the nonheme oxoiron(IV) species supported by the 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane ligand (TMC) can be generated in near-quantitative yield by reacting [Fe(II)(TMC)(OTf)(2)] with a stoichiometric amount of H(2)O(2) in CH(3)CN in the presence of 2,6-lutidine (Li, F.; England, J.; Que, L., Jr. J. Am. Chem. Soc. 2010, 132, 2134-2135). This finding has major implications for O-O bond cleavage events in both Fenton chemistry and nonheme iron enzymes. To understand the mechanism of this process, especially the intimate details of the O-O bond cleavage step, a series of density functional theory (DFT) calculations and analyses have been carried out. Two distinct reaction paths (A and B) were identified. Path A consists of two principal steps: (1) coordination of H(2)O(2) to Fe(II) and (2) a combination of partial homolytic O-O bond cleavage and proton-coupled electron transfer (PCET). The latter combination renders the rate-limiting O-O cleavage effectively a heterolytic process. Path B proceeds via a simultaneous homolytic O-O bond cleavage of H(2)O(2) and Fe-O bond formation. This is followed by H abstraction from the resultant Fe(III)-OH species by an ?OH radical. Calculations suggest that path B is plausible in the absence of base. However, once 2,6-lutidine is added to the reacting system, the reaction barrier is lowered and more importantly the mechanistic path switches to path A, where 2,6-lutidine plays an essential role as an acid-base catalyst in a manner similar to how the distal histidine or glutamate residue assists in compound I formation in heme peroxidases. The reaction was found to proceed predominantly on the quintet spin state surface, and a transition to the triplet state, the experimentally known ground state for the TMC-oxoiron(IV) species, occurs in the last stage of the oxoiron(IV) formation process.     

Spectroscopic and kinetic studies of perturbed trinuclear copper clusters: the role of protons in reductive cleavage of the O-O bond in the multicopper oxidase Fet3p

The multicopper oxidase Fet3p couples four 1e(-) oxidations of substrate to the 4e(-) reduction of O2 to H2O. Fet3p uses four Cu atoms to accomplish this reaction: the type 1, type 2, and coupled binuclear type 3 sites. The type 2 and type 3 sites together form a trinuclear Cu cluster (TNC) which is the site of O2 reduction. This study focuses on mutants of two residues, E487 and D94, which lie in the second coordination sphere of the TNC and defines the role that each plays in the structural integrity of the TNC, its reactivity with O2, and in the directional movement of protons during reductive cleavage of the O-O bond. The E487D, E487A, and D94E mutants have been studied in the holo and type 1 depleted (T1D) forms. Residue E487, located near the T3 center, is found to be responsible for donation of a proton during the reductive cleavage of the O-O bond in the peroxide intermediate and an inverse kinetic solvent isotope effect, which indicates that this proton is already transferred when the O-O bond is cleaved. Residue D94, near the T2 site, plays a key role in the reaction of the reduced TNC with O2 and drives electron transfer from the T2 Cu to cleave the O-O bond by deprotonating the T2 Cu water ligand. A mechanism is developed where these second sphere residues participate in the proton assisted reductive cleavage of the O-O bond at the TNC.     

Heterolytic cleavage of peroxide by a diferrous compound generates metal-based intermediates identical to those observed with reactions utilizing oxygen-atom-donor molecules

Under cryogenic stopped-flow conditions, addition of 2-methyl-1-phenylprop-2-yl hydroperoxide (MPPH) to the diiron(II) compound, [Fe(2)(H(2)Hbamb)(2)(NMeIm)(2)] (1; NMeIm=N-methylimidazole; H(4)HBamb: 2,3-bis(2-hydroxybenzamido)dimethylbutane) results in heterolytic peroxide O-O bond cleavage, forming a high-valent species, 2. The UV/Vis spectrum of 2 and its kinetic behavior suggest parallel reactivity to that seen in the reaction of 1 with oxygen-atom-donor (OAD) molecules, which has been reported previously. Like the interaction with OAD molecules, the reaction of 1 with MPPH proceeds through a three step process, assigned to oxygen-atom transfer to the iron center to form a high-valent intermediate (2), ligand rearrangement of the metal complex, and, finally, decay to a diferric mu-oxo compound. Careful examination of the order of the reaction with MPPH reveals saturation behavior. This, coupled with the anomalous non-Arrhenius behavior of the first step of the reaction, indicates that there is a preequilibrium peroxide binding step prior to O-O bond cleavage. At higher temperatures, the addition of the base, proton sponge, results in a marked decrease in the rate of O-O bond cleavage to form 2; this is assigned as a peroxide deprotonation effect, indicating that the presence of protons is an important factor in the heterolytic cleavage of peroxide. This phenomenon has been observed in other iron-containing enzymes, the catalytic cycles of which include peroxide O-O bond cleavage.     

Proton-shuffle mechanism of O-O activation for formation of a high-valent oxo-iron species of bleomycin

Bleomycins (BLMs) can utilize H2O2 to cleave DNA in the presence of ferric ions. DFT calculations were used to study the mechanism of O-O bond cleavage in the low-spin FeIII-hydroperoxo complex of BLM. The following alternative hypotheses were investigated using realistic structural models: (a) heterolytic cleavage of the O-O bond, generating a Compound I (Cpd I) like intermediate, formally BLM-FeV=O; (b) homolytic O-O cleavage, leading to a BLM-FeIV=O species and an OH* radical; and (c) a direct O-O cleavage/H-abstraction mechanism by ABLM. The calculations showed that (a) is a facile and viable mechanism; it involves acid-base proton reshuffle mediated by the side-chain linkers of BLM, causing thereby heterolytic cleavage of the O-O bond and generation of Cpd I. Formation of Cpd I is found to involve a barrier of 13.3 kcal/mol, which is lower than the barriers in the alternative mechanisms (b and c) that possess respective barriers of 31 and 17 kcal/mol. The so-formed Cpd I species with a radical on the side-chain linker, methylvalerate (V), adjacent to the BLM-FeIV=O complex, resembles the formation of the active species of cytochrome c peroxidase in the Poulos-Kraut proton-shuffle mechanism in heme peroxidases (Poulos, T. L.; Kraut, J. J. Biol. Chem. 1980, 255, 8199-8205). Experimental data are discussed and shown to be in accord with this proposal. It suggests that the high-valence Cpd I species of BLM participates in the DNA cleavage. This is an alternative mechanistic hypothesis to the exclusive reactivity scenario based on ABLM (FeIII-OOH).     

Spectroscopic properties and electronic structure of low-spin Fe(III)-alkylperoxo complexes: homolytic cleavage of the O-O bond

The spectroscopic properties, electronic structure, and reactivity of the low-spin Fe(III)-alkylperoxo model complex [Fe(TPA)(OH(x))(OO(t)Bu)](x+) (1; TPA = tris(2-pyridylmethyl)amine, (t)Bu = tert-butyl, x = 1 or 2) are explored. The vibrational spectra of 1 show three peaks that are assigned to the O-O stretch (796 cm(-1)), the Fe-O stretch (696 cm(-)(1)), and a combined O-C-C/C-C-C bending mode (490 cm(-1)) that is mixed with upsilon(FeO). The corresponding force constants have been determined to be 2.92 mdyn/A for the O-O bond which is small and 3.53 mdyn/A for the Fe-O bond which is large. Complex 1 is characterized by a broad absorption band around 600 nm that is assigned to a charge-transfer (CT) transition from the alkylperoxo pi*(upsilon) to a t(2g) d orbital of Fe(III). This metal-ligand pi bond is probed by MCD and resonance Raman spectroscopies which show that the CT state is mixed with a ligand field state (t(2g) --> e(g)) by configuration interaction. This gives rise to two intense transitions under the broad 600 nm envelope with CT character which are manifested by a pseudo-A term in the MCD spectrum and by the shapes of the resonance Raman profiles of the 796, 696, and 490 cm(-1) vibrations. Additional contributions to the Fe-O bond arise from sigma interactions between mainly O-O bonding donor orbitals of the alkylperoxo ligand and an e(g) d orbital of Fe(III), which explains the observed O-O and Fe-O force constants. The observed homolytic cleavage of the O-O bond of 1 is explored with experimentally calibrated density functional (DFT) calculations. The O-O bond homolysis is found to be endothermic by only 15 to 20 kcal/mol due to the fact that the Fe(IV)=O species formed is highly stabilized (for spin states S = 1 and 2) by two strong pi and a strong sigma bond between Fe(IV) and the oxo ligand. This low endothermicity is compensated by the entropy gain upon splitting the O-O bond. In comparison, Cu(II)-alkylperoxo complexes studied before [Chen, P.; Fujisawa, K.; Solomon, E. I. J. Am. Chem. Soc. 2000, 122, 10177] are much less suited for O-O bond homolysis, because the resulting Cu(III)=O species is less stable. This difference in metal-oxo intermediate stability enables the O-O homolysis in the case of iron but directs the copper complex toward alternative reaction channels.     

Electronic structure and reactivity of low-spin Fe(III)-hydroperoxo complexes: comparison to activated bleomycin

The spectroscopic properties, electronic structure, and reactivity of the low-spin Fe(III)-hydroperoxo complex [Fe(N4Py)(OOH)](2+) (1, N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) are investigated in comparison to those of activated bleomycin (ABLM). Complex 1 is characterized by Raman features at 632 (Fe-O stretch) and 790 cm(-1) (O-O stretch), corresponding to a strong Fe-O bond (force constant 3.62 mdyn/A) and a weak O-O bond (3.05 mdyn/A). The UV-vis spectrum of 1 shows a broad absorption band around 550 nm that is assigned to a charge-transfer transition from the hydroperoxo to a t(2g) d orbital of Fe(III) using resonance Raman and MCD spectroscopies and density functional (DFT) calculations. Compared to low-spin [Fe(TPA)(OH(x))(OO(t)Bu)](x+)(TPA = tris(2-pyridylmethyl)amine, x = 1 or 2), an overall similar Fe-OOR bonding results for low-spin Fe(III)-alkylperoxo and -hydroperoxo species. Correspondingly, both systems show similar reactivities and undergo homolytic cleavage of the O-O bond. From the DFT calculations, this reaction is more endothermic for 1 due to the reduced stabilization of the .OH radical compared to .O(t)Bu and the absence of the hydroxo ligand that helps to stabilize the resulting Fe(IV)=O species. In contrast, ABLM has a somewhat different electronic structure where no pi donor bond between the hydroperoxo ligand and iron(III) is present [Neese, F.; Zaleski, J. M.; Loeb-Zaleski, K.; Solomon, E. I. J. Am. Chem. Soc. 2000, 122, 11703]. Possible reaction pathways for ABLM are discussed in relation to known experimental results.     

Targeted proton delivery in the catalyzed reduction of oxygen to water by bimetallic pacman porphyrins

A combined experimental and theoretical investigation of the role of proton delivery in determining O2 reduction pathways catalyzed by cofacial bisporphyrins is presented. A homologous family of dicobalt(II) Pacman porphyrins anchored by xanthene [Co2(DPX) (1) and Co2(DPXM) (3)] and dibenzofuran [Co2(DPD) (2) and Co2(DPDM) (4)] have been synthesized, characterized, and evaluated as catalysts for the direct four-proton, four-electron reduction of O2 to H2O. Structural analysis of the intramolecular diiron(III) mu-oxo complex Fe2O(DPXM) (5) and electrochemical measurements of 1-4 establish that Pacman derivatives bearing an aryl group trans to the spacer possess structural flexibilities and redox properties similar to those of their parent counterparts; however, these trans-aryl catalysts exhibit markedly reduced selectivities for the direct reduction of O2 to H2O over the two-proton, two-electron pathway to H2O2. Density functional theory calculations reveal that trans-aryl substitution results in inefficient proton delivery to O2-bound catalysts compared to unsubstituted congeners. In particular, the HOMO of [Co2(DPXM)(O2)]+ disfavors proton transfer to the bound oxygen species, funneling the O-O activation pathway to single-electron chemistry and the production of H2O2, whereas the HOMO of [Co2(DPX)(O2)]+ directs protonation to the [Co2O2] core to facilitate subsequent multielectron O-O bond activation to generate two molecules of H2O. Our findings highlight the importance of controlling both proton and electron inventories for specific O-O bond activation and offer a unified model for O-O bond activation within the clefts of bimetallic porphyrins.     

Electronic structure of high-spin iron(III)-alkylperoxo complexes and its relation to low-spin analogues: reaction coordinate of O-O bond homolysis.

The spectroscopic properties of the high-spin Fe(III)-alkylperoxo model complex [Fe(6-Me(3)TPA)(OH(x))(OO(t)Bu)](x)(+) (1; TPA = tris(2-pyridylmethyl)amine, (t)Bu = tert-butyl, x = 1 or 2) are defined and related to density functional calculations of corresponding models in order to determine the electronic structure and reactivity of this system. The Raman spectra of 1 show four peaks at 876, 842, 637, and 469 cm(-1) that are assigned with the help of normal coordinate analysis, and corresponding force constants have been determined to be 3.55 mdyn/A for the O-O and 2.87 mdyn/A for the Fe-O bond. Complex 1 has a broad absorption feature around 560 nm that is assigned to a charge-transfer (CT) transition from the alkylperoxo to a t(2g) d orbital of Fe(III) with the help of resonance Raman profiles and MCD spectroscopy. An additional contribution to the Fe-O bond arises from a sigma interaction between and an e(g) d orbital of iron. The electronic structure of 1 is compared to the related low-spin model complex [Fe(TPA)(OH(x))(OO(t)Bu)](x)(+) and the reaction coordinate for O-O homolysis is explored for both the low-spin and the high-spin Fe(III)-alkylperoxo systems. Importantly, there is a barrier for homolytic cleavage of the O-O bond on the high-spin potential energy surface that is not present for the low-spin complex, which is therefore nicely set up for O-O homolysis. This is reflected by the electronic structure of the low-spin complex having a strong Fe-O and a weak O-O bond due to a strong Fe-O sigma interaction. In addition, the reaction coordinate of the Fe-O homolysis has been investigated, which is a possible decay pathway for the high-spin system, but which is thermodynamically unfavorable for the low-spin complex.     

Characterization of a high-spin non-heme Fe(III)-OOH intermediate and its quantitative conversion to an Fe(IV)═O complex

We have generated a high-spin Fe(III)-OOH complex supported by tetramethylcyclam via protonation of its conjugate base and characterized it in detail using various spectroscopic methods. This Fe(III)-OOH species can be converted quantitatively to an Fe(IV)═O complex via O-O bond cleavage; this is the first example of such a conversion. This conversion is promoted by two factors: the strong Fe(III)-OOH bond, which inhibits Fe-O bond lysis, and the addition of protons, which facilitates O-O bond cleavage. This example provides a synthetic precedent for how O-O bond cleavage of high-spin Fe(III)-peroxo intermediates of non-heme iron enzymes may be promoted.     

QM/MM study of mechanisms for compound I formation in the catalytic cycle of cytochrome P450cam

In the catalytic cycle of cytochrome P450cam, after molecular oxygen binds as a ligand to the heme iron atom to yield a ferrous dioxygen complex, there are fast proton transfers that lead to the formation of the active species, Compound I (Cpd I), which are not well understood because they occur so rapidly. In the present work, the conversion of the ferric hydroperoxo complex (Cpd 0) to Cpd I has been investigated by combined quantum-mechanical/molecular-mechanical (QM/MM) calculations. The residues Asp(251) and Glu(366) are considered as proton sources. In mechanism I, a proton is transported to the distal oxygen atom of the hydroperoxo group via a hydrogen bonding network to form protonated Cpd 0 (prot-Cpd0: FeOOH(2)), followed by heterolytic O-O bond cleavage that generates Cpd I and water. Although a local minimum is found for prot-Cpd0 in the Glu(366) channel, it is very high in energy (more than 20 kcal/mol above Cpd 0) and the barriers for its decay are only 3-4 kcal/mol (both toward Cpd 0 and Cpd I). In mechanism II, an initial O-O bond cleavage followed by a concomitant proton and electron transfer yields Cpd I and water. The rate-limiting step in mechanism II is O-O cleavage with a barrier of about 13-14 kcal/mol. According to the QM/MM calculations, the favored low-energy pathway to Cpd I is provided by mechanism II in the Asp(251) channel. Cpd 0 and Cpd I are of similar energies, with a slight preference for Cpd I.     

Chemoselective alkane oxidation by superoxo-vanadium(V) in vanadosilicate molecular sieves

Electron paramagnetic resonance (EPR) spectroscopy of reactive superoxo-vanadium(V) species in vanadosilicate molecular sieves (microporous VS-1 and mesoporous V-MCM-41) generated on contact with H2O2, tert-butyl hydroperoxide (TBHP), or (H2+O2) is reported for the first time. By suitable choice of the silicate structure, solvent, and oxidant, we could control the vanadium-(O2-*) bond (i.e., the V-O bond) covalency, the mode of O-O cleavage (in the superoxo species), and, therefore, chemoselectivity in the oxidation of n-hexane: Oxidation by TBHP over V-MCM-41, for example, yielded 27.2% of (n-hexanol+n-hexanal+n-hexanoic acid), among the highest chemoselectivities for oxidation of the terminal -CH3 in a linear paraffin reported to date. Over these vanadosilicates, oxidation of the primary C-H bond occurs only via a homolytic O-O bond cleavage; the secondary C-H bond oxidations may proceed via both the homo- and heterolytic O-O cleavage mechanisms.     

Density functional theory study on a missing piece in understanding of heme chemistry: the reaction mechanism for indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme-containing dioxygenases and catalyze oxidative cleavage of the pyrrole ring of L-tryptophan. On the basis of three recent crystal structures of these heme-containing dioxygenases, two new mechanistic pathways were proposed by several groups. Both pathways start with electrophilic addition of the Fe(II)-bound dioxygen concerted with proton transfer (oxygen ene-type reaction), followed by either formation of a dioxetane intermediate or Criegee-type rearrangement. However, density functional theory (DFT) calculations do not support the proposed concerted oxygen ene-type and Criegee-type rearrangement pathways. On the basis of DFT calculations, we propose a new mechanism for dioxygen activation in these heme systems. The mechanism involves (a) direct electrophilic addition of the Fe(II)-bound oxygen to the C2 or C3 position of the indole in a closed-shell singlet state or (b) direct radical addition of the Fe(III)-superoxide to the C2 position of the indole in a triplet (or open-shell singlet) state. Then, a radical-recombination or nearly barrierless charge-recombination step from the resultant diradical or zwitterionic intermediates, respectively, proceeds to afford metastable dioxetane intermediates, followed by ring-opening of the dioxetanes. Alternatively, homolytic O-O bond cleavage from the diradical intermediate followed by oxo attack and facile C2-C3 bond cleavage could compete with the dioxetane formation pathway. Effects of ionization of the imidazole and negatively charged oxyporphyrin complex on the key dioxygen activation process are also studied.     

The Poulos-Kraut mechanism of Compound I formation in horseradish peroxidase: a QM/MM study

QM/MM calculations are used to elucidate the Poulos-Kraut (Poulos, T. L.; Kraut, J. J. Biol. Chem. 1980, 255, 8199-8205) mechanism of O-O bond activation and Compound I (Cpd I) formation in HRP, in conditions corresponding to neutral to basic pH. Attempts to generate Compound I directly from the Fe(H2O2) complex by migrating the proton from the proximal oxygen to the distal one (1,2- proton shift) result in high barriers. The lowest energy mechanism was found to involve initial deprotonation of ferric hydrogen peroxide complex (involving spin crossover from the quartet to the doublet state) by His42 to form ferric-hydroperoxide (Cpd 0). Subsequently, the distal OH group of Cpd 0 is pulled by Arg38 and reprotonated by His42(H+) to form Cpd I and a water molecule that bridges the two residues. The structures of the intermediate and the transition state reveal the manner by which the Arg-His residues promote cooperatively the electronic reorganization that is required to attend the heterolytic O-O cleavage.     

Axial ligand and spin-state influence on the formation and reactivity of hydroperoxo-iron(III) porphyrin complexes

The present study focuses on the formation and reactivity of hydroperoxo-iron(III) porphyrin complexes formed in the [Fe(III)(tpfpp)X]/H(2)O(2)/HOO(-) system (TPFPP=5,10,15,20-tetrakis(pentafluorophenyl)-21H,23H-porphyrin; X=Cl(-) or CF(3) SO(3)(-)) in acetonitrile under basic conditions at -15 °C. Depending on the selected reaction conditions and the active form of the catalyst, the formation of high-spin [Fe(III)(tpfpp)(OOH)] and low-spin [Fe(III)(tpfpp)(OH)(OOH)] could be observed with the application of a low-temperature rapid-scan UV/Vis spectroscopic technique. Axial ligation and the spin state of the iron(III) center control the mode of O-O bond cleavage in the corresponding hydroperoxo porphyrin species. A mechanistic changeover from homo- to heterolytic O-O bond cleavage is observed for high- [Fe(III)(tpfpp)(OOH)] and low-spin [Fe(III)(tpfpp)(OH)(OOH)] complexes, respectively. In contrast to other iron(III) hydroperoxo complexes with electron-rich porphyrin ligands, electron-deficient [Fe(III)(tpfpp)(OH)(OOH)] was stable under relatively mild conditions and could therefore be investigated directly in the oxygenation reactions of selected organic substrates. The very low reactivity of [Fe(III)(tpfpp)(OH)(OOH)] towards organic substrates implied that the ferric hydroperoxo intermediate must be a very sluggish oxidant compared with the iron(IV)-oxo porphyrin π-cation radical intermediate in the catalytic oxygenation reactions of cytochrome P450.     

Does the decomposition of peroxydicarbonates and diacyl peroxides proceed in a stepwise or concerted pathway?

M?ller-Plesset perturbation theory and density functional theory calculations are used to study decomposition mechanisms of polymerization initiators, such as diethyl peroxydicarbonate, trifluoroacetyl peroxide, and acetyl peroxide, which possess a general structure of RC(O)OO(O)CR. It is found that the decomposition of initiators with electron-donating R groups follows two favorable stepwise pathways: a two-bond cleavage mechanism in which the O-O single bond and one of R-C bonds of [R-C(O)O-O(O)C-R] break simultaneously followed by decomposition of the R-C(O)O(*) radical and a one-bond cleavage mechanism in which the single O-O bond cleavage produces a carboxyl radical pair and a subsequent decomposition of the carboxyl radicals. It is also found that the initiators with electron-withdrawing R groups follow the two-bond cleavage pathway only. Geometrical and energetic analyses indicate that despite the similar structures of the peroxydicarbonates, quite different decomposition energy barriers are determined by the nature of the R groups.     

Multiple active intermediates in oxidation reaction catalyzed by synthetic heme-thiolate complex relevant to cytochrome p450

We have studied oxidation reactions using a synthetic heme-thiolate (SR complex) in order to ascertain the contributions of multiple intermediates derived from heme-thiolate to the oxygen atom transfer reaction to substrate. First, degradation of peroxyphenylacetic acid (PPAA) was examined in the presence of various substrates. The O-O bond cleavage mode of PPAA was clearly dependent on the reactivity of the substrate, and an easily oxidizable substrate enhanced heterolytic O-O bond cleavage. Second, competitive oxidations of cyclooctane and cyclooctene were carried out with various peroxybenzoic acids containing a series of substituents at the para-position as an oxygen source. The ratios of alkane hydroxylation rate/alkene epoxidation rate were dependent on the nature of the para-substituent of the oxidant. We conclude that substrate and oxidant interact with each other during the oxygen atom transfer reaction, that is, oxidation reaction occurs before O-O bond cleavage, even in the reaction catalyzed by heme-thiolate, which is considered to promote O-O bond cleavage. The results of an (18)O-incorporation study that is frequently performed to determine the active intermediates derived from iron porphyrins were consistent with this conclusion.     

On the extent of intramolecular hydrogen bonding in gas-phase and hydrated 1,2-ethanediol

We investigate the quantum dynamical nature of hydrogen bonding in 1,2-ethanediol and monohydrated 1,2-ethanediol using different levels of ab initio theory. Global full-dimensional potential energy surfaces were constructed from PW91/cc-pVDZ, B3LYP/cc-pVDZ, and MP2/cc-pVDZ ab initio data for gas-phase and monohydrated 1,2-ethanediol, using a modified Shepard interpolation scheme. Zero-point energies and nuclear vibrational wave functions were calculated on these surfaces using the quantum diffusion Monte Carlo algorithm. The nature of intra- and intermolecular hydrogen bonding in these molecules was investigated by considering a ground-state nuclear vibrational wavefunction with reduced complete nuclear permutation and inversion (CNPI) symmetry. Separate wavefunction histograms were determined from the ground-state nuclear vibrational wavefunction by projection into bondlength coordinates. The O-H and O-O wavefunction histograms and vibrationally averaged distances were then used to probe the extent of intra- and intermolecular hydrogen bonding. From these data, we conclude that gas-phase ethanediol may possess a weak hydrogen bond, with a relatively short O-O distance but no detectable proton delocalization. Monohydrated ethanediol was found to exhibit no intramolecular hydrogen bonding but instead possessed two intermolecular hydrogen bonds, indicated by both shortening of the O-O distance and significant proton delocalization. The degree of proton delocalization and shortening of the vibrationally averaged O-O distance was found to be dependent on the ab initio method used to generate the potential energy surface (PES) data set.     

Cooperative pull and push effects on the O-O bond cleavage in acylperoxo complexes of [(Salen)MnIIIL]: ensuring formation of manganese(V) oxo species

The acidity (pull) and the axial ligand (push) effects on the O-O bond cleavage in the [(Salen)Mn(III)(RCO(3))L] acylperoxo complexes, with model L = none, NH(3), and HCO(2)(-) (1), have been studied with B3LYP density functional calculations. The acidic conditions have been mimicked by explicit protonation of 1 to afford a variety of [(Salen)Mn(III)(RCO(3)H)L] (2) and [(SalenH)Mn(III)(RCO(3))L] (3) complexes in ground quintet states. The protonation assists the O-O bond heterolysis, thus primarily forming highly reactive Mn(V)(O) species, and consequently suppresses formation of the less reactive Mn(IV)(O) species through homolytic channel described earlier in 1 [Khavrutskii, I. V.; Rahim, R. R.; Musaev, D. G.; Morokuma, K. J. Phys. Chem. B 2004, 108, 3845-3854]. In addition to the qualitative change of the O-O bond cleavage mode, the protonation affects the rate of the O-O bond cleavage. Therefore, varying the acidity of the reaction media helps control the O-O bond cleavage mode and rate.