Dioxygen activation at monovalent nickel

The monovalent oxidation state of nickel has received a growing amount of attention in recent years, in part due to its suggested catalytic role in a number of metalloprotein-mediated transformations. In coordination chemistry, nickel(I) is suitable for reductive activation of dioxygen, provided ligands are used that stabilize this less common oxidation state against disproportionation reactions. Two distinct molecular systems have been explored, which have provided access to new nickel-dioxygen structure types, namely, monomeric side-on and end-on superoxo and trans-micro-1,2-peroxo-dinickel complexes. The geometric and electronic structures of the complexes have been established by advanced spectroscopic methods, including resonance Raman and X-ray absorption spectroscopies, and augmented by density functional theory analyses.     

High-valent iron(IV)-oxo complexes of heme and non-heme ligands in oxygenation reactions

High-valent iron(IV)-oxo species have been implicated as the key reactive intermediates in the catalytic cycles of dioxygen activation by heme and non-heme iron enzymes. Our understanding of the enzymatic reactions has improved greatly via investigation of spectroscopic and chemical properties of heme and non-heme iron(IV)-oxo complexes. In this Account, reactivities of synthetic iron(IV)-oxo porphyrin pi-cation radicals and mononuclear non-heme iron(IV)-oxo complexes in oxygenation reactions have been discussed as chemical models of cytochrome P450 and non-heme iron enzymes. These results demonstrate how mechanistic developments in biomimetic research can help our understanding of dioxygen activation and oxygen atom transfer reactions in nature.     

Heme-copper/dioxygen adduct formation, properties, and reactivity

This Account focuses on our recent developments in synthetic heme/copper/O 2 chemistry, potentially relevant to the mechanism of action of heme-copper oxidases (e.g., cytochrome c oxidase) and to dioxygen activation chemistry. Methods for the generation of O 2 adducts, which are high-spin heme(Fe (III))-peroxo-Cu (II) complexes, are described, along with a detailed structural/electronic characterization of one example. The coordination mode of the O 2-derived heme-Cu bridging group depends upon the copper-ligand environment, resulting in micro-(O 2 (2-)) side-on to Fe (III) and end-on to Cu (II) (micro-eta (2):eta (1)) binding for cases having N 4 tetradentate ligands but side-on/side-on (micro-eta (2):eta (2)) micro-peroxo coordination with tridentate copper chelates. The dynamics of the generation of Fe (III)-(O 2 (2-))-Cu (II) complexes are known in some cases, including the initial formation of a short-lived superoxo (heme)Fe (III)(O 2 -) intermediate. Complexes with cross-linked imidazole-phenol "cofactors" adjacent to the copper centers have also been described. Essential investigations of heme-copper-mediated reductive O-O bond cleavage chemistry are ongoing.     

Mononuclear Cu-O2 complexes: geometries, spectroscopic properties, electronic structures, and reactivity

Using interwoven experimental and theoretical methods, detailed studies of several structurally defined 1:1 Cu-O 2 complexes have provided important fundamental chemical information useful for understanding the nature of intermediates involved in aerobic oxidations in synthetic and enzymatic copper-mediated catalysis. In particular, these studies have shed new light on the factors that influence the mode of O 2 coordination (end-on vs side-on) and the electronic structure, which can vary between Cu(II)-superoxo and Cu(III)-peroxo extremes.     

Dioxygen activation at non-heme iron: insights from rapid kinetic studies

One of the common biochemical pathways of binding and activation of dioxygen involves non-heme iron centers. The enzyme cycles usually start with an iron(II) or diiron(II) state and traverse via several intermediates (detected or postulated) such as (di)iron(III)-superoxo, (di)iron(III)-(hydro)peroxo, iron(III)iron(IV)-oxo, and (di)iron(IV)-oxo species, some of which are responsible for substrate oxidation. In this Account, we present results of kinetic and mechanistic studies of dioxygen binding and activation reactions of model inorganic iron compounds. The number of iron centers, their coordination number, and the steric and electronic properties of the ligands were varied in several series of well-characterized complexes that provided reactive manifolds modeling the function of native non-heme iron enzymes. Time-resolved cryogenic stopped-flow spectrophotometry permitted the identification of kinetically competent intermediates in these systems. Inner-sphere mechanisms dominated the chemistry of dioxygen binding, intermediate transformations, and substrate oxidation as most of these processes were controlled by the rates of ligand substitution at the iron centers.     

Reactions of aromatic N-heterocycles with d0fn-metal alkyl complexes supported by chelating diamide ligands

Aromatic heterocycles are a prominent feature within natural products and pharmaceuticals and considerable efforts are directed toward their synthesis and functionalization. These molecules also appear as unwanted impurities in carbon-based fuels, and processes that fragment them are of increasing interest. Early transition metal-carbon bonds show diverse reactivity toward aromatic heterocycles: researchers have reported both functionalization, relevant to synthetic efforts, and ring opening, relevant to their removal from fuels. In particular, chelating ferrocene-diamides possess unique electronic characteristics as ancillary ligands that enable a wide range of reactivity behaviors for the resulting metal complexes. In this Account, we describe our efforts to understand the reactivity of group 3 metal and uranium alkyl complexes supported by these organometallic ligands toward aromatic N-heterocycles. Two geometrically related ancillary ligands were investigated: 1,1'-ferrocenylene-diamides and pincer-type pyridine-diamides. A substrate-dependent behavior was observed. For example, all the benzyl metal complexes cleaved 1-methylimidazole. In the case of pyridines, differences in reactivity were identified: C-H activation and C-C coupling occurred with substituted pyridines, while alkyl transfer predominated with isoquinoline and chelating pyridines. The products of the C-C coupling or the alkyl-transfer reactions underwent subsequent hydrogen transfer: within the same ring for the substituted pyridines and between two different heterocycles for isoquinoline and chelating pyridines. The comparison between yttrium and lutetium benzyl complexes supported by ferrocene- or pyridine-diamide ligands indicated that similar reactions occurred for specific substrates (1-methylimidazole, 2-picoline, and isoquinoline). A broader range of reaction types and a larger substrate scope were identified, however, for the ferrocene than for the pyridine-type complexes. Based on the reactions discussed in this Account and on isolated examples drawn from the literature, we conclude that the ferrocene-diamides represent a versatile ligand framework. We propose that iron's ability to accommodate changes in the electronic density at the metal center more readily than classical supporting ligands leads to the privileged status of these organometallic ancillary ligands.     

Electronic structure and reactivity of three-coordinate iron complexes

[Reaction: see text]. The identity and oxidation state of the metal in a coordination compound are typically thought to be the most important determinants of its reactivity. However, the coordination number (the number of bonds to the metal) can be equally influential. This Account describes iron complexes with a coordination number of only three, which differ greatly from iron complexes with octahedral (six-coordinate) geometries with respect to their magnetism, electronic structure, preference for ligands, and reactivity. Three-coordinate complexes with a trigonal-planar geometry are accessible using bulky, anionic, bidentate ligands (beta-diketiminates) that steer a monodentate ligand into the plane of their two nitrogen donors. This strategy has led to a variety of three-coordinate iron complexes in which iron is in the +1, +2, and +3 oxidation states. Systematic studies on the electronic structures of these complexes have been useful in interpreting their properties. The iron ions are generally high spin, with singly occupied orbitals available for pi interactions with ligands. Trends in sigma-bonding show that iron(II) complexes favor electronegative ligands (O, N donors) over electropositive ligands (hydride). The combination of electrostatic sigma-bonding and the availability of pi-interactions stabilizes iron(II) fluoride and oxo complexes. The same factors destabilize iron(II) hydride complexes, which are reactive enough to add the hydrogen atom to unsaturated organic molecules and to take part in radical reactions. Iron(I) complexes use strong pi-backbonding to transfer charge from iron into coordinated alkynes and N 2, whereas iron(III) accepts charge from a pi-donating imido ligand. Though the imidoiron(III) complex is stabilized by pi-bonding in the trigonal-planar geometry, addition of pyridine as a fourth donor weakens the pi-bonding, which enables abstraction of H atoms from hydrocarbons. The unusual bonding and reactivity patterns of three-coordinate iron compounds may lead to new catalysts for oxidation and reduction reactions and may be used by nature in transient intermediates of nitrogenase enzymes.     

Molecular design of transition metal alkynyl complexes as building blocks for luminescent metal-based materials: structural and photophysical aspects

In this Account, the design and successful isolation of a series of soluble di- and polynuclear alkynyl complexes of selected metals with d(8) and d(10) electronic configurations are described. These organometallic complexes are found to exhibit rich photophysical and photochemical properties that are unique to the presence of the alkynyl ligand. By a systematic variation of the nature of the ligands, the metal centers, and certain structural features, the photophysical properties could be readily varied and their spectroscopic origins elucidated. Some of these complexes have been shown to be ideal building blocks for the design of luminescent organometallic oligomers and metal-based functional materials.     

Side-on end-on bound dinitrogen: an activated bonding mode that facilitates functionalizing molecular nitrogen

Molecular nitrogen is the source of all of the nitrogen necessary to sustain life on this planet. How it is incorporated into the biosphere is complicated by its intrinsic inertness. For example, biological nitrogen fixation takes N(2) and converts it into ammonia using various nitrogenase enzymes, whereas industrial nitrogen fixation converts N(2) and H(2) to NH(3) using heterogeneous iron or ruthenium surfaces. In both cases, the processes are energy-intensive. Is it possible to discover a homogeneous catalyst that can convert molecular nitrogen into higher-value organonitrogen compounds using a less energy-intensive pathway? If this could be achieved, it would be considered a major breakthrough in this area. In contrast to carbon monoxide, which is reactive and an important feedstock in many homogeneous catalytic reactions, the isoelectronic but inert N(2) molecule is a very poor ligand and not a common industrial feedstock, except for the above-mentioned industrial production of NH(3). Because N(2) is readily available from the atmosphere and because nitrogen is an essential element for the biosphere, attempts to discover new processes involving this simple small molecule have occupied chemists for over a century. Since the first discovery of a dinitrogen complex in 1965, inorganic chemists have been key players in this area and have contributed much fundamental knowledge on structures, binding modes, and reactivity patterns. For the most part, the synthesis of dinitrogen complexes relies on the use of reducing agents to generate an electron-rich intermediate that can interact with this rather inert molecule. In this Account, a facile reaction of dinitrogen with a ditantalum tetrahydride species to generate the unusual side-on end-on bound N(2) moiety is described. This particular process is one of a growing number of new, milder ways to generate dinitrogen complexes. Furthermore, the resulting dinitrogen complex undergoes a number of reactions that expand the known patterns of reactivity for coordinated N(2). This Account reviews the reactions of ([NPN]Ta)(2)(mu-H)(2)(mu-eta(1):eta(2)-N(2)), 2 (where NPN = PhP(CH(2)SiMe(2)NPh)(2)), with a variety of simple hydride reagents, E-H (where E-H = R(2)BH, R(2)AlH, RSiH(3), and Cp(2)ZrCl(H)), each of which results in the cleavage of the N-N bond to form various functionalized imide and nitride moieties. This work is described in the context of a possible catalytic cycle that in principle could generate higher-value nitrogen-containing materials and regenerate the starting ditantalum tetrahydride. How this fails for each particular reagent is discussed and evaluated.     

Reactions of late transition metal complexes with molecular oxygen

Limited natural resources, high energy consumption, economic considerations, and environmental concerns demand that we develop new technologies for the sustainable production of chemicals and fuels. New methods that combine the selective activation of C-H bonds of hydrocarbons with oxidation by a green oxidant such as molecular oxygen would represent huge advances toward this goal. The spectacular selectivity of transition metals in cleaving C-H bonds offers the potential for the direct use of hydrocarbons in the production of value-added organics such as alcohols. However, the use of oxygen, which is abundant, environmentally benign, and inexpensive (particularly from air), has proven challenging, and more expensive and less green oxidants are often employed in transition-metal-catalyzed reactions. Advances in the use of oxygen as an oxidant in transition-metal-catalyzed transformations of hydrocarbons will require a better understanding of how oxygen reacts with transition metal alkyl and hydride complexes. For alkane oxidations, researchers will need to comprehend and predict how metals that have shown particularly high activity and selectivity in C-H bond activation (e.g. Pt, Pd, Rh, Ir) will react with oxygen. In this Account, we present our studies of reactions of late metal alkyls and hydrides with molecular oxygen, emphasizing the mechanistic insights that have emerged from this work. Our studies have unraveled some of the general mechanistic features of how molecular oxygen inserts into late metal hydride and alkyl bonds along with a nascent understanding of the scope and limitations of these reactions. We present examples of the formation of metal hydroperoxide species M-OOH by insertion of dioxygen into Pt(IV)-H and Pd(II)-H bonds and show evidence that these reactions proceed by radical chain and hydrogen abstraction pathways, respectively. Comparisons with recent reports of insertion of oxygen into other Pd(II)-H complexes, and also into Ir(III)-H and Rh(III)-H complexes, point to potentially general mechanisms for this type of reaction. Additionally, we observed oxygen-promoted C-H and H-H reductive elimination reactions from five-coordinate Ir(III) alkyl hydride and dihydride complexes, respectively. Further, when Pd(II)Me(2) and Pt(II)Me(2) complexes were exposed to oxygen, insertion processes generated M-OOMe complexes. Mechanistic studies for these reactions are consistent with radical chain homolytic substitution pathways involving five-coordinate M(III) intermediates. Due to the remarkable ability of Pt(II) and Pd(II) to activate the C-H bonds of hydrocarbons (RH) and form M-R species, this reactivity is especially exciting for the development of partial alkane-oxidation processes that utilize molecular oxygen. Our understanding of how late transition metal alkyls and hydrides react with molecular oxygen is growing rapidly and will soon approach our knowledge of how other small molecules such as olefins and carbon monoxide react with these species. Just as advances in understanding olefin and CO insertion reactions have shaped important industrial processes, key insight into oxygen insertion should lead to significant gains in sustainable commercial selective oxidation catalysis.     

Synthesis,Characterization and Biological Evaluation of Transition Metal Complexes Derived from N,S Bidentate Ligands

Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3-methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal complexes formed were expected to have a general formula of [M(NS)₂] where M = Cu²⁺, Ni²⁺, and Zn²⁺. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1) and S2M3MBH (2) were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cell lines. Only the Cu(II) complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II) complexes have a strong DNA binding affinity.     

Bio-inorganic approach to hydrocarbon oxidation

Oxidation reactions mimicking the biological oxidative processes are summarized. A dioxygen molecule can be activated by way of reductive activation within a coordination sphere of transition metal complexes, and the resulting electrophilic oxo species, which can also be generated by treatment with an oxo transfer reagent (so-called “shunt path”), exhibit oxidizing ability just like an oxene species.     

Corrolazines: new frontiers in high-valent metalloporphyrinoid stability and reactivity

The activation of dioxygen and its analogues, such as hydrogen peroxide, by metalloporphyrins leads to the generation of high-valent metal-oxo species. This process is critically important to heme-catalyzed reactions, such as for cytochrome P450, and synthetic porphyrin-catalyzed oxidations. We have synthesized a new ring-contracted porphyrinoid system called a corrolazine that is designed to stabilize high oxidation states, including high-valent metal-oxo species. The corrolazine ligand stabilizes manganese(V) terminal oxo and terminal imido complexes for isolation, both of which are only transiently observed with normal porphyrin macrocycles. Examination of both oxygen atom transfer and hydrogen atom abstraction reactions for the Mn(V)-oxo complex has led to a number of mechanistic insights regarding these transformations. The activation of H 2O 2 to give the Mn(V)-oxo complex exhibits some dramatic and unexpected axial ligand effects that call into question the normal role of axial ligands in O-O bond cleavage pathways.     

Controlled oxidation of hydrocarbons by the membrane-bound methane monooxygenase: the case for a tricopper cluster

[Figure: see text]. The growing need for inexpensive methods to convert methane to methanol has sparked considerable interest in methods that catalyze this process. The integral membrane protein particulate methane monooxygenase (pMMO) mediates the facile conversion of methane to methanol in methanotrophic bacteria. Most evidence indicates that pMMO is a multicopper enzyme, and these copper ions support redox, dioxygen, and oxo-transfer chemistry. However, the exact identity of the copper species that mediates the oxo-transfer chemistry remains an area of intense debate. This highly complex enzyme is notoriously difficult to purify because of its instability outside the lipid bilayer and tendency to lose its essential metal cofactors. For this reason, pMMO has resisted both initial identification and subsequent isolation and purification for biochemical and biophysical characterization. In this Account, we describe evidence that pMMO is a multicopper protein. Its unique trinuclear copper cluster mediates dioxygen chemistry and O-atom transfer during alkane hydroxylation. Although a recent crystal structure did not show this tricopper cluster, we provide compelling evidence for such a cluster through redox potentiometry and EPR experiments on the "holo" enzyme in pMMO-enriched membranes. We also identify a site in the structure of pMMO that could accommodate this cluster. A hydrophobic pocket capable of harboring pentane, the enzyme's largest known substrate, lies adjacent to this site. In addition, we have designed and synthesized model tricopper clusters to provide further chemical evidence that a tricopper cluster mediates the enzyme's oxo-transfer chemistry. These biomimetic models exhibit similar spectroscopic properties and chemical reactivity to the putative tricopper cluster in pMMO. Based on computational analysis using density functional theory (DFT), triangular tricopper clusters are capable of harnessing a "singlet oxene" upon activation by dioxygen. An oxygen atom is then inserted via a concerted process into the C-H bond of an alkane in the transition state during hydroxylation. The turnover frequency and kinetic isotope effect predicted by DFT show excellent agreement with experimental data.     

Modularly designed transition metal PNP and PCP pincer complexes based on aminophosphines: synthesis and catalytic applications

Transition metal complexes are indispensable tools for any synthetic chemist. Ideally, any metal-mediated process should be fast, clean, efficient, and selective and take place in a catalytic manner. These criteria are especially important considering that many of the transition metals employed in catalysis are rare and expensive. One of the ways of modifying and controlling the properties of transition metal complexes is the use of appropriate ligand systems, such as pincer ligands. Usually consisting of a central aromatic backbone tethered to two two-electron donor groups by different spacers, this class of tridentate ligands have found numerous applications in various areas of chemistry, including catalysis, due to their combination of stability, activity, and variability. As we focused on pincer ligands featuring phosphines as donor groups, the lack of a general method for the preparation of both neutral (PNP) and anionic (PCP) pincer ligands using similar precursor compounds as well as the difficulty of introducing chirality into the structure of pincer ligands prompted us to investigate the use of amines as spacers between the aromatic ring and the phosphines. By introduction of aminophosphine and phosphoramidite moieties into their structure, the synthesis of both PNP and PCP ligands can be achieved via condensation reactions between aromatic diamines and electrophilic chlorophosphines (or chlorophosphites). Moreover, chiral pincer complexes can be easily obtained by using building blocks obtained from the chiral pool. Thus, we have developed a modular synthetic strategy with which the steric, electronic, and stereochemical properties of the ligands can be varied systematically. With the ligands in hand, we studied their reactivity towards different transition metal precursors, such as molybdenum, ruthenium, iron, nickel, palladium, and platinum. This has resulted in the preparation of a range of new pincer complexes, including various iron complexes, as well as the first heptacoordinated molybdenum pincer complexes and several pentacoordinated nickel complexes by using a controlled ligand decomposition pathway. In addition, we have investigated the use of some of the complexes as catalysts in different C-C coupling reactions: for example, the palladium PNP and PCP pincer complexes can be employed as catalysts in the well known Suzuki-Miyaura coupling, while the iron PNP complexes catalyze the coupling of aromatic aldehydes with ethyl diazoacetate under very mild reaction conditions to give selectively 3-hydroxyacrylates, which are otherwise difficult to prepare. While this Account presents an overview of current research on the chemistry of P-N bond containing pincer ligands and complexes, we believe that further investigations will give deeper insights into the reactivity and applicability of aminophosphine-based pincer complexes.     

Synthetic development and chemical reactivity of transition-metal silylene complexes

A variety of transition-metal complexes with terminal silylene ligands have become available in recent years, because of the discovery of several preparative methods. In particular, three general synthetic routes to these complexes have emerged, on the basis of anionic group abstraction, coordination of a free silylene, and alpha-hydrogen migration. The direct transformation of organosilanes to silylene ligands at a metal center (silylene extrusion) has also been observed, and this has further spurred the exploration of silylenes as ligands. This Account describes the synthetic development of silylene ligands in our laboratory and resulting investigations of stoichiometric and catalytic chemistry for these species.     

ENDOR of metalloenzymes

This Account examines the role of electron-nuclear double resonance (endor) spectroscopy in furthering our understanding of how metal ions function in biological systems. It briefly describes endor and electron spin-echo envelope modulation (eseem) spectroscopies and then illustrates the uses of endor with several case studies from our own research: cytochrome c peroxidase compound ES; ribonucleotide reductase intermediate X; allylbenzene-inactivated chloroperoxidase; the role of the [4Fe-4S](+) cluster in enzymes of the "radical S-adenosylmethionine" superfamily; dioxygen activation by heme enzymes. Finally, it briefly considers future developments.     

A Polysiloxide Complex with two Chromium(III) η2-Superoxo Moieties

The isolation and identification of intermediates formed in the course of the activation of dioxygen at transition metal centers reveals important mechanistic insights concerning such processes. We previously reported the reaction of the dinuclear Cr^II complex [L₂Cr₂(MeCN)₂][Li(MeCN)]₂ (L=PhSi(OSiPh₂O⁻)₃) ( 5 ) with dioxygen, which resulted in the formation of the Cr^IV oxo complex [L₂Cr₂O₂][Li(THF)₂]₂ ( 6 ), as the final room temperature stable product. Here we now report the isolation and characterization of an intermediate en route to 6 , namely the dinuclear Cr^III superoxo complex [L₂Cr₂(O₂)₂][Li(MeCN)]₂ ( 7 ). 7 is the first example of a structurally characterized dinuclear Cr^III superoxo complex with two independent side-on bound superoxo ligands. Reactivity studies outline the capability of this superoxo complex to activate weak O−H bonds.     

Direct functionalization of M-C (M = Pt(II), Pd(II)) bonds using environmentally benign oxidants, O2 and H2O2

Atom economy and the use of "green" reagents in organic oxidation, including oxidation of hydrocarbons, remain challenges for organic synthesis. Solutions to this problem would lead to a more sustainable economy because of improved access to energy resources such as natural gas. Although natural gas is still abundant, about a third of methane extracted in distant oil fields currently cannot be used as a chemical feedstock because of a dearth of economically and ecologically viable methodologies for partial methane oxidation. Two readily available "atom-economical" "green" oxidants are dioxygen and hydrogen peroxide, but few methodologies have utilized these oxidants effectively in selective organic transformations. Hydrocarbon oxidation and C-H functionalization reactions rely on Pd(II) and Pt(II) complexes. These reagents have practical advantages because they can tolerate moisture and atmospheric oxygen. But this tolerance for atmospheric oxygen also makes it challenging to develop novel organometallic palladium and platinum-catalyzed C-H oxidation reactions utilizing O(2) or H(2)O(2). This Account focuses on these challenges: the development of M-C bond (M = Pt(II), Pd(II)) functionalization and related selective hydrocarbon C-H oxidations with O(2) or H(2)O(2). Reactions discussed in this Account do not involve mediators, since the latter can impart low reaction selectivity and catalyst instability. As an efficient solution to the problem of direct M-C oxidation and functionalization with O(2) and H(2)O(2), this Account introduces the use of facially chelating semilabile ligands such as di(2-pyridyl)methanesulfonate and the hydrated form of di(2-pyridyl)ketone that enable selective and facile M(II)-C(sp(n)) bond functionalization with O(2) (M = Pt, n = 3; M = Pd, n = 3 (benzylic)) or H(2)O(2) (M = Pd, n = 2). The reactions proceed efficiently in protic solvents such as water, methanol, or acetic acid. With the exception of benzylic Pd(II) complexes, the organometallic substrates studied form isolable high-valent Pt(IV) or Pd(IV) intermediates as a result of an oxidant attack at the M(II) atom. The resulting high-valent M(IV) intermediates undergo C-O reductive elimination, leading to products in high yields. Guidelines for the synthesis of products containing other C-X bonds (X = OAc, Cl, Br) while using O(2) or H(2)O(2) as oxidants are also discussed. Although the M(II)-C bond functionalization reactions including high-valent intermediates are well understood, the mechanism for the aerobic functionalization of benzylic Pd(II) complexes will require a more detailed exploration. Importantly, further optimization of the systems suitable for stoichiometric M(II)-C bond functionalization led to the development of catalytic reactions, including selective acetoxylation of benzylic C-H bonds with O(2) as the oxidant and hydroxylation of aromatic C-H bonds with H(2)O(2) in acetic acid solutions. Both reactions proceed efficiently with substrates that contain a directing heteroatom. This Account also describes catalytic methods for ethylene dioxygenation with H(2)O(2) using M(II) complexes supported by facially chelating ligands. Mechanistic studies of these new oxidation reactions point to important ways to improve their substrate scope and to develop "green" CH functionalization chemistry.     

Understanding how the thiolate sulfur contributes to the function of the non-heme iron enzyme superoxide reductase

Toxic superoxide radicals, generated via adventitious reduction of dioxygen, have been implicated in a number of disease states. The cysteinate-ligated non-heme iron enzyme superoxide reductase (SOR) degrades superoxide via reduction. Biomimetic analogues which provide insight into why nature utilizes a trans-thiolate to promote SOR function are described. Spectroscopic and/or structural characterization of the first examples of thiolate-ligated Fe (III)-peroxo complexes provides important benchmark parameters for the identification of biological intermediates. Oxidative addition of superoxide is favored by low redox potentials. The trans influence of the thiolate appears to significantly weaken the Fe-O peroxo bond, favoring proton-induced release of H 2O 2 from a high-spin Fe(III)-OOH complex.