ion step follows the decarboxylation, which is consistent with the deuterium isotopic effects observed for thymine 7-hydroxylase which indicate that an irreversible step (or steps) occurs prior to the C-H bond breaking.395 It has also been shown for prolyl 4-hydroxylase that a substrate-derived radical is generated in the reaction, which is consistent with a rebound mechanism.437 It is important to point out that no oxygen intermediate (i.e., bridged superoxo or oxo-ferryl) has been observed for any R-KGdependent enzyme. This warrants future theoretical and experimental study. A detailed molecular mechanism has been proposed for IPNS based on spectroscopic and crystallographic studies.422 Resting IPNS/FeII is also 6C and thus relatively stable toward dioxygen. Substrate ACV binds directly to FeII IPNS through its thiolate group, providing an open coordination position at the FeII. O2 can then react to form an FeIII-superoxo intermediate. This intermediate is suggested422 to perform the first hydrogen-atom abstraction step and close the â-lactam ring, resulting in the formation of the first water molecule and generating an FeIVdO-II intermediate, which completes the second ringclosure process by hydrogen-atom abstraction forming a thiazolidine ring. Previously proposed mechanisms of ACCO involved direct binding of cosubstrate ascorbate to the iron before O2 as part of the oxygen activation process.438,439 The EPR and ESEEM studies of the NO complex of ACCO suggested a quite different molecular mechanism for ACCO.435 An FeIII-superoxo intermediate is proposed. Whether it is preceded by a 6C f 5C process with substrate binding is presently under study.440 This intermediate is thought to initiate a radical process by single hydrogen-atom abstraction or electron-coupled proton transfer (PT)ion or electron-coupled proton transfer (PT) from the bound amino group. The resulting substrate radical may undergo spontaneous conversion into products. The role of cosubstrate ascorbate is proposed to reduce the toxic peroxo byproduct to water. Alternatively, the two-electron reduction of FeIIIsuperoxo by the cosubstrate ascorbate could result in an FeIVdO-II intermediate which initiates the radical reaction.435 4. Rieske-Type Dioxygenases Biochemical Characterization. The Rieske ironsulfur center is a two iron-two sulfur cluster ([2Fe2S]) which has a 2His (on one iron), 2Cys (on the other iron) coordination environment, instead of the 4Cys present in plant ferredoxins. It plays a key role in the electron transport pathway in membranebound cytochrome complexes as well as in some dioxygenases.441 The latter are mainly comprised of two protein components: a reductase containing flavin and a ferredoxin [2Fe-2S], and a terminal oxygenase containing a Rieske [2Fe-2S] cluster and a non-heme iron active site.442 Except for the recently reported alkene monooxygenase that has a binuclear iron site in its terminal oxygenase,10 most of the Rieske-type oxygenases have a mononuclear iron site, which is believed to be the site of dioxygen activation and substrate oxygenation.442,443 The majority of the Rieske-type mononuclear non-heme oxygenases form a family of enzymes which are aromatic-ring-hydroxylating dioxygenases. These catalyze the regioand stereospecific cis-dihydroxylation of an aromatic ring using dioxygen and NAD(P)H (Table 1). Examples include benzene dioxygenase (BDO, EC 1.14.12.3),444 phthalate dioxygenase (PDO, EC 1.14.12.7),445 toluene dioxygenase (EC 1.14.12.11),446 and naphthalene 1,2-dioxygenase (NDO, EC 1.14.12.12),447 which initiate the aerobic degradation of aromatic compounds in the soil bacteria and are targets for bioengineering in bioremediation. This step is the first step in the pathway that ultimately leads to ring cleavage by the intraand extradiol dioxygenases (sections II.B.2 and II.C.1).443 Besides these bacterial dioxygenases, other Rieske-type mononuclear non-heme oxygenases include anthranilate 1,2-dioxygenase (EC 1.14.12.1),448 which deaminates and decarboxylates the substrate to produce catechol; chlorophenylacetate 3,4-dioxygenase (EC 1.14.2.13),449 which converts substrate to catechol with chloride elimination; and 4-methoxybenzoate O-demethylase (putidamonooxin),450 which catalyzes the conversion of 4-methoxybenzoic acid to 4-hydroxybenzoic acid and formaldehyde. The reductase component is usually a monomer (MW ) 12-15 kDa) and utilizes flavin to mediate ET from the two-electron donor NAD(P)H to the oneelectron acceptor [2Fe-2S] cluster and is specific to each terminal oxygenase; other electron donors do not support efficient oxygenation.442 The crystal structure of phthalate dioxygenase reductase is available.451 The terminal oxygenases are large protein aggregates (MW ) 150-200 kDa) containing either multiples of R subunits (BDO R2, PDO R4) or an equimolar combination of R and â subunits (toluene dioxygenase R2â2, NDO R3â3). The R subunits contain a Rieske [2Fe-2S] cluster and a catalytic non-heme FeII center. â subunits do not seem to be involved in the catalytic function (vide infra). Kinetics. Steady-state kinetic studies coupled with various rapid reaction studies of the partial reactions of PDO allowed Ballou et al. to propose a kinetic scheme (Scheme 15).443 On the basis of steady state 278 Chemical Reviews, 2000, Vol. 100, No. 1 Solomon et al.

Geometric and Electronic Structure/Function Correlations in Non-Heme Iron Enzymes

Magnetism of lanthanides in molecular materials with transition-metal ions and organic radicals.

The chemistry of copper is extremely rich because it can easily access Cu0, CuI, CuII, and CuIII oxidation states allowing it to act through one-electron or two-electron processes. As a result, both radical pathways and powerful two-electron bond forming pathways via organmetallic intermediates, similar to those of palladium, can occur. In addition, the different oxidation states of copper associate well with a large number of different functional groups via Lewis acid interactions or π-coordination. In total, these feature confer a remarkably broad range of activities allowing copper to catalyze the oxidation and oxidative union of many substrates.

Oxygen is a highly atom economical, environmentally benign, and abundant oxidant, which makes it ideal in many ways.1 The high activation energies in the reactions of oxygen require that catalysts be employed.2 In combination with molecular oxygen, the chemistry of copper catalysis increases exponentially since oxygen can act as either a sink for electrons (oxidase activity) and/or as a source of oxygen atoms that are incorporated into the product (oxygenase activity). The oxidation of copper with oxygen is a facile process allowing catalytic turnover in net oxidative processes and ready access to the higher CuIII oxidation state, which enables a range of powerful transformations including two-electron reductive elimination to CuI. Molecular oxygen is also not hampered by toxic byproducts, being either reduced to water, occasionally via H2O2 (oxidase activity) or incorporated into the target structure with high atom economy (oxygenase activity). Such oxidations using oxygen or air (21% oxygen) have been employed safely in numerous commodity chemical continuous and batch processes.3

However, batch reactors employing volatile hydrocarbon solvents require that oxygen concentrations be kept low in the head space (typically <5–11%) to avoid flammable mixtures, which can limit the oxygen concentration in the reaction mixture.4,5,6 A number of alternate approaches have been developed allowing oxidation chemistry to be used safely across a broader array of conditions. For example, use of carbon dioxide instead of nitrogen as a diluent leads to reduced flammability.5 Alternately, water can be added to moderate the flammability allowing even pure oxygen to be employed.6 New reactor designs also allow pure oxygen to be used instead of diluted oxygen by maintaining gas bubbles in the solvent, which greatly improves reaction rates and prevents the build up of higher concentrations of oxygen in the head space.4a,7 Supercritical carbon dioxide has been found to be advantageous as a solvent due its chemical inertness towards oxidizing agents and its complete miscibility with oxygen or air over a wide range of temperatures.8 An number of flow technologies9 including flow reactors,10 capillary flow reactors,11 microchannel/microstructure structure reactors,12 and membrane reactors13 limit the amount of or afford separation of hydrocarbon/oxygen vapor phase thereby reducing the potential for explosions.

Enzymatic oxidizing systems based upon copper that exploit the many advantages and unique aspects of copper as a catalyst and oxygen as an oxidant as described in the preceding paragraphs are well known. They represent a powerful set of catalysts able to direct beautiful redox chemistry in a highly site-selective and stereoselective manner on simple as well as highly functionalized molecules. This ability has inspired organic chemists to discover small molecule catalysts that can emulate such processes. In addition, copper has been recognized as a powerful catalyst in several industrial processes (e.g. phenol polymerization, Glaser-Hay alkyne coupling) stimulating the study of the fundamental reaction steps and the organometallic copper intermediates. These studies have inspiried the development of nonenzymatic copper catalysts. For these reasons, the study of copper catalysis using molecular oxygen has undergone explosive growth, from 30 citations per year in the 1980s to over 300 citations per year in the 2000s.

A number of elegant reviews on the subject of catalytic copper oxidation chemistry have appeared. Most recently, reviews provide selected coverage of copper catalysts14 or a discussion of their use in the aerobic functionalization of C–H bonds.15 Other recent reviews cover copper and other metal catalysts with a range of oxidants, including oxygen, but several reaction types are not covered.16 Several other works provide a valuable overview of earlier efforts in the field.17 This review comprehensively covers copper catalyzed oxidation chemistry using oxygen as the oxidant up through 2011. Stoichiometric reactions with copper are discussed, as necessary, to put the development of the catalytic processes in context. Mixed metal systems utilizing copper, such as palladium catalyzed Wacker processes, are not included here. Decomposition reactions involving copper/oxygen and model systems of copper enzymes are not discussed exhaustively. To facilitate analysis of the reactions under discussion, the current mechanistic hypothesis is provided for each reaction. As our understanding of the basic chemical steps involving copper improve, it is expected that many of these mechanisms will evolve accordingly.

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Aerobic Copper-Catalyzed Organic Reactions

The nature and characteristics of the CH/π interaction are discussed by comparison with other weak molecular forces such as the CH/O and OH/π interaction. The CH/π interaction is a kind of hydrogen bond operating between a soft acid CH and a soft base π-system (double and triple bonds, C6 and C5 aromatic rings, heteroaromatics, convex surfaces of fullerenes and nanotubes). The consequences of CH/π hydrogen bonds in supramolecular chemistry are reviewed on grounds of recent crystallographic findings and database analyses. The topics include intramolecular interactions, crystal packing (organic and organometallic compounds), host/guest complexes (cavity-type inclusion compounds of cyclodextrins and synthetic macrocyclic hosts such as calixarenes, catenanes, rotaxanes and pseudorotaxanes), lattice-inclusion type clathrates (including liquid crystals, porphyrin derivatives, cyclopentadienyl compounds and C60 fullerenes), enantioselective clathrate formation, catalytic enantioface discriminating reactions and solid-state photoreaction. The implications of the CH/π concept for crystal engineering and drug design are evident.

CH/π hydrogen bonds in crystals

Structure and Spectroscopy of Copper−Dioxygen Complexes

Binuclear copper(II) complexes, [Cu2(L1)(O2CMe)]·H2O (1), [Cu2(L5)(O2CMe)]·MeOH (2), [Cu2(L5)(O2CPh)]·H2O (3), [Cu2(L3)(O2CMe)](4), [Cu2(L2)(O2CMe)](5), and [Cu2(L4)(OMe)(MeOH)](6) were prepared, where the ligands H3Ln are 1 : 2 Schiff bases derived from 1,3-diaminopropan-2-ol and the carbonyl compounds acetylacetone (for L1), benzoylacetone (for L2), 3-ethoxymethylenepentane-2,4-dione (for L3), methyl acetoacetate (for L4), and salicylaldehyde (for L5). The crystal structures of (1)–(4) and (6) were determined by X-ray analysis. The results revealed that all the complexes are binuclear and bridged by alkoxide and carboxylate oxygens except for (6) in which the exogenous bridging group comprises two hydrogen-bridged methoxide ions. In all complexes co-ordination geometries are essentially planar, and the angle formed by the two co-ordination planes falls in the range 5–19° for (1)–(3) and (6), whereas the angle in (4) is 54.6° indicating a large distortion from a coplanar structure. Antiferromagnetic coupling is strong for (6)(–2J= 635 cm–1) as expected from its large Cu–O–Cu angle (137.7°). However, the other complexes showed much lower antiferromagnetism though their Cu–O–Cu angles differ little from that of (6). The low antiferromagnetism of (1)–(5) was rationalised in terms of countercomplementarity of the orbitals between two bridging groups which participate in the superexchange interaction.

Crystal structures and magnetism of binuclear copper(II) complexes with alkoxide bridges. Importance of orbital complementarity in spin coupling through two different bridging groups

Splitting of d-orbitals in square planar complexes of copper(II), nickel(II) and cobalt(II)

The syntheses and properties of copper(II) and nickel(II) complexes of N,N′-alkylenebis(3-formyl-5-methylsalicylaldimine (alkylene=ethylene, propylene, or trimethylene) are described. By the reaction of these complexes with other alkylenediamines (ethylenediamine or trimethylenediamine), mononuclear copper(II) and nickel(II) complexes of new N4O2-type macrocycles have been synthesized. These complexes react with additional copper(II) or nickel(II) ions to form binuclear copper(II) or nickel(II) complexes. The geometries and properties of these new complexes are discussed.

Binuclear Metal Complexes. III. Preparation and Properties of Mononuclear and Binuclear Copper(II) and Nickel(II) Complexes of New Macrocycles and Their Related Ligands

The electron transfer reactions between various copper(II) complexes and two-electron donors, such as ascorbic acid and 3,5-di-t-butylcatechol, were investigated Mononuclear copper(II) complexes with a distorted tetrahedral and a trigonal bipyramidal structure, and some binuclear complexes were readily reduced to copper(I) complexes by the two-electron donors, but not mononuclear planar copper(II) complexes The catalytic activities of these copper(II) complexes for the oxidation of 3,5-di-t-butylcatechol by O2 were studied in relation to the above reactions

Reaction between Various Copper(II) Complexes and Ascorbic Acid or 3,5-Di-t-butylcatechol

The effect of variation of structural factors on the spin-exchange interaction between copper(II) centers in dialkoxo-bridged dinuclear copper complexes were studied by the ab initio MO method with UHF formalism. The calculations were performed on di-μ-methoxotetraamminedicopper(II). The J-values were obtained as functions of Cu–O–Cu angle, dihedral angle between two coordination planes, planarity of bonds on the bridging oxygens, tetrahedral distortion of coordination planes, and the tilt of O–C bond from the O–O axis. The results demonstrated that the Cu–O–Cu angle most effectively affect the J-value but the other factors are less effective.

Sigeo Kida

Papers

Crystal structures and magnetism of binuclear copper(II) complexes with alkoxide bridges. Importance of orbital complementarity in spin coupling through two different bridging groups

Splitting of d-orbitals in square planar complexes of copper(II), nickel(II) and cobalt(II)

Binuclear Metal Complexes. III. Preparation and Properties of Mononuclear and Binuclear Copper(II) and Nickel(II) Complexes of New Macrocycles and Their Related Ligands

Reaction between Various Copper(II) Complexes and Ascorbic Acid or 3,5-Di-t-butylcatechol

Study of the Effect of Structural Factors on Magnetism of Di-μ-alkoxodicopper(II) Complexes by Ab Initio MO Calculations