Oxygen Activation by Mononuclear Mn, Co, and Ni Centers in Biology and Synthetic Complexes

The active sites of metalloenzymes that catalyze O2-dependent reactions generally contain iron or copper ions. However, several enzymes are capable of activating O2 at manganese or nickel centers instead, and a handful of dioxygenases exhibit activity when substituted with cobalt. This minireview summarizes the catalytic properties of oxygenases and oxidases with mononuclear Mn, Co, or Ni active sites, including oxalate-degrading oxidases, catechol dioxygenases, and quercetin dioxygenase. In addition, recent developments in the O2 reactivity of synthetic Mn, Co, or Ni complexes are described, with an emphasis on the nature of reactive intermediates featuring superoxo-, peroxo-, or oxo-ligands. Collectively, the biochemical and synthetic studies discussed herein reveal the possibilities and limitations of O2 activation at these three “overlooked” metals

Bimetallic Complexes Supported by a Redox-Active Ligand with Fused Pincer-Type Coordination Sites

The remarkable chemistry of mononuclear complexes featuring tridentate, meridionally chelating “pincer” ligands has stimulated the development of ligand frameworks containing multiple pincer sites. Here, the coordination chemistry of a novel pentadentate ligand (LN3O2) that provides two closely spaced NNO pincer-type compartments fused together at a central diarylamido unit is described. The trianionic LN3O2 chelate supports homobimetallic structures in which each M(II) ion (M = Co, Cu, Zn) is bound in a meridional fashion by the bridging diarylamido N atom and O,N-donors of the salicyaldimine arms. The metal centers are also coordinated by a mono- or bidentate auxiliary ligand (Laux), resulting in complexes with the general form [M2(LN3O2)(Laux)2]+ (where Laux = 1-methyl-benzimidazole (1MeBI), 2,2′-bipyridine (bpy), 4,4′-dibromo-2,2′-bipyridine (bpyBr2), or (S)-2-(4-isopropyl-4,5-dihydrooxazolyl)pyridine (S-iPrOxPy)). The fused nature of the NNO pincer sites results in short metal–metal distances ranging from 2.70 Å for [Co2(LN3O2) (bpy)2]+ to 3.28 Å for [Zn2(LN3O2) (bpy)2]+, as revealed by X-ray crystallography. The complexes possess C2 symmetry due to the twisting of the aryl rings of the μ-NAr2 core; spectroscopic studies indicate that chiral Laux ligands, such as S-iPrOxPy, are capable of controlling the helical sense of the LN3O2 scaffold. Since the four- or five-coordinate M(II) centers are linked solely by the amido moiety, each features an open coordination site in the intermetallic region, allowing for the possibility of metal–metal cooperativity in small-molecule activation. Indeed, the dicobalt(II) complex [Co2(LN3O2) (bpyBr2)2]+ reacts with O2 to yield a dicobalt(III) species with a μ-1,2-peroxo ligand. The bpy-containing complexes exhibit rich electrochemical properties due to multiple metal- and ligand-based redox events across a wide (3.0 V) potential window. Using electron paramagnetic resonance (EPR) spectroscopy and density functional theory (DFT), it was determined that one-electron oxidation of [Co2(LN3O2) (bpy)2]+ results in formation of a S = 1/2 species with a LN3O2-based radical coupled to low-spin Co(II) centers

Synthesis of Homo- and Heterobimetallic Ni\u3csup\u3eII\u3c/sup\u3e–M\u3csup\u3eII\u3c/sup\u3e (M = Fe, Co, Ni, Zn) Complexes Based on an Unsymmetric Ligand Framework: Structures, Spectroscopic Features, and Redox Properties

Several homo- and heterobimetallic NiII–MII complexes (MII = Fe, Co, Ni, Zn) supported by an unsymmetric polydentate ligand (L13−) are reported (L13− is the trianion of 2-[bis(2-hydroxy-3,5-tert-butylphenyl)aminomethyl]-4-methyl-6-[(2-pyridylmethyl)iminomethyl]phenol). The L13− chelate provides two distinct coordination environments: a planar tridentate {N2O} site (A) and a tetradentate {NO3} site (B). Reaction of L13− with equimolar amounts of NiII and MII salts provides bimetallic complexes in which the NiII ion exclusively occupies the tetragonal A-site and the MII ion is found in the tripodal B-site. X-ray crystal structures revealed that the two metal centers are bridged by the central phenolate donor of L13− and an anionic X-ligand, where X = μ-1,1-acetate, hydroxide, or methoxide. The metal ions are separated by 3.0–3.1 Å in the MAMBX structures, where MA and MB indicate the ion located in the A and B sites, respectively, and X represents the second bridging ligand. Analysis of magnetic data and UV–Vis–NIR spectra indicate that, in all cases, the two metal ions adopt high-spin states in solution. The NiAII centers undergo one-electron reduction at −1.17 V vs. SCE, while the NiII and CoII ions in the phenolate-rich B-site are reduced at lower potentials. Significantly, the NiAII center possesses three open or labile coordination sites in a meridional geometry, which are generally occupied by solvent-derived ligands in the crystal structures. The NiMBX complexes serve as structural mimics of heterometallic Ni-containing sites in biology, such as the C-cluster of carbon monoxide dehydrogenase (CODH)

A Synthetic Model of the Nonheme Iron–Superoxo Intermediate of Cysteine Dioxygenase

A nonheme Fe(II) complex (1) that models substrate-bound cysteine dioxygenase (CDO) reacts with O2 at −80 °C to yield a purple intermediate (2). Analysis with spectroscopic and computational methods determined that 2 features a thiolate-ligated Fe(III) center bound to a superoxide radical, mimicking the putative structure of a key CDO intermediate

A Synthetic Model of the Putative Fe(II)-Iminobenzosemiquinonate Intermediate in the Catalytic Cycle of \u3cem\u3eo\u3c/em\u3e-Aminophenol Dioxygenases

The oxidative ring cleavage of aromatic substrates by nonheme Fe dioxygenases is thought to involve formation of a ferrous–(substrate radical) intermediate. Here we describe the synthesis of the trigonal-bipyramdial complex Fe(Ph2Tp)(ISQtBu) (2), the first synthetic example of an iron(II) center bound to an iminobenzosemiquinonate (ISQ) radical. The unique electronic structure of this S = 3/2 complex and its one-electron oxidized derivative ([3]+) have been established on the basis of crystallographic, spectroscopic, and computational analyses. These findings further demonstrate the viability of Fe2+–ISQ intermediates in the catalytic cycles of o-aminophenol dioxygenases

Preparation of a Semiquinonate-Bridged Diiron(II) Complex and Elucidation of its Geometric and Electronic Structures

The synthesis and crystal structure of a diiron(II) complex containing a bridging semiquinonate radical are presented. The unique electronic structure of this S = 7/2 complex is examined with spectroscopic (absorption, EPR, resonance Raman) and computational methods

Spectroscopic and Computational Studies of Reversible O\u3csub\u3e2\u3c/sub\u3e Binding by a Cobalt Complex of Relevance to Cysteine Dioxygenase

The substitution of non-native metal ions into metalloenzyme active sites is a common strategy for gaining insights into enzymatic structure and function. For some nonheme iron dioxygenases, replacement of the Fe(II) center with a redox-active, divalent transition metal (e.g., Mn, Co, Ni, Cu) gives rise to an enzyme with equal or greater activity than the wild-type enzyme. In this manuscript, we apply this metal-substitution approach to synthetic models of the enzyme cysteine dioxygenase (CDO). CDO is a nonheme iron dioxygenase that initiates the catabolism of L-cysteine by converting this amino acid to the corresponding sulfinic acid. Two mononuclear Co(II) complexes (3 and 4) have been prepared with the general formula [Co2+(TpR2)(CysOEt)] (R = Ph (3) or Me (4); TpR2 = hydrotris(pyrazol-1-yl)borate substituted with R-groups at the 3- and 5-positions, and CysOEt is the anion of L-cysteine ethyl ester). These Co(II) complexes mimic the active-site structure of substrate-bound CDO and are analogous to functional iron-based CDO models previously reported in the literature. Characterization with X-ray crystallography and/or 1H NMR spectroscopy revealed that 3 and 4 possess five-coordinate structures featuring facially-coordinating TpR2 and S,N-bidentate CysOEt ligands. The electronic properties of these high-spin (S = 3/2) complexes were interrogated with UV-visible absorption and X-band electron paramagnetic resonance (EPR) spectroscopies. The air-stable nature of complex 3 replicates the inactivity of cobalt-substituted CDO. In contrast, complex 4 reversibly binds O2 at reduced temperatures to yield an orange chromophore (4-O2). Spectroscopic (EPR, resonance Raman) and computational (density functional theory, DFT) analyses indicate that 4-O2 is a S = 1/2 species featuring a low-spin Co(III) center bound to an end-on (η1) superoxo ligand. DFT calculations were used to evaluate the energetics of key steps in the reaction mechanism. Collectively, these results have elucidated the role of electronic factors (e.g., spin-state, d-electron count, metal–ligand covalency) in facilitating O2 activation and S-dioxygenation in CDO and related models

Dioxygen Reactivity of Biomimetic Fe(II) Complexes with Noninnocent Catecholate, \u3cem\u3eo\u3c/em\u3e-Aminophenolate, and \u3cem\u3eo\u3c/em\u3e-Phenylenediamine Ligands

This study describes the O2 reactivity of a series of high-spin mononuclear Fe(II) complexes each containing the facially coordinating tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP) ligand and one of the following bidentate, redox-active ligands: 4-tert-butylcatecholate (tBuCatH–), 4,6-di-tert-butyl-2-aminophenolate (tBu2APH–), or 4-tert-butyl-1,2-phenylenediamine (tBuPDA). The preparation and X-ray structural characterization of [Fe2+(Ph2TIP)(tBuCatH)]OTf, [3]OTf and [Fe2+(Ph2TIP)(tBuPDA)](OTf)2, [4](OTf)2 are described here, whereas [Fe2+(Ph2TIP)(tBu2APH)]OTf, [2]OTf was reported in our previous paper [Bittner et al., Chem.—Eur. J. 2013, 19, 9686–9698]. These complexes mimic the substrate-bound active sites of nonheme iron dioxygenases, which catalyze the oxidative ring-cleavage of aromatic substrates like catechols and aminophenols. Each complex is oxidized in the presence of O2, and the geometric and electronic structures of the resulting complexes were examined with spectroscopic (absorption, EPR, Mössbauer, resonance Raman) and density functional theory (DFT) methods. Complex [3]OTf reacts rapidly with O2 to yield the ferric-catecholate species [Fe3+(Ph2TIP)(tBuCat)]+ (3ox), which undergoes further oxidation to generate an extradiol cleavage product. In contrast, complex [4]2+ experiences a two-electron (2e–), ligand-based oxidation to give [Fe2+(Ph2TIP)(tBuDIBQ)]2+ (4ox), where DIBQ is o-diiminobenzoquinone. The reaction of [2]+ with O2 is also a 2e– process, yet in this case both the Fe center and tBu2AP ligand are oxidized; the resulting complex (2ox) is best described as [Fe3+(Ph2TIP)(tBu2ISQ)]+, where ISQ is o-iminobenzosemiquinone. Thus, the oxidized complexes display a remarkable continuum of electronic structures ranging from [Fe3+(L2–)]+ (3ox) to [Fe3+(L•–)]2+ (2ox) to [Fe2+(L0)]2+ (4ox). Notably, the O2 reaction rates vary by a factor of 105 across the series, following the order [3]+ \u3e [2]+ \u3e [4]2+, even though the complexes have similar structures and Fe3+/2+ redox potentials. To account for the kinetic data, we examined the relative abilities of the title complexes to bind O2 and participate in H-atom transfer reactions. We conclude that the trend in O2 reactivity can be rationalized by accounting for the role of proton transfer(s) in the overall reaction

Synthesis and Spectroscopic Characterization of High-Spin Mononuclear Iron(II) \u3cem\u3ep\u3c/em\u3e-Semiquinonate Complexes

Two mononuclear iron(II) p-semiquinonate (pSQ) complexes have been generated via one-electron reduction of precursor complexes containing a substituted 1,4-naphthoquinone ligand. Detailed spectroscopic and computational analysis confirmed the presence of a coordinated pSQ radical ferromagnetically coupled to the high-spin FeII center. The complexes are intended to model electronic interactions between (semi)quinone and iron cofactors in biology

Structural, Spectroscopic, and Electrochemical Properties of Nonheme Fe(II)-Hydroquinonate Complexes: Synthetic Models of Hydroquinone Dioxygenases

Using the tris(3,5-diphenylpyrazol-1-yl)borate (Ph2Tp) supporting ligand, a series of mono- and dinuclear ferrous complexes containing hydroquinonate (HQate) ligands have been prepared and structurally characterized with X-ray crystallography. The monoiron(II) complexes serve as faithful mimics of the substrate-bound form of hydroquinone dioxygenases (HQDOs) – a family of nonheme Fe enzymes that catalyze the oxidative cleavage of 1,4-dihydroxybenzene units. Reflecting the variety of HQDO substrates, the synthetic complexes feature both mono- and bidentate HQate ligands. The bidentate HQates cleanly provide five-coordinate, high-spin Fe(II) complexes with the general formula [Fe(Ph2Tp)(HLX)] (1X), where HLX is a HQate(1-) ligand substituted at the 2-position with a benzimidazolyl (1A), acetyl (1B and 1C), or methoxy (1D) group. In contrast, the monodentate ligand 2,6-dimethylhydroquinone (H2LF) exhibited a greater tendency to bridge between two Fe(II) centers, resulting in formation of [Fe2(Ph2Tp)2(μ-LF)(MeCN)]·[2F(MeCN)]. However, addition of one equivalent of “free” pyrazole (Ph2pz) ligand provided the mononuclear complex, [Fe(Ph2Tp)(HLF)(Ph2pz)]·[1F(Ph2pz)], which is stabilized by an intramolecular hydrogen bond between the HLF and Ph2pz donors. Complex 1F(Ph2pz) represents the first crystallographically-characterized example of a monoiron complex bound to an untethered HQate ligand. The geometric and electronic structures of the Fe/HQate complexes were further probed with spectroscopic (UV-vis absorption, 1H NMR) and electrochemical methods. Cyclic voltammograms of complexes in the 1X series revealed an Fe-based oxidation between 0 and −300 mV (vs. Fc+/0), in addition to irreversible oxidation(s) of the HQate ligand at higher potentials. The one-electron oxidized species (1Xoxox) were examined with UV-vis absorption and electron paramagnetic resonance (EPR) spectroscopies