Electronic Structure of High-Spin Iron(III)−Alkylperoxo Complexes and Its Relation to Low-Spin Analogues:  Reaction Coordinate of O−O Bond Homolysis

Lehnert, Nicolai; Ho, Raymond Y. N.; Que, Lawrence; Solomon, Edward I.

doi:10.1021/ja011450+

Cited by 136 publications

(297 citation statements)

References 50 publications

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“…On the basis of the differences in the bonding that are apparent from the vibrational studies of S ϭ 1͞2 and S ϭ 3͞2 {FeNO} 7 , a high-spin ferric (hydro)peroxo intermediate is likely to be essential to promote breakdown via Fe-O rather O-O bond cleavage. This is in accord with recent studies by the Solomon and Que groups, which have shown that high-spin Fe 3ϩ -(alkyl)peroxo have much weaker Fe-O bonds and much stronger O-O bonds than their low-spin counterparts (43,44). Overall, characterization of the NO adducts of SOR indicates that the Fe spin state and the trans cysteinate ligand play important roles in effecting superoxide reduction and peroxide release at the SOR active site.…”

Section: Discussionsupporting

confidence: 89%

Nitric oxide binding at the mononuclear active site of reduced Pyrococcus furiosus superoxide reductase

Clay

Cosper

Jenney

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

133

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O ver the past 4 yr, evidence has accumulated for a novel pathway for detoxification of reactive oxygen species that is specific for anaerobic and microaerophilic microorganisms (1-3). The key enzyme in this pathway is superoxide reductase (SOR), which catalyzes the reduction of superoxide to hydrogen peroxide (4), with rubredoxin as the probable physiological electron donor (2, 5). Although all SORs have a ␤-barrel domain containing a unique type of mononuclear Fe center that serves as the site for superoxide reduction (6, 7), some have an additional N-terminal domain that contains an intrinsic rubredoxin-like mononuclear Fe site, which is ligated by four cysteines in a distorted tetrahedral arrangement analogous to that found in desulforedoxin (6). These two classes are conveniently referred to as 1Fe-and 2Fe-SORs, but they are also known by their trivial names, neelaredoxins and desulfoferrodoxins, respectively.Spectroscopic and crystallographic studies of the 1Fe-SOR from Pyrococcus furiosus (7-9) and the 2Fe-SOR from Desulfovibrio desulfuricans (6, 10, 11) have shown that the mononuclear iron active site is ligated by four equatorial histidines (3 N and 1␦N) and one axial cysteinate in a square-pyramidal arrangement. The sixth coordination site appears to be occupied by a monodentate glutamate in the oxidized state but is vacant or occupied by a weakly coordinated water molecule in the reduced state, thereby providing a site for superoxide binding and reduction. These structural studies, combined with recent mutagenesis and pulse radiolysis kinetic results (12-16), have led to the proposal for the catalytic mechanism shown in Fig. 1 Characterization of enzymatic intermediates is required for both detailed understanding of the mechanism of SOR and addressing the key questions of how and why the SOR active site preferentially catalyzes reduction rather than dismutation of superoxide. However, these intermediates are short lived and difficult to study experimentally. Nitric oxide (NO) has been extensively used as a substrate analog of molecular oxygen to form stable nitrosyl derivatives that provide insight into oxygen transport and activation intermediates in many heme (18-21) and nonheme (22-29) iron enzymes. Hence, we report here the formation and spectroscopic characterization of a stable NO-bound derivative of the reduced 1Fe-SOR from P. furiosus using the combination of EPR, UV-visible absorption, and variable-temperature, variable-field magnetic CD (VTVH MCD), resonance Raman, and Fourier transform IR (FTIR) spectroscopies. The structural and electronic characterization of the NO adduct of SOR facilitates understanding of how the active site is tuned for oxidative addition of superoxide and release rather than intraligand cleavage of the peroxide product. Materials and MethodsBiochemical Techniques and Sample Preparation. Recombinant natural abundance and 34 S globally enriched P. furiosus SOR was This paper was submitted directly (Track II) to the PNAS office.Abbreviations: SOR, superoxide reductase; V...

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Section: Discussionsupporting

confidence: 89%

Nitric oxide binding at the mononuclear active site of reduced Pyrococcus furiosus superoxide reductase

Clay

Cosper

Jenney

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

133

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“…In line with DFT calculations, [35][36][37] the low-spin iron(III) center plays a role in weakening the O-O bond and priming it for homolysis prior to substrate attack, a reactivity documented for 1a. 71 Comparison of 1a with activated bleomycin reveals major spectroscopic differences between the two complexes.…”

Section: Summary and Perspectivementioning

confidence: 66%

“…These features have been assigned to a ν(Fe-O 2 H) and a ν(O-O) vibration, respectively, and are considered to be the Raman signature of a low-spin Fe III -OOH intermediate. 20,24 In contrast, almost all high-spin mono-and diiron(III)-peroxo complexes typically exhibit [ [35][36][37] In support, Figure 3B shows the linear correlation between the ν(O-O) and the redox potential of the parent Fe II complex with ν(O-O) decreasing with redox potential. Thus, stabilization of the iron(III) oxidation state due to greater electron density at the metal center weakens the O-O bond.…”

Section: Resultsmentioning

confidence: 89%

“…Py5 ) 2,6-bis(methoxy(di(2-pyridyl))methyl)pyridine; pz ) pyrazole; SCE ) saturated calomel electrode; SOR ) superoxide reductase; TACN ) 1,4,7-triazacyclononane; TACNPy2 ) 1-di(2-pyridyl)methyl-4,7-dimethyl-1,4,7-triazacyclononane;tpen )N,N,N′,N′-tetrakis(2-pyridylmethyl)-1,2-diaminoethane; TPP ) meso-tetraphenylporphyrin dianion; Tp 3,5-iPr2 ) hydrotris(3,5-diisopropylpyrazolyl)borate; trispicMeen ) [33][34][35][36][37] Treatment of these low-spin Fe-OOH complexes with base converts them into new high-spin iron(III) species, 20,29-32, 38 and mixed isotope resonance Raman experiments strongly implicate a side-on bound peroxo ligand. 38 The only other established (η 2 -peroxo)iron complexes prior to these studies are those of Fe III (EDTA) 39 and Fe III (porphyrin).…”

Section: -Carboxylic Acid N-[2-(4′-imidazolyl)ethyl]amide;mentioning

confidence: 99%

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End-On and Side-On Peroxo Derivatives of Non-Heme Iron Complexes with Pentadentate Ligands: Models for Putative Intermediates in Biological Iron/Dioxygen Chemistry

et al. 2003

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Mononuclear iron(III) species with end-on and side-on peroxide have been proposed or identified in the catalytic cycles of the antitumor drug bleomycin and a variety of enzymes, such as cytochrome P450 and Rieske dioxygenases. Only recently have biomimetic analogues of such reactive species been generated and characterized at low temperatures. We report the synthesis and characterization of a series of iron(II) complexes with pentadentate N5 ligands that react with H 2 O 2 to generate transient low-spin Fe III −OOH intermediates. These intermediates have low-spin iron(III) centers exhibiting hydroperoxo-to-iron(III) charge-transfer bands in the 500−600-nm region. Their resonance Raman frequencies, ν O-O , near 800 cm -1 are significantly lower than those observed for high-spin counterparts. The hydroperoxo-to-iron(III) charge-transfer transition blue-shifts and the ν O-O of the Fe−OOH unit decreases as the N5 ligand becomes more electron donating. Thus, increasing electron density at the low-spin Mononuclear iron(III) peroxide species are implicated as intermediates in the mechanisms of oxygen activating biomolecules such as cytochrome P450, 1 heme oxygenase, 2 the antitumor drug bleomycin, 3 and Rieske dioxygenases, 4,5 as well as superoxide reductases from anaerobic bacteria. [6][7][8][9] Experimental evidence for some of these intermediates has

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“…5 bottom § The complete bleomycin ligand also includes a sugar moiety, a ␤-aminoalanine fragment, and a bithiazole tail. (33)(34)(35). From the homolysis calculations in Table 2 Left, the reaction energy ⌬E is much less sensitive to the ligand type, and the solvation effects are small.…”

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confidence: 99%

Non-heme iron enzymes: Contrasts to heme catalysis

Solomon

Decker

Lehnert

2003

Proc. Natl. Acad. Sci. U.S.A.

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222

187

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Non-heme iron enzymes catalyze a wide range of O2 reactions, paralleling those of heme systems. Non-heme iron active sites are, however, much more difficult to study because they do not exhibit the intense spectral features characteristic of the porphyrin ligand. A spectroscopic methodology was developed that provides significant mechanistic insight into the reactivity of non-heme ferrous active sites. These studies reveal a general mechanistic strategy used by these enzymes and differences in substrate and cofactor interactions dependent on their requirement for activation by iron. Contributions to O2 activation have been elucidated for non-heme relative to heme ligand sets, and major differences in reactivity are defined with respect to the heterolytic and homolytic cleavage of OOO bonds.

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Electronic Structure of High-Spin Iron(III)−Alkylperoxo Complexes and Its Relation to Low-Spin Analogues: Reaction Coordinate of O−O Bond Homolysis

Cited by 136 publications

References 50 publications

Nitric oxide binding at the mononuclear active site of reduced Pyrococcus furiosus superoxide reductase

Nitric oxide binding at the mononuclear active site of reduced Pyrococcus furiosus superoxide reductase

End-On and Side-On Peroxo Derivatives of Non-Heme Iron Complexes with Pentadentate Ligands: Models for Putative Intermediates in Biological Iron/Dioxygen Chemistry

Non-heme iron enzymes: Contrasts to heme catalysis

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