How does cyanide inhibit superoxide reductase? Insight from synthetic Fe
            <sup>III</sup>
            N
            <sub>4</sub>
            S model complexes

Shearer, Jason; Fitch, Sarah; Kaminsky, Werner; Benedict, Jason B.; Scarrow, Robert C.; Kovacs, Julie A.

doi:10.1073/pnas.0637029100

Cited by 38 publications

(62 citation statements)

References 34 publications

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“…SCE), respectively, whereas CNligated 8 is reduced at a much more anodic potential of -805 mV versus SCE. [76] If cyanide were to cause an anodic shift in the redox potential of SOR by approximately the same amount (|∆E| Ն 470 mV), then the reduction potential of the catalytic iron center would fall well-below those of its biological reductants (center I, -236 mV versus SCE; rubredoxin, reported range -191 to -291 versus SCE). Thus, cyanide by preventing the enzyme from turning over because it prevents the regeneration of the reduced, catalytically active Fe 2+ state of SOR.…”

Section: Biomimetic Models Of Sormentioning

confidence: 98%

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Understanding the Mechanism of Superoxide Reductase Promoted Reduction of Superoxide

Brines

Kovacs

2006

Eur J Inorg Chem

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Superoxide reductases (SORs) are nonheme, iron-containing enzymes which reduce superoxide (O 2 -) to hydrogen peroxide (H 2 O 2 ) in anaerobic organisms. In contrast to the classical superoxide dismutases (SODs), SORs selectively reduce, rather than disproportionate, superoxide at an unusual [Fe(NHis) 4 SCys] catalytic site. Studies of the native enzyme and mutants have suggested the formation of a transient ferric-(hydro)peroxide intermediate in SOR's catalytic cycle, with subsequent protonation to yield hydrogen peroxide and a glutamate-bound ferric resting state. With the synthesis of small molecular model compounds of the enzyme's active site, analogous intermediates can be more thoroughly investigated in order to understand how the structure at the nonheme iron active site affects its function. Specific goals in-

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Section: Biomimetic Models Of Sormentioning

confidence: 98%

“…[76] Cyanide and azide do not bind to reduced 3, and do not prevent 3 from stoichiometrically reducing superoxide. (8), on the other hand, is S = 1/2 over a wide temperature range (2-300 K).…”

Section: Biomimetic Models Of Sormentioning

confidence: 99%

Understanding the Mechanism of Superoxide Reductase Promoted Reduction of Superoxide

Brines

Kovacs

2006

Eur J Inorg Chem

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“…The primary amine thiolate tren-ligand falls somewhere in between, favoring the +3 oxidation state more than the amine, but less than an alkoxide. 46 Since an open coordination site, and a moderately low redox-potential are both necessary for efficient, inner sphere, substrate (e.g superoxide) reduction to occur, the combination of a thiolate (as opposed to an alkoxide or amine) coordinated to iron (as opposed to cobalt), with primary (as opposed to secondary or tertiary) amines creates both of these optimum conditions needed for this chemistry to occur. This implies that the cysteinate ligand of the non-heme iron enzyme SOR plays an important role in promoting function.…”

Section: Comparison Of Redox Potentials-correlation With Apical Ligandmentioning

confidence: 99%

Comparison of structurally-related alkoxide, amine, and thiolate-ligated MII (M=Fe, Co) complexes: The influence of thiolates on the properties of biologically relevant metal complexes

Brines

Villar-Acevedo

Kitagawa

et al. 2008

Inorganica Chimica Acta

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Mechanistic pathways of metalloenzymes are controlled by the metal ion's electronic and magnetic properties, which are tuned by the coordinated ligands. The functional advantage gained by incorporating cysteinates into the active site of non-heme iron enzymes such as superoxide reductase (SOR) is not entirely understood. Herein we compare the structural and redox properties of a series of structurally-related thiolate, alkoxide, and amine-ligated Fe(II) complexes in order to determine how the thiolate influences properties critical to function. Thiolates are shown to reduce metal ion Lewis acidity relative to alkoxides and amines, and have a strong trans influence thereby helping to maintain an open coordination site. Comparison of the redox potentials of the structurally analogous compounds described herein indicates that alkoxide ligands favor the higher-valent Fe 3+ oxidation state, amine ligands favor the reduced Fe 2+ oxidation state, and thiolates fall somewhere in between. These properties provide a functional advantange for substrate reducing enzymes in that they provide a site at the metal ion for substrate to bind, and a moderate potential that facilitates both substrate reduction, and regeneration of the catalytically active reduced state. Redox potentials for structurally-related Co(II) complexes are shown to be cathodically-shifted relative to their Fe(II) analogues, making them ineffective reducing agents for substrates such as superoxide.

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“…59, 60, 62, 63, 72–74 Both ligands constrain the geometry so that added “substrates” are forced to bind cis to a thiolate (e.g., structures 3 and 4 , Scheme 4). 64, 65, 75, 76 For example, superoxide (O 2 − ) reacts with reduced [Fe II (N 4 S Me2 (tren))] + at low temperatures in the presence of a proton donor 59, 75, 77 to afford a metastable, low-spin ( S = 1/2; g ┴ = 2.14; g ║ = 1.97) hydroperoxo intermediate, [Fe III (N 4 S Me2 (tren))(OOH)] + ( 3 , Scheme 4; υ O-O = 784 cm −1 ). 54 Bis-thiolate ligated 2 (Scheme 3) was shown to bind L = N 3 − ( 4 ) and NO cis to one of the thiolates and trans to the other (Scheme 4).…”

Section: Introductionmentioning

confidence: 99%

Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate

et al. 2016

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Cysteinate oxygenation is intimately tied to the function of both cysteine dioxygenases (CDOs) and nitrile hydratases (NHases), and yet the mechanisms by which sulfurs are oxidized by these enzymes are unknown, in part because intermediates have yet to be observed. Herein, we report a five-coordinate bis-thiolate ligated Fe(III) complex, [FeIII(S2Me2N3-(Pr,Pr))]+ (2), that reacts with oxo atom donors (PhIO, IBX-ester, and H2O2) to afford a rare example of a singly oxygenated sulfenate, [FeIII(η2-SMe2O)(SMe2)N3(Pr,Pr)]+ (5), resembling both a proposed intermediate in the CDO catalytic cycle and the essential NHase Fe-S(O)Cys114 proposed to be intimately involved in nitrile hydrolysis. Comparison of the reactivity of 2 with that of a more electron-rich, crystallographically characterized derivative, [FeIIIS2Me2NMeN2amide(Pr,Pr)]− (8), shows that oxo atom donor reactivity correlates with the metal ion’s ability to bind exogenous ligands. Density functional theory calculations suggest that the mechanism of S-oxygenation does not proceed via direct attack at the thiolate sulfurs; the average spin-density on the thiolate sulfurs is approximately the same for 2 and 8, and Mulliken charges on the sulfurs of 8 are roughly twice those of 2, implying that 8 should be more susceptible to sulfur oxidation. Carboxamide-ligated 8 is shown to be unreactive towards oxo atom donors, in contrast to imine-ligated 2. Azide (N3−) is shown to inhibit sulfur oxidation with 2, and a green intermediate is observed, which then slowly converts to sulfenate-ligated 5. This suggests that the mechanism of sulfur oxidation involves initial coordination of the oxo atom donor to the metal ion. Whether the green intermediate is an oxo atom donor adduct, Fe-O═I-Ph, or an Fe(V)═O remains to be determined.

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How does cyanide inhibit superoxide reductase? Insight from synthetic Fe ^III N ₄ S model complexes

Cited by 38 publications

References 34 publications

Understanding the Mechanism of Superoxide Reductase Promoted Reduction of Superoxide

Understanding the Mechanism of Superoxide Reductase Promoted Reduction of Superoxide

Comparison of structurally-related alkoxide, amine, and thiolate-ligated MII (M=Fe, Co) complexes: The influence of thiolates on the properties of biologically relevant metal complexes

Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate

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How does cyanide inhibit superoxide reductase? Insight from synthetic Fe III N 4 S model complexes

Cited by 38 publications

References 34 publications

Understanding the Mechanism of Superoxide Reductase Promoted Reduction of Superoxide

Understanding the Mechanism of Superoxide Reductase Promoted Reduction of Superoxide

Comparison of structurally-related alkoxide, amine, and thiolate-ligated MII (M=Fe, Co) complexes: The influence of thiolates on the properties of biologically relevant metal complexes

Metal-Assisted Oxo Atom Addition to an Fe(III) Thiolate

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How does cyanide inhibit superoxide reductase? Insight from synthetic Fe ^III N ₄ S model complexes