Influence of Thiolate Ligands on Reductive N−O Bond Activation. Probing the O₂⁻ Binding Site of a Biomimetic Superoxide Reductase Analogue and Examining the Proton-Dependent Reduction of Nitrite

Abstract

Nitric oxide (NO) is frequently used to probe the substrate–binding site of “spectroscopically silent” non-heme Fe2+ sites of metalloenzymes, such as superoxide reductase (SOR). Herein we use NO to probe the superoxide binding site of our thiolate–ligated biomimetic SOR model [FeII(SMe2N4(tren))]+ (1). Like NO–bound trans cysteinate-ligated SOR (SOR-NO), the rhombic S= 3/2 EPR signal of NO–bound cis thiolate-ligated [Fe(SMe2N4(tren)(NO)]+ (2; g = 4.44, 3.54, 1.97), isotopically sensitive νNO(ν15NO) stretching frequency (1685(1640) cm−1), and 0.05 Å decrease in Fe–S bond length are shown to be consistent with the oxidative addition of NO to Fe(II) to afford an Fe(III)–NO− {FeNO}7 species containing high–spin (S= 5/2) Fe(III) antiferromagnetically coupled to NO− (S= 1). The cis versus trans positioning of the thiolate does not appear to influence these properties. Although it has yet to be crystallographically characterized, SOR-NO is presumed to possess a bent Fe-NO similar to that of 2 (Fe–N–O= 151.7(4)°). The N–O bond is shown to be more activated in 2 relative to N– and O–ligated {FeNO}7 complexes, and this is attributed to the electron donating properties of the thiolate ligand. Hydrogen bonding to the cysteinate sulfur attenuates N–O bond activation in SOR as shown by its higher νNO frequency (1721 cm−1). In contrast, the νO–O frequency of SOR peroxo intermediate and its analogues is not affected by H-bonds to the cysteinate sulfur, or other factors influencing the Fe–SR bond strength. These only influence the νFe–O frequency. Reactions between 1 and NO2− are shown to result in the proton–dependent heterolytic cleavage of an N–O bond. The mechanism of this reaction is proposed to involve both FeII–NO2− and {FeNO}6 intermediates similar to those implicated in the mechanism of NiR–promoted NO2− reduction.

Photoinitiated Reactivity of a Thiolate-Ligated, Spin-Crossover Nonheme {FeNO}7 Complex with Dioxygen

“…The more narrow signal centered at g = 2.00 is consistent with the {FeNO} 7 complex 2 , exhibiting well-resolved hyperfine coupling from the nitrogen atom of the NO ligand. The broader rhombic Fe III signals are consistent with previously characterized nonheme low-spin Fe III (NO 2 − ) complexes 21,22 and may represent different conformers of the Fe III (NO 2 − ) complex or byproducts of the oxidation reaction and nitrite complex decomposition. The presence of the {FeNO} 7 complex in the EPR spectrum is consistent with the relatively rapid decay of the iron(III)–nitrite complex at higher concentrations to regenerate the {FeNO} 7 complex along with S-oxygenated products, as shown in the CSI-MS analysis as well as the EPR spectrum of 4 generated via pathway B from Figure 5.…”

“…22,69 This elongation is indicative of a significant population of the high-spin ( S = 3/2) state for this {FeNO} 7 complex. These findings help to explain the observation of the two N–O vibrational modes and are in good agreement with variable-temperature magnetic susceptibility data collected for 2 (vide infra).…”

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

“…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).…”

Preparation of Non-heme {FeNO}7 Models of Cysteine Dioxygenase: Sulfur versus Nitrogen Ligation and Photorelease of Nitric Oxide

“…The structure reveals one molecule of NO• has displaced the CH 3 CN ligand and confirms that 1 readily binds NO•, providing strong support for the proposed site for O 2 binding in 1 during biomimetic sulfoxygenation. 3a Only one other complex ([(S Me2 N 4 (tren))Fe(NO)] + ) 5 besides 3 contains the N 4 S ligand environment of the NO-bound form of CDO.…”

“…These data are similar to other {FeNO} 7 complexes. 5,7,8 To our knowledge complexes 3 and 4 comprise the only known pair of structurally characterized {FeNO} 7 complexes that differ by the substitution of an N versus S donor in the Fe coordination sphere. We expected that further examination of 3 and 4 would provide fundamental insights regarding the influence of S versus N coordination on {FeNO} 7 complexes.…”