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

Abstract

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.

Solvent‐ and Halide‐Induced (Inter)conversion between Iron(II)‐Disulfide and Iron(III)‐Thiolate Complexes

“…The UV/Vis spectrum of a CH 2 Cl 2 solution of [Fe 2 SS ] 2+ (Figure ) with an absorption band at around 450 nm ( ϵ ≈2700 L mol −1 ⋅cm −1 ) is similar to that observed in the solid‐state spectrum suggesting the preservation of the Fe II ‐disulfide complex in CH 2 Cl 2 solution. When [Fe 2 SS ] 2+ is dissolved in MeCN or DMF, a much more intense band is observed in the same region (at 449 and 475 nm ( ϵ ≈6800 L mol −1 ⋅cm −1 ), respectively), which can be assigned to a charge‐transfer transition from thiolate to Fe III . Two weaker features also appear at lower energies (at 641 and 745 nm in MeCN and at 605 and 710 nm in DMF).…”

“…These studies, supported by multiple experimental techniques in combination with DFT calculations, attest to how in coordinating solvents the Fe II -disulfide complex is partly or totally converted into the corresponding mononuclear Fe III (Figure 3) with an absorption band at around4 50 nm (e % 2700 Lmol À1 ·cm À1 )i ss imilart ot hat observed in the solidstate spectrum suggesting the preservation of the Fe II -disulfide complex in CH 2 Cl 2 solution.W hen [Fe 2 SS ] 2 + + is dissolved in MeCN or DMF,amuch more intense band is observed in the same region (at 449 and 475 nm (e % 6800Lmol À1 ·cm À1 ), respectively), which can be assigned to ac harge-transfer transition from thiolate to Fe III . [17] Twow eaker features also appear at lower energies (at 641 and 745 nm in MeCN and at 605 and 710 nm in DMF). Coherently,w hen as mall amount of DMF (corresponding to 1% v/v) is added to aC H 2 Cl 2 solutiono f [Fe 2 SS ] 2 + + ,t he progressive increase of the thiolatet oF e III band at 475 nm and of the two weaker visible transitions is observed, the process being complete in approximately 50 min, as shown in Figure S1 Conversely,t he mass spectra in MeCN and DMF display a + 1 main peak (at 634.1 and 706.9 m/z,r espectively) attributed to the mononuclear species, [Fe(LS)] + and [Fe(LS)(DMF)] + ,r espectively (Figure 4b,c).…”

Bio-inspired, Multifunctional Metal–Thiolate Motif: From Electron Transfer to Sulfur Reactivity and Small-Molecule Activation

“…Thiolates have actually been reported (i) to stabilize metal-(hydro/alkyl)peroxo, and -superoxo complexes, (ii) to decrease the activation barrier to O2 binding, (iii) to foster metal oxidation by significantly lowering its redox potential, (iv) to stabilize coordinatively unsaturated M II complexes suitable for O2 coordination, (v) to increase the basicity of M-bound oxo ligands, and (vi) to generate a labile position trans to the thiolate, which facilitates product release. [37][38][39] Despite these attractive properties, thiolates have been rarely used in the O2 activation domain, certainly because of their propensity to be oxidized into sulfenic or sulfinic acid in the presence of O2. Notably, coordination of the thiolate-rich H2L ligand enabled us the access to the first non-heme manganese and iron ORR catalysts.…”

Formation of a Reactive, Alkyl Thiolate-Ligated FeIII-Superoxo Intermediate Derived from Dioxygen

“…The addition of dry O 2 to 1 in THF at 25 °C causes an immediate color change from pale yellow to watermelon pink, with an associated shift in λ max to 510(1500) nm (Figure S3), and the growth of a signal ( g = 2.17, 2.11, 1.98) in the electron paramagnetic resonance (EPR) spectrum (Figure S4) consistent with the formation (in 93% yield) of low-spin (S = ½) [Fe III ( η 2 -S Me2 O)(S Me2 N 3 (Pr,Pr))] + ( 3 ). 30 Electrospray mass spectroscopy (ESI-MS) of isotopically labeled samples shows that the oxo of 3 is derived from 18 O 2 (Figure S5). Azide inhibits this reaction (Figures S6) indicating that O 2 must bind to the metal ion in order for oxo atom transfer to occur.…”