Generation, structure and reactions of sulfenic acid anions

O’Donnell, Jennifer S.; Schwan, Adrian L.

doi:10.1080/1741599042000220761

Cited by 77 publications

(65 citation statements)

References 71 publications

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“…Consistent with the expectation that this process proceeds via the desired sulfenate ion 14a, when the reaction is conducted in the presence of excess methyl iodide, the characteristic 16,33 sulfenate trapping product 16 is obtained in 35% yield along with 15a (25%, Scheme 5). In the context of this reaction, it is useful to note that sulfenate ions are ambident nucleophiles that can react at either sulfur or oxygen.…”

Section: Resultssupporting

confidence: 68%

“…33 In the leinamycin rearrangement, the oxygen atom of the sulfenate is the nucleophile, whereas the sulfur atom serves as a nucleophile in typical reactions of this functional group with methyl iodide and other alkyl halides. 16,33,34 The ester derivatives (13b-d) also undergo fluoride-triggered rearrangement in THF to provide 15a in yields comparable to those obtained from 13a. Evidently, a good leaving group (e.g.…”

Section: Resultsmentioning

confidence: 94%

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Entering the leinamycin rearrangement via 2-(trimethylsilyl)ethyl sulfoxides

Keerthi

Gates

2007

Org. Biomol. Chem.

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Attack of cellular thiols on the antitumor natural product leinamycin is believed to generate a sulfenate intermediate that undergoes subsequent rearrangement to a DNA-alkylating episulfonium ion. Here, 2-(trimethylsilyl)ethyl sulfoxides were employed in a fluoride-triggered generation of sulfenate anions related to the putative leinamycin-sulfenate. The resulting sulfenates enter smoothly into a leinamycin-type rearrangement reaction to afford an episulfonium ion alkylating agent. The results provide evidence that the sulfenate ion is, indeed, a competent intermediate in the leinamycin rearrangement. Further, the molecules examined here may provide a foundation for the design of functional leinamycin analogues that bypass the unstable and synthetically challenging 1,2-dithiolan-3-one 1-oxide moiety found in the natural product.

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Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 94%

Entering the leinamycin rearrangement via 2-(trimethylsilyl)ethyl sulfoxides

Keerthi

Gates

2007

Org. Biomol. Chem.

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“…Because the above results suggested the presence of an oxidized sulfur at the active site of the air-sensitive species, we tested the hypothesis that a sulfenic acid moiety coordinates a copper ion using dimedone, a well-established agent for the selective detection of sulfenic acid (32,33). After reaction of sulfenic acids with dimedone, the total mass should increase by +138 Da due to irreversible and selective condensation, which can be observed via mass spectrometry (34).…”

Section: Resultsmentioning

confidence: 99%

Copper–sulfenate complex from oxidation of a cavity mutant ofPseudomonas aeruginosaazurin

Sieracki

Tian

Hadt

et al. 2014

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

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Metal-sulfenate centers are known to play important roles in biology and yet only limited examples are known due to their instability and high reactivity. Herein we report a copper-sulfenate complex characterized in a protein environment, formed at the active site of a cavity mutant of an electron transfer protein, type 1 blue copper azurin. Reaction of hydrogen peroxide with Cu(I)-M121G azurin resulted in a species with strong visible absorptions at 350 and 452 nm and a relatively low electron paramagnetic resonance g z value of 2.169 in comparison with other normal type 2 copper centers. The presence of a side-on copper-sulfenate species is supported by resonance Raman spectroscopy, electrospray mass spectrometry using isotopically enriched hydrogen peroxide, and density functional theory calculations correlated to the experimental data. In contrast, the reaction with Cu(II)-M121G or Zn(II)-M121G azurin under the same conditions did not result in Cys oxidation or copper-sulfenate formation. Structural and computational studies strongly suggest that the secondary coordination sphere noncovalent interactions are critical in stabilizing this highly reactive species, which can further react with oxygen to form a sulfinate and then a sulfonate species, as demonstrated by mass spectrometry. Engineering the electron transfer protein azurin into an active copper enzyme that forms a copper-sulfenate center and demonstrating the importance of noncovalent secondary sphere interactions in stabilizing it constitute important contributions toward the understanding of metal-sulfenate species in biological systems.bioinorganic chemistry | metalloprotein design | protein engineering | blue copper proteins | posttranslational modification T he presence of cysteine sulfenic acid (Cys-SOH) as a product of posttranslational oxidation of the cysteine thiol side chain has been found to play important roles in biology (1-6) in the context of metal coordination (7), enzyme-protein regulation (8, 9), redox signaling (1, 5), and gene regulation (10-13). Unlike its higher oxidation state counterparts, i.e., sulfinic (Cys-SO 2 ) and sulfonic (Cys-SO 3 ) acids, the sulfenic acid is inherently unstable and highly reactive and thus requires stabilization to operate in a controlled context in biological systems (1-5). For example, a crystal structure of a sulfenic acid form of SarZ, a redox active global transcriptional regulator in Staphylococcus aureus, revealed that cysteine sulfenic acid is stabilized through two hydrogen bonds with surrounding residues, and its reversible oxidation-reduction allows redox-mediated virulence regulation in S. aureus (13).Because of the inherent instability and high reactivity, few examples of cysteine sulfenic acid have been observed in metalbinding sites in proteins (7,14). Nature has evolved proteins to allow metal ions to coordinate sulfenic acids, resulting in interesting functions. For example, nitrile hydratase, a metalloenzyme which has long found utility in the industrial synthesis of acrylamide (15...

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“…[5] Access to transient sulfenates is usually by chemically induced release from a stable sulfoxide. Sulfenates are prochiral and have been probed for their chemical reactivity, [4] organometallic chemistry [6] and nucleophilic chemistry, [7] the latter primarily taking the form of alkylation at sulfur to provide sulfoxide. Recent work has focussed on enantio- [8,9] and diastereoselective sulfoxide formation.…”

mentioning

confidence: 99%

“…[3] The sulfenate anion is the conjugate base of a sulfenic acid (Figure 1). [4] Both of these entities have a reputation for being transient and their isolation is possible but only if the compound possesses certain structural features. [5] Access to transient sulfenates is usually by chemically induced release from a stable sulfoxide.…”

mentioning

confidence: 99%