Mechanism of the cysteine sulfenic acid O-sulfenylation of 1,3-cyclohexanedione

Abstract

The density functionals B3LYP, B3PW91, M062X, and CAM-B3LYP with the 6-311+G(d,p) basis set predict the cysteine sulfenic acid O-sulfenylation of the s-cis-ketoenol tautomer of 1,3-cyclohexanedione proceeds through a cyclic 14-membered transition state structure containing three water molecules.

Mechanisms of Reactions of Sulfur Hydride Hydroxide: Tautomerism, Condensations, and C-Sulfenylation and O-Sulfenylation of 2,4-Pentanedione

“…As seen in the tautomerism mechanisms above, the condensation mechanisms with water molecules involve reactant complexes and product complexes that are better stabilized than the respective separated reactants and separated products. A comparison of the data in Table and Table SI 1 shows that increasing the number of water molecules increases the energy differences between the reactant complexes and the separated reactants, between the product complexes and the separated reactants, and between the product complexes and the separated products. − ,− …”

“…the reactant complexes). The incorporation of explicit water molecules helps to relieve strain, stabilize charges, form conformations that are favorable for reactivity, and set up proton relay networks to facilitate proton transfer from the oxygen in 1 to sulfur in tautomer 1a via water molecules in a Grotthuss-type mechanism. − ,− In the transition state structures, the water molecules act as both proton acceptors and proton donors.…”

“…Although other plausible mechanisms are possible, a reasonable mechanism for the O-sulfenylation of enolone 7 by hydrogen thioperoxide 1 may be similar to that for C-sulfenylation and involve conjugate addition of 1 to O2 in 7 (Figures 11 and 12). 12,13 Figure 12 shows that the O-sulfenylation of 7 by 1 involves a structurally different reactant complex than that predicted for C-sulfenylation (cf. Figures 11 and 12).…”

“…2,4-Pentanedione exists as a dynamic equilibrium mixture of tautomers, including the diketo tautomer ( 6 ) and the dominant enolone tautomer, (3 Z )-4-hydroxy-3-penten-2-one (ketoenol, 7 ) (Figure ). − Although the reactions of sulfenic acids with 1,3-dicarbonyl compounds are generally written as resulting in sulfenylation at carbon to form the thioether (sulfide) products, sulfenylation at oxygen to form the sulfenate ester products through the π-conjugated enolone system (eq ) or through different mechanisms is also reasonable. , In part because of the transient existence of 1 and sulfenic acids, there is a paucity of fundamental experimental studies of the mechanisms and products of their reactions with chemoselective 1,3-dicarbonyl reagents and with other functional groups. Because of the high reactivity of 1 and sulfenic acids, computational quantum chemistry is an excellent tool to investigate their properties and structures and the mechanisms of their tautomerism, condensation reactions, and C-sulfenylation and O-sulfenylation of 1,3-dicarbonyl compounds. − …”

S-nitrosylation of TRIM72 mends the broken heart: A molecular modifier-mediated cardioprotection

“…In the presence of aggressive oxidants such as hydrogen peroxide, the sulfhydryl group will be converted to sulfinic acid and sulfonic acid, which abolish the formation of disulfide bond, and thereby affect the protein function. Apart from oxidation, cysteine is also modulated by other post-translational modifications (PTMs), including S-glutathionylation [18], S-nitrosylation [19], sulfenylation [20], sulfinylation [21], S-ubiquitinylation [22], S-palmitoylation [23], 4-hydroxy-2-nonenal [24], and S-guanylation [25]. In spite of well-characterized chemical nature of cysteine residue, the functional consequences of these PTMs are much less understood, which has limited our ability to translate its application in the clinical arena.…”