Oxidation of (Carboxyalkyl)thiopropionic Acid Derivatives by Hydroxyl Radicals. Mechanisms and Kinetics of Competitive Inter- and Intramolecular Formation of σ- and σ*-type Sulfuranyl Radicals

Abstract

The substituent effects on kinetics and yields of specific intermediates and products for the one-electron oxidation by hydroxyl radicals of various (carboxylalkyl)thiopropionic acid derivatives, 3-(methylthio)propionic acid (3-MTPA), 3,3‘-thiodipropionic acid (3,3‘-TDPA), 3-(carboxymethylthio)propionic acid (3-CMTPA), and 2-(carboxymethylthio)succinic acid (2-CMTPA) have been investigated employing pulse radiolysis on the nanosecond to microsecond time scale, and γ-radiolysis. For each derivative, the initial step was a formation of a hydroxysulfuranyl radical proceeding with absolute rate constants of k OH+3-MTPA = 9.1 × 109 M-1 s-1 and k OH+3,3‘-TDPA = 5.8 × 109 M-1 s-1. The subsequent formation of one-electron-oxidized intermediates such as dimeric sulfur−sulfur (S∴S)-three-electron-bonded and monomeric sulfur−carboxylate oxygen (S−O)-bonded sulfide radical cations strongly depended on pH, thioether concentration, and the availability of α- or β-positioned carboxylate functions. A spectral resolution procedure permitted the quantification of all transients present in solution at any time after the pulse. Whereas both (S∴S)- and (S−O)-bonded intermediates were formed for 3-MTPA at neutral solution, electrostatic repulsion nearly prohibited the formation of dimeric (S∴S)-bonded intermediates between an overall negatively charged sulfide radical cation of 3,3‘-TDPA and a second nonoxidized, overall twice negatively charged, molecule of 3,3‘-TDPA. Neither sulfide radical cation complex (S∴S)+ was observed for 3-CMTPA and 2-CMPTA rationalized by a fast decarboxylation of the α-positioned carboxylate group, yielding α-(alkylthio)alkyl radicals which were the only products optically observed on the pulse radiolysis time scale. For 3,3‘-TDPA, the conversion of the initially formed hydroxysulfuranyl radicals into the (S−O)-bonded intermediates occurred unimolecularly with k ≅ 108 s-1 whereas the formation of the (S∴S)-bonded intermediates proceeded bimolecularly with k = (1.9−2.0) × 108 M-1 s-1. These processes did not occur competitively, as the intercepts of plots of pseudo-first-order rate constants for the formation of the S∴S bonded intermediates as a function of thioether concentration were too small (2.7 × 107 s-1) to contain the unimolecular rate constant for the formation of the (S−O)-bonded intermediate (k = 108 s-1). Therefore, a mechanism was proposed according to which initially formed hydroxysulfuranyl radicals rapidly converted into the σ*-type (S−O)-bonded intermediate. Subsequently, these either converted into (S∴S)-bonded radical cation complexes via a displacement of the carboxylate oxygen by a second nonoxidized sulfide function, or reversibly ring-opened to yield the monomeric sulfur-centered radical cation. The latter either associated with a nonoxidized sulfide or irreversibly cyclized to a σ-type (S−O)-bonded sulfuranyl radical.

N-Terminal Decarboxylation as a Probe for Intramolecular Contact Formation in γ-Glu-(Pro)n-Met Peptides

“…Studies on the rate constants k S2.3 for reaction S2.3 as high as 10 7 –10 8 s –1 were reported in regard to five-membered S∴O-bonded rings in thiopropionic acids. 71 However, this range should be considered only as an upper limit to the six-membered (S∴O)-bonded rings that would be possible for the peptides in the current study because the formation of five-membered structures of intramolecularly (S∴O)-bonded radicals is kinetically preferred over six-membered structures. Particularly relevant evidence for this contrast between formation rates of five- vs six-membered (S∴O)-bonded rings was presented where such five-membered rings were observed in 3-(methylthio)propanol, but no such six-membered rings were observed in 4-(methylthio)butanol.…”

Effect of alkyl chain length on one-electron oxidation of bis(alkyl carboxylic acid) selenides: implication on their antioxidant ability

“…22,23 Considering the probable pathways for the decay of pSerOH as given in Scheme 2, k obs is expressed in terms of k d , k h and k s as shown in eqn (1). uncatalyzed spontaneous dissociation (k d ), acid catalyzed elimination of OH À from pSerOH (k h ) and reaction with another SeBA molecule (k s ).…”

“…22,23 Similarly, we expect that the radical cations of seleno carboxylic acid derivatives also undergo decarboxylation to generate a-(alkylseleno) alkyl radical. 22,23 Similarly, we expect that the radical cations of seleno carboxylic acid derivatives also undergo decarboxylation to generate a-(alkylseleno) alkyl radical.…”

Oxidative Degradation of Thiaproline Derivatives in Aqueous Solutions Induced by •OH Radicals

“…The initial reaction of COH with 1-3 is identical to those with simple aliphatic and substituted thioethers, [41] amino acids, and peptides containing a thioether group in that it leads to the formation of the hydroxysulfuranyl radical (1a-3a; Schemes 1-3, respectively). [42] At a low proton concentration ([H + ]ffi0.02 mm) and a high concentration (50 mm) of 1-3, decomposition of 1a-3a can occur, in principle, either by unimolecular dissociation to generate the monomeric sulfur radical cations (> S + C), which subsequently associate with 1-3 [Eqs.…”