HALOGENATED SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 106

as 1.0 × 10 8 /M/s and 1.4 × 10 8 /M/s, respectively. Similar rate constants suggest
common oxidation mechanisms for both thiols by ClO 2 .
The stoichiometry of the reaction between ClO 2 and Cys varied from 6 : 5
at low pH 3.6 to 2 : 10 at high pH 9.5 [163]. Cysteic acid was the major product
at low pH, while the disulfide was the major product at high pH [164, 172]. At
pH 6.7, the rate constant for the oxidation of CS − with ClO 2 was seven orders
of magnitude faster than the corresponding reaction with cystine (CSSC) at
pH 6.7. Therefore, no further oxidation of CSSC is expected. Based on the
substrate consumed and the concentrations of the products formed, other
products of the reaction may be thiosulfinate and thiosulfonate. A scheme
shown in Figure 3.17 was proposed [163]. Initially, a cysteine radical was
formed through a one-electron transfer process. The cysteine radicals further
reacted with another molecule of Cys to produce a ClO 2 -cysteinyl adduct. The
adduct was proposed to disproportionate by two pH-dependent pathways to
yield different products. The formation of cysteic acid from the oxidation of
disulfide (CSSC) was ruled out based on its slow reactivity with ClO 2 . In acidic
solution, sulfinic acid hydrolyzed to form sulfinic acid and HOCl. The rapid
reaction between these hydrolyzed products formed cysteine acid and Cl − . The
second pathway at high pH involved the reaction between the adduct and
CS − to give cystine and ClO − .
The stoichiometry and products of the reactions of Trp, Tyr, and His by ClO 2
have been performed [166, 171]. The stoichiometry of the reaction between
ClO 2 and Trp is presented in Equation (3.25):

− + .

(3.25)

2 ClO Trp H O ClO NFK HOCl H + + → + + +

2 2 2

In the proposed mechanism (Fig. 3.18), a one-electron transfer initially
yields a tryptophan radical cation and chlorite ion. The radical cation deproton-
ates to produce a neutral tryptophan radical, which is readily combined with a
second ClO 2 molecule to form a short-lived adduct (Fig. 3.18). This radical
decomposes to give the observed product, NFK (Fig. 3.18). The adduct reacts
with water to give an intermediate product A. The rearrangement of product
A forms the final product, NFK. Several other unidentified products were also
formed in the reaction of ClO 2 with Trp. More recently, product identification
of this reaction was conducted using mass analysis [166]. Molar ratios of ClO 2
to Trp were changed from 0.25 to 4.0 in the presence and absence of oxygen in
the reaction system. In excess ClO 2 , fumaric and oxalic acids were the abundant
products. Minor products were 2-aminobenzoic acid, N -formylanthranilic acid,
and 2-(2-oxoindolin-3-ylidene) acetic acid. Such products suggest the carbon-
carbon bond breaking of molecules during the reaction. Different kinds of
products were also observed in the reactions of His and Tyr with ClO 2 [166].
The reactions of Tyr, N -acetyltyrosine (NAT), and DOPA have been exam-
ined in the pH range from 4 to 7 [168]. Similar to the reaction of Trp with ClO 2 ,
the oxidation of 1 mol of Tyr and NAT consumed 2 mol of ClO 2 each and