HIGH-VALENT Cr, Mn, AND Fe SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 335

confirmed by product analysis of the reaction mixture. Additionally, other
possible products such as sulfenic and sulfinic acids derived from Cys were not
observed. In the case of Met, no KIE was observed (Fig. 6.31b), which supports
the rate-determining step did not involve the loss of a hydrogen atom from
the compound. The sulfoxide product 2 from the reaction of the Ac-Met-NHt-
Bu compound with the ferryl species was determined. This is in agreement
with the results obtained in the reactions of the [Fe IV (O)(N4Py)] 2+ species with
aromatic sulfides [347]. Thus, an oxygen-atom transfer reaction mechanism was
proposed (Fig. 6.31b).
The reactivity of [Fe IV (O)(N4Py)] 2+ with model compounds derived from
aromatic amino acids, Trp and Tyr, has also been studied [334]. The decomposi-
tion rates of the ferryl species were three and four orders of magnitude faster
for Trp and Tyr, respectively, than the control reaction with the compounds. The
second-order rate constants were determined as 1.64 and 4.2 × 10 1 /M/s for Tyr
and Trp, respectively. The decomposition of [Fe IV (O)(N4Py)] 2+ by Ac-Trp-
NHtBu in the D 2 O/CD 3 CN solvent produced a KIE of 5.2 (Fig. 6.32a). This
deuterium KIE is similar to the KIE determined in the decomposition of
[Fe IV (O)(N4Py)] 2+ by the compounds derived from Gly and Cys (see Fig. 6.31).
This is consistent with the ET-PT mechanism proposed in Figure 6.32a. Signifi-
cantly, the KIE of 4.4 was determined for the oxidation of Trp in D 2 O by the
heme-containing iron enzyme tryptophan 2,3-dioxygenase [348]. In this study,
the removal of the indole proton was suggested as partially rate-determining.
The uV-vis spectroscopic results demonstrated a faster decomposition of the
ferryl species than the regeneration of the Fe II species (Fig. 6.32a). Products of
the reaction mixture indicate the addition of a single oxygen atom to the Trp
molecule, possibly located at position 3 of the indole ring. The results are similar
to the products formed in the oxidation of Trp by ClO 2 [349].
The Ac-Tyr-NHtBu compound had a high KIE of 29 for the decomposition
of [Fe IV (O)(N4Py)] 2+ in the D 2 O/CD 3 CN solvent (Fig. 6.32b). The generation
of a tyrosyl radical was proposed through a HAT rather than ET-PT (Fig.
6.32b). The proposed mechanism was supported by slower rate constants for
the ferryl species in the presence of the protected Tyr compounds, Ac-
Tyr(OAc)-NHtBu and Ac-Tyr(OMe)-NHtBu, having pseudo-first-order rate
constants of 1.3 × 10 −5 /s and 2.5 × 10 −5 /s, respectively. The Ac-Phe-NHtBu
compound also had a similar rate constant for the decomposition of the
[Fe IV (O)(N4Py)] 2+ species (see Table 6.5). The results clearly indicate the
involvement of the functional hydroxyl group of Ac-Tyr-NHtBu rather than
the electron-rich aromatic ring in the mechanism. The formation of the Tyr
radical was also supported by the determination of a trace amount of the
phenoxyl radical derived from Ac-Tyr-NHtBu using the EPR spectroscopy.
Significantly, a phenoxyl radical was also observed in the treatment of 2,4,6,-tri-
tert -butylphenol with [Fe IV (O)(N4Py)] 2+ . It appears the phenoxyl radicals
polymerized because no major oxidation products were identified.
The mechanism for the oxidation of GSH by [Fe IV (O)(N4Py)] 2+ has
also been studied [350]. Initially, the reaction immediately produced an