HIGH-VALENT Cr, Mn, AND Fe SPECIES - Oxidation of Amino Acids, Peptides, and Proteins: Kinetics and Mechanism - page 331

[338]. Significantly, many of the Mn complexes have larger D O-H values than
[Fe IV (O)(N4Py)] 2+ , but the ferryl complex reacted much faster with DHA
than the Mn complexes. The unexpected larger relative reactivity of
[Fe IV O(N4Py)] 2+ was also observed in comparison to t BuOO • , [Fe IV (O)(TMP)]
(TPMP = tetramesitylporphinate), and Ru IV (O)(bpy) 2 (py)] 2+ (Fig. 6.28). The
results indicate the reactivity of [Fe IV (O)(N4Py)] 2+ was not only driven by
thermodynamics, but kinetic factors also participated in the enhancing ability
of [Fe IV (O)(N4Py)] 2+ to cleave the C-H bond in DHA. Furthermore, ligands
present in the nonheme iron complexes may thus determine the efficiency of
the Fe IV =O units to perform H-atom abstractions.
In recent years, the reactivity of [Fe IV O(N4Py)] 2+ with natural amino acids
has been performed [334, 335]. A series of model compounds, N -acetyl, tert -
butyl amide derivatives, of amino acids (Ac-AA-NHtBu) were synthesized
(Fig. 6.29) [343]. The compounds represent individual residues within a poly-
peptide chain in which the N-terminus was acetylated and a tert -butyl amide
was installed on the C-terminus [343]. The decomposition of [Fe IV (O)(N4Py)] 2+
in the presence of 10 equiv of the model compounds was followed. The mea-
sured pseudo-first-order rate constants ( k obs ) in a mixture of 1 : 1 H 2 O/MeCN
were determined (Table 6.5). The reactivity of [Fe IV (O)(N4Py)] 2+ varied over
five orders of magnitude. Comparatively, the kinetic rate constants for the
reactions of • OH with amino acids varied over only three orders of magnitude
[344]. This suggests [Fe IV (O)(N4Py)] 2+ may be more selective than • OH. The
values of the k obs and the relative rate constants ( k rel ) in Table 6.5 demonstrate
that Cys and Tyr had the highest reactivity with the ferryl species, followed by
Trp and Met. The derivatives of Gly, His, and Ser showed intermediate reactiv-
ity (Table 6.5). The reactivities of other model compounds were similar to the
control rate of the ferryl species.

O R O R

N N

H H

O O

P e R M m

1 Ala 8 Met 15 Ser

2 Val 9 Tyr 16 Thr

3 Phe 10 Trp 17 His

4 Leu 11 Gln 18 Arg

5 Pro 12 Lys 19 Asn

6 Gly 13 Glu 20 Ile

7 Cys 14 Asp

Figure 6.29. Structure of Ac-AA-NHtBu substrates that mimic amino acid residues of
polypeptides (adapted from Ekkati et al. [343] with the permission of Springer
Americas).