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2
Fe
ll
Fe
lll
2e
-
from
cofactor
H
+
,1e
-
from
NADH
Fe
ll
Fe
lll
R
H
Fe
IV
= O(porph
•
)
for heme enzymes
Fe
IV
2
O
2
for MMO
Fe
V
= O(OH)
=
Fe
V
Fe
lV
=
for Rieske
dioxygenases
Figure 6.23.
Generalized mechanistic scheme for oxygen activation at biological iron
sites (adapted from Shan and Que [260] with the permission of Elsevier Inc.).
indirect evidence suggests the Fe(IV)-oxo heme cation radical is the interme-
diate responsible for the monooxygenation of a substrate. DFT and quantum
mechanics/molecular mechanics (QM/MM) calculations on the activity of
P450 (models) also support the Fe(IV)-oxo cation as the intermediate in reac-
tions catalyzed by these enzymes [264, 269, 271]. Epoxidation, sulfoxodation,
aliphatic and aromatic hydroxylation, dehydrogenation, and N-dealkylation
are some of the reactions catalyzed by iron oxygenases [261, 274-277]. In a
recent study, the potential roles of amino acids residues (Arg172 and Arg38)
have been demonstrated in the transfer of protons from the ascorbate to the
ferryl oxygen in the heme enzyme ascorbate peroxidase (APX) [278]. Both
Arg172 and Arg38 had dual roles of forming ferryl species and of binding
ascorbate and also facilitating proton transfer between ferryl and ascorbate.
Mononuclear iron-containing enzymes are also involved in the activation
of O
2
to perform many metabolically important functions including the
hydroxylation of arene, the oxidation of aliphatic C-H bonds, and the
cis
-
dihydroxylation of arene double bonds [257, 260, 267, 279, 280]. Numerous
oxo-iron(IV) model complexes, exhibiting intermediate
S
= 1 spin states, have
been synthesized to understand the reaction mechanisms regarding the cata-
lytic cycles of many nonheme enzymes. Comparatively, known
S
= 2 oxo-
iron(IV) complexes are limited [12, 281, 282]. As suggested by the proposed
reaction mechanism (Fig. 6.23), enzymes in need of cofactors, such as tetrahy-
drobiopterin or 2-oxoacids (iron(IV)-oxo or iron(II)-peroxo species), are
formed through the simultaneous delivery of two electrons. Another example
is the generation of iron(IV)-oxo species in the catalytic cycles of four
2-oxoglutarate-dependent enzymes, in which high-valent iron species act as
the oxidant for the cleavage of the key C-H bond in many reactions [283]. The
use of NADH in methane monooxygenase or Rieske dioxygenases usually
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