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(
6
); crystallographic data for a enzyme that hydroxylates camphor
have revealed that the camphor is held by the protein in close proximity to
the Fe(III) center
16
. (b) A 1-electron reduction of (
6
) gives a high spin, 5-
coordinate Fe(II) complex (
7
). (c) (
7
) binds to give a low spin complex
(
8
). (d) A second 1-electron reduction of the dioxygenated adduct (
8
) gives
what is probably a high spin Fe(III)-peroxide (
9
)
8,17
. (e). Heterolytic
cleavage of the oxygen-oxygen bond within (
9
), with consumption of
protons, generates water and a high-valent oxo-iron species (
10
), written
here as Fe(V)=O, although model studies favor a O=Fe(IV)(porp
+.
),
porphyrin cation-radical species
7-11
. (f) Incorporation of the O-atom into the
substrate gives the oxygenated product with concomitant regeneration of the
initial Fe(III) state (
5
). The net reaction is that shown in eq. (2); the 2-
electrons are supplied by NADPH, and involve coupling to flavin reductase
and putidaredoxin systems. The addition of the O-atom to
S
is usually
written as a “rebound” mechanism, involving H-atom abstraction from the
substrate by the Fe=O moiety and subsequent rebound of the OH group
7
.
The protein pocket, in which cytochrome P-450 is embedded together
with the amino-acid cysteine axial ligand, provides favorable and
presumably optimal conditions for monooxygenase activity.
In vitro
(i.e.
outside of a protein) metalloporphyrins, especially those containing naturally
occurring porphyrins such as PpIX, can undergo undesirable side-reactions
such as dimerization and aggregation and, under can be irreversibly
oxidized (e.g. Fe and Ru-porphyrins give species - see below) with
resulting loss of their oxygen-activating abilities. Efforts have thus been
made to minimize these undesirable effects by introducing substituent alkyl
or halogen substituents into, for example, the phenyl rings of the well
known, easily synthesized
meso
-tetraphenylporphyrin ligand such
modifications create steric hindrance against formation of species
(loosely called “dimerization”), but also, of course, change the
electrophilicity of the metal (or metal oxo) centre.
The majority of biomimetic studies, including the use of a plethora of
metal complexes, and not just metalloporphyrins, can be categorized and
rationalized in terms of the pathways illustrated in Figure 3, especially when
the so-called “shunt pathways”
A
and
B
are included. Basically, and of key
importance, the P-450 studies show that generation of a high-valent metal-
oxo species such as (
10
) is needed to mimic monooxygenase activity.
Clearly one way to achieve formation of model species akin to (
10
) via (
9
) is
to follow pathways (b) - (d), i.e. utilize a metalloporphyrin (or other metal
complex), and a reducing agent to supply the electrons
11-15,18-31
; a metal
(M) in oxidation state (III) could generate a species. This type of
system represents genuine monooxygenase-like character, i. e. is
employed; however, a problem arises in that both the substrate (
S
) and the
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