Acid-catalyzed disproportionation of oxoiron(IV) porphyrins to give oxoiron(IV) porphyrin radical cations

Article abstract of DOI:10.1016/j.inoche.2011.03.044

Disproportionation of oxoiron(IV) porphyrin (Compound II) to oxoiron(IV) porphyrin radical cation (Compound I) was studied in three P450 model systems with different electronic structures. Direct conversion of Compound II to Compound I has been observed f

Full text of DOI:10.1016/j.inoche.2011.03.044

Inorganic Chemistry Communications 14 (2011) 968–970
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Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
Acid-catalyzed disproportionation of oxoiron(IV) porphyrins to give oxoiron(IV)
porphyrin radical cations
,1
⁎
⁎
Zhengzheng Pan , Martin Newcomb
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Disproportionation of oxoiron(IV) porphyrin (Compound II) to oxoiron(IV) porphyrin radical cation
(Compound I) was studied in three P450 model systems with different electronic structures. Direct
conversion of Compound II to Compound I has been observed for 5,10,15,20-tetrakis(2,6-dichlorophenyl)
porphyrin (TDCPP) in acid-catalyzed reactions in a mixed solvent of acetonitrile and water (1:1, v/v)
containing excess m-CPBA oxidant, with a second-order rate constant of (1.3 0.2)×102 M−1 s−1. The acid-
catalyzed disproportionation heavily depends on the electron demand of the substituted aryl groups on the
porphyrin macrocycle. The disproportionation equilibrium constants show drastic change for the three
porphyrin systems.
Received 4 February 2011
Accepted 18 March 2011
Available online 26 March 2011
Keywords:
Oxoiron
Disproportionation
Compound I
Compound II
P450 model
© 2011 Elsevier B.V. All rights reserved.
High-valent oxoiron porphyrin intermediates play important roles
in the mechanisms of hemoproteins such as the peroxidases and
cytochrome P450 enzymes [1,2]. Much effort has been devoted to the
enigmatic spectral and kinetic characteristics of highly oxidized states
[3–7]. Since the first report in 1981 [8], oxoiron(IV) porphyrin radical
cations, models for Compound I in enzymes including cytochrome
P450, have been generated and characterized for several different
porphyrin systems [7,9–11]. Another important oxoiron(IV) species,
referred to as Compound II in heme enzymes, involves a single-
electron oxidation from ferric porphyrin. In principle, Compound II
species could be formed by the homolytic O―O bond cleavage in an
acylperoxo–iron(III) complex [12]. Increasing interest has been
directed at the study of Compound II analogs, especially regarding
their reactivity towards organic substrates and the protonation of
ferryl–oxo bonds [11,13–17]. For example, oxoiron(IV) complexes
were also able to effect two-electron oxidations [17,18], which
suggests that they might serve as one of the active intermediates in
oxygen transfer process by cytochrome P450.
atom of Compound I depends on the redox potential of the porphyrin
macrocycles. With the same axial ligand and similar sterics of aryl ring
meso substituents, the reactivities of Compound I models with
electron-deficient porphyrins were greater than the reactivities of
those with electron-rich porphyrin rings [23–25].
In a study of oxidations by oxoiron(IV) porphyrins, our group
proposed a disproportionation step in the reaction mechanism where
the oxoiron(IV) species disproportionates to give an iron(III) species
and a more reactive oxoiron(IV) porphyrin radical cation that is the
true oxidant [26]. This conclusion was based on inverted reactivity
patterns in regard to the electron demand of the porphyrin ring.
Supporting evidence for a disproportionation step included dual-
parameter Hammett analyses and the observation of suppressed
reactivity with the addition of excess iron(III) species. Herein we
report direct spectroscopic observation of conversion of oxoiron(IV)
species to the corresponding iron(IV)–oxo porphyrin radical cation in
a mixed solution of acetonitrile and water (1:1, v/v). The results
support the conclusion that oxoiron(IV) species react by initial
disproportionation to give oxoiron(IV) porphyrin radical cations
that are true oxidants.
Three porphyrin systems, 5,10,15,20-tetrakis(2,6-dichlorophenyl)
porphyrin (TDCPP), 5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin
(TDFPP) and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin
(TPFPP), were studied in this work (Scheme 1). The commercially
available free porphyrin ligands with chloride counterions were
converted to the iron(III) hydroxide complexes (porphyrin)FeIII(OH)
(1), which were then oxidized to oxoiron(IV) porphyrin species (2)
according to literature methods [15]. Two equivalents of the terminal
oxidant m-chloroperoxybenzoic acid (m-CPBA) were found to be
necessary for the complete formation of 2 in acetonitrile solution
Electronic effects were found to be important factors in controlling
the reactivity of high-valent oxoiron species. For example, it was
demonstrated that the axial ligands on iron significantly affected the
reactivity of Compound I analogs in oxygenation reactions [19–21].
For a series of oxoiron(IV) tetraarylporphyrin radical cations prepared
by Fujii [22], the effects of the aryl ring meso substituents on electronic
structures and reactivities revealed that the reactivity of the oxygen
⁎
Corresponding authors. Tel.: +1 312 413 2106; fax: +1 312 996 0431.
E-mail addresses: z-pan@northwestern.edu (Z. Pan), men@uic.edu (M. Newcomb).
Present address: Department of Chemistry, Northwestern University, Evanston, IL
1
60208, USA.
1387-7003/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2011.03.044

Z. Pan, M. Newcomb / Inorganic Chemistry Communications 14 (2011) 968–970
969
Ar
Ar
O
FeIV
N
Ar
X-
Ar
O
N
N
OHN
FeIII
N
N
N
N
N
N
N
FeIV
N
6 equiv. m-CPBA
acid catalyst
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
1a, 2a, 3a: Ar = 2,6-dichlorophenyl
1b, 2b, 3b: Ar = 2,6-difluorophenyl
1c, 2c, 3c: Ar = pentafluorophenyl
Scheme 1. A reaction scheme for the oxidation of (porphyrin)FeIII(OH) (1) and acid-catalyzed conversion of oxoiron(IV) porphyrin species (2) to oxoiron(IV) porphyrin radical
cations (3).
for all three porphyrin systems as determined by UV–visible
spectroscopy [15,26].
yield (N95%). The overall reaction sequence is consistent for the
behavior expected for oxoiron(IV) porphyrin radical cation species.
Conversion from (TDCPP)FeIV(O) (2a) to (TDCPP)+.FeIV(O)(X)
(3a) was shown not to be due to direct reaction of 2a with excess m-
CPBA. A solution of 2a prepared in acetonitrile using six equivalents of
m-CPBA was stable, but addition of excess acid m-chlorobenzoic acid
(m-CBA) resulted in complete conversion of 2a to 3a with a second-
order rate constant of (1.3 0.2)×102 M−1 s−1 (inset of Fig. 1). This
result demonstrated that acid could catalyze the disproportionation
reaction of the Compound II model 2a to the Compound I model 3a in
the presence of six equivalents of m-CPBA. With smaller amounts of
oxidant, such as two equivalents of m-CPBA used in the preparation of
2a before addition of m-CBA, incomplete transformation to 3a was
observed. Apparently, slow disproportionation occurs in the absence
of acid catalysis, and the oxidant is degraded by reaction with solvent.
Similar experiments were conducted with the other two
porphyrin systems 2b and 2c generated with six equivalents of m-
CPBA. Addition of m-CBA (up to 5 mM) to the corresponding CH3CN/
H2O (1:1, v/v) solution of oxoiron(IV) porphyrin species 2b and 2c
(2×10− 5 M) at ambient temperature was studied. As shown by the
UV–visible spectrum in Fig. 2, (TDFPP)FeIV(O) (2b) was not fully
converted to the corresponding oxoiron(IV) porphyrin radical cation
(TDFPP)+.FeIV(O) (3b). In addition to the absorbance at 551 nm from
2b [15], a characteristic Q-band at 550–750 nm for Compound I
analog 3b [19] was observed together with broad Soret band. The
UV–visible spectrum of most electron-deficient system, TPFPP (3b)
did not reveal any detectable amount of conversion of 2c to 3c upon
the addition of excess m-CBA.
Attempts to prepare (TDCPP)+.FeIV(O)(X) (3a) at room temper-
ature by adding an excess of m-CPBA (2–100 equivalents) to ferric
species 1a were not successful in either CH2Cl2 or CH3CN solutions.
Addition of two equivalents of m-CPBA to the CH2Cl2 solution of 1a
led to axial ligand exchange and formation of a high-spin (TDCPP)
FeIII(m-CPBA) (417, 509 and 573 nm) [27]. In acetonitrile, addition
of the same amount m-CPBA to 1a generated red species (TDCPP)
FeIV(O) (2a), which slowly decayed to a mixture of 1a and (TDCPP)
FeIII(m-CBA) (414, 505 and 577 nm). A large excess of m-CPBA (100
equivalents) could prolong the life-time of 2a because of the
regeneration of 2a from ferric porphyrin, but no oxoiron(IV)
porphyrin radical cation species was observed.
It was known that water can substantially stabilize oxoiron(IV)
porphyrin radical cation species [19]. When a mixed solvent of
acetonitrile and water (1:1, v/v) was used, the UV–visible spectra of
1a and 2a were the same as those in pure acetonitrile solution as
expected for the OH ligation of ferric porphyrin 1a and the neutral
character of oxoiron(IV) porphyrin species 2a. Addition of 100
equivalents m-CPBA to either 1a or 2a resulted in formation of a
new green species that showed a weak Soret band at 390 nm and a
broad Q-band at 550–750 nm (Fig. 1) in addition to partial porphyrin
degradation. The UV–visible spectrum of the green species was
characteristic for oxoiron(IV) porphyrin radical cation and very
similar to the reported Compound I spectra of several (TDCPP)+.FeIV
(O)(X) (3a) species generated by oxidizing ferric porphyrins contain-
ing weak axial ligands at low temperature [9,22,28]. When excess
amounts of organic reductants such as styrene or diphenylmethane
were added to above solutions of 3a, the UV–visible spectrum
returned to that of ferric porphyrin 1a, which was recovered in high
The diverse results for the three oxoiron(IV) porphyrin species 2
upon the addition of m-CBA can be explained by the different
disproportionation equilibrium constants Kdis for the three porphyrin
0.7
2.0
1.5
1.0
0.45
0.40
0.6
0.5
0.4
0.3
0.2
0.1
0.0
418 nm
0.35
0.30
0.25
0.20
0.15
0.10
0.05
390 nm
1.0
1.5
2.0
2.5
3.0
x 5
[m-CBA] (mM)
0.5
675 nm
700
558 nm
0.0
300
300
400
500
600
800
400
500
600
700
800
Wavelength (nm)
Wavelength (nm)
Fig. 1. Conversion of (TDCPP)FeIV(O) (2a) to (TDCPP)+.FeIV(O)(X) (3a) by excessive m-
CBA in CH3CN/H2O (1:1, v/v). Inset: observed rate constants at 675 nm.
Fig. 2. UV–visible spectra of (TDFPP)FeIV(O) (2b) before (dashed line) and after (solid
line) the addition of excessive amount of m-CBA in CH3CN/H2O (1:1, v/v) solution.

970
Z. Pan, M. Newcomb / Inorganic Chemistry Communications 14 (2011) 968–970
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2 (TDCPP)FeIV(O) + H+
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2c
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3c
Scheme 2. Different disproportionation equilibrium constants Kdis in three porphyrin
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NMR experiments, the rate of the disproportionation reaction would be
increased such that the lifetime of 2 decreased significantly from several
hours in theUV–visible spectral studies toa few minutes in NMR studies.
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Acknowledgments
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