Kinetics and mechanism of oxidation reactions of porphyrin-iron(IV)-oxo intermediates

Article abstract of DOI:10.1021/ic700395j

The kinetics of the reactions of three porphyrin-iron(IV)-oxo derivatives with alkenes and benzylic alcohols were measured. The iron-oxo systems studied were 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin-iron(IV)-oxo (2a), 5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin-iron(IV)-oxo (2b), and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin-iron(IV)-oxo (2c). Species 2 were stable for hours at room temperature as dilute solutions in acetonitrile and reacted hundreds to thousands of times faster in the presence of high concentrations of substrates. Typical second-order rate constants determined from pseudo-first-order kinetic studies are 1-2 × 10^-2 M ^-1 s^-1 for reactions with styrene and 3 × 10 ^-2 M^-1 s^-1 for reactions with benzyl alcohol. The reactivity order for the iron-oxo species was 2a > 2b > 2c, which is inverted from that expected on the basis of the electron demand of the porphyrin macrocycles, and the oxidation reaction was suppressed when excess porphyrin-iron(lll) complex was added to reaction mixtures. These observations indicate that the reactions involve disproportionation of the iron(IV)-oxo species 2 to give an iron(III) species and a more highly oxidized iron species, presumed to be an iron(IV)-oxo porphyrin radical cation, that is the true oxidant in the reactions. Analyses of the kinetics of oxidations of a series of para-substituted benzylic alcohols with Hammett σ^--substituent constants and with a dual-parameter method developed by Jiang (Jiang, X. K. Acc. Chem. Res. 1997, 30, 283) indicated that considerable positive charge developed on the benzylic carbons in the oxidation reactions, as expected for electrophilic oxidants, and also that substantial radical character developed on the benzyl carbon in the transition states.

Full text of DOI:10.1021/ic700395j

Inorg. Chem. 2007, 46, 6767−6774
Kinetics and Mechanism of Oxidation Reactions of
Porphyrin Iron(IV) Oxo Intermediates
−
−
Zhengzheng Pan and Martin Newcomb*
Department of Chemistry, UniVersity of Illinois at Chicago, 845 W. Taylor Street,
Chicago, Illinois 60607
Received March 1, 2007
The kinetics of the reactions of three porphyrin
measured. The iron oxo systems studied were 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin
5,10,15,20-tetrakis(2,6-difluorophenyl)porphyrin iron(IV) oxo (2b), and 5,10,15,20-tetrakis(pentafluorophenyl)por-
phyrin iron(IV) oxo (2c). Species 2 were stable for hours at room temperature as dilute solutions in acetonitrile
and reacted hundreds to thousands of times faster in the presence of high concentrations of substrates. Typical
second-order rate constants determined from pseudo-first-order kinetic studies are 1
10-2 M-1 s-1 for reactions
10- M- s- for reactions with benzyl alcohol. The reactivity order for the iron
oxo species
was 2a > 2b > 2c, which is inverted from that expected on the basis of the electron demand of the porphyrin
macrocycles, and the oxidation reaction was suppressed when excess porphyrin iron(III) complex was added to
−iron(IV)−oxo derivatives with alkenes and benzylic alcohols were
−
−
iron(IV) oxo (2a),
−
−
−
−
−
−2 ×
2
1
1
with styrene and 3
×
−
−
reaction mixtures. These observations indicate that the reactions involve disproportionation of the iron(IV)
−
oxo
oxo
species 2 to give an iron(III) species and a more highly oxidized iron species, presumed to be an iron(IV)
−
porphyrin radical cation, that is the true oxidant in the reactions. Analyses of the kinetics of oxidations of a series
of para-substituted benzylic alcohols with Hammett
+-substituent constants and with a dual-parameter method
σ
developed by Jiang (Jiang, X. K. Acc. Chem. Res. 1997, 30, 283) indicated that considerable positive charge
developed on the benzylic carbons in the oxidation reactions, as expected for electrophilic oxidants, and also that
substantial radical character developed on the benzyl carbon in the transition states.
High-valent porphyrin-iron-oxo derivatives are thought
to be the active oxidants in heme-containing peroxidase,
catalase, and cytochrome P450 enzymes,1-4 and porphyrin-
iron complexes are among the better-known laboratory
catalysts.5,6 In catalytic processes, porphyrin-iron(III) species
are oxidized by sacrificial oxidants such as m-chloroperoxy-
benzoic acid (MCPBA) or iodosobenzene (PhIO). Depending
on the identity of the porphyrin, solvents, and reaction
conditions, either porphyrin-iron(IV)-oxo or iron(IV)-oxo
porphyrin radical cations can be detected in these reactions,
and both are generally thought to be active oxidants. In
biological contexts, iron(IV)-oxo porphyrin radical cations
are commonly referred to as compound I species. Compound
I species are detected in peroxidase enzymes and are thought
to be the active species for many difficult oxidation reactions
effected by cytochrome P450 enzymes including hydroxyl-
ations of saturated C-H positions.7 The one-electron-reduced
product of compound I, a porphyrin-iron(IV)-oxo inter-
mediate commonly called compound II in reference to heme-
containing enzymes, also acts as an oxidant of reactive
species such as ascorbate, which is oxidized in a one-
electron-transfer oxidation reaction.2,3
Although compound I and compound II species in per-
oxidase and catalase enzymes and porphyrin-iron(IV)-oxo
models have been known for decades, the detailed mecha-
nisms of porphyrin-iron(IV)-oxo reactions are elusive,
especially for model compounds reacting in two-electron,
oxo-transfer oxidation reactions. For example, electron-
* To whom correspondence should be addressed. E-mail: men@uic.edu.
(1) Cytochrome P450 Structure, Mechanism, and Biochemistry, 3rd ed.;
Ortiz de Montellano, P. R., Ed.; Kluwer: New York, 2005.
(2) Dawson, J. H. Science 1988, 240, 433-439.
(3) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. ReV.
1996, 96, 2841-2887.
(4) Denisov, I. G.; Makris, T. M.; Sligar, S. G.; Schlichting, I. Chem.
ReV. 2005, 105, 2253-2277.
(5) Metalloprophyrins in Catalytic Oxidations; Sheldon, R. A. Ed.; Marcel
Dekker: New York, 1994.
(7) Makris, T. M.; von Koenig, K.; Schlichting, I.; Sligar, S. G. J. Inorg.
Biochem. 2006, 100, 507-518.
(6) Meunier, B. Chem. ReV. 1992, 92, 1411-1456.
10.1021/ic700395j CCC: $37.00
Published on Web 07/14/2007
© 2007 American Chemical Society
Inorganic Chemistry, Vol. 46, No. 16, 2007 6767

Pan and Newcomb
Table 1. Spectral Properties of Iron Species 1 and Iron(IV)-Oxo
Complexes 2a
withdrawing substituents in the aromatic rings of tetra-aryl-
substituted porphyrins are expected to activate an iron-oxo
derivative,8 in which case 5,10,15,20-tetrakis(pentafluoro-
phenyl)porphyrin-iron(IV)-oxo, (TPFPP)FeIV(O), should be
more reactive than 5,10,15,20-tetramesitylporphyrin-
iron(IV)-oxo, (TMP)FeIV(O). The oxidation potentials for
(TPFPP)FeIV(O) and (TMP)FeIV(O) are in agreement with
predictions based on the electron-withdrawing effects of the
aryl substituents,9,10 but the reactivities of the iron(IV)-oxo
species as oxidants are not. (TPFPP)FeIV(O) epoxidizes
alkenes slowly,11 but (TMP)FeIV(O) apparently reacts 1-2
orders of magnitude more rapidly with styrene.12 Moreover,
in polar solvents, (TMP)FeIV(O) appeared to react by a
disproportionation pathway to give a reactive species in the
formal oxidation state of iron(V).12 The apparent inverted
reactivity pattern for porphyrin-iron(IV)-oxo species and
possible disproportionation mechanisms for their reactions
are reminiscent of oxidations by porphyrin-manganese(IV)-
oxo species13,14 and porphyrin-chromium(IV)-oxo species15
that display similar kinetic behavior and/or disproportionate
to give reactive porphyrin-metal(V)-oxo species.
Much of the mechanistic uncertainty regarding porphyrin-
metal-oxo species is due to the limited number of kinetic
studies of these species.6,16 Our group previously reported
the kinetics of reactions of high-valent porphyrin-metal-
oxo species14,17-19 and a heme-thiolate enzyme compound
I derivative20 with several organic reductants to establish a
catalog of reactivities of these species for mechanistic
analyses. In this work, we report rate constants for the
reactions of three porphyrin-iron(IV)-oxo complexes with
alkenes and alcohols in an acetonitrile solvent. Inverted
reactivity patterns were found, with the porphyrin-iron(IV)-
oxo species that would be predicted to be most reactive on
the basis of electronic effects being the least reactive. The
reaction mechanisms appear to predominantly involve dis-
proportionation reactions that give iron(III) species and active
oxidants that are assumed to be iron(IV)-oxo porphyrin
radical cations.
Soret λmax
(nm)
Q band λmax
δpyrrole
porphyrin-iron
(nm)
(ppm)b
1a, (TDCPP)FeIII(OH)
1b, (TDFPP)FeIII(OH)
1c, (TPFPP)FeIII(OH)
(TMP)FeIII(OH)c
412
405
402
418
418
412
411
418
573
567
564
580
558
551
547
540
105.8
104.0
105.2
116.4
5.9
2a, (TDCPP)FeIV(O)
2b, (TDFPP)FeIV(O)
2c, (TPFPP)FeIV(O)
(TMP)FeIV(O)c
4.1
4.3
8.4
a UV-vis spectra in CH3CN at room temperature, and NMR spectra in
CD3CN at -35 °C unless noted. b Chemical shift of pyrrole protons
downfield from TMS. c (TMP) ) 5,10,15,20-tetrakis(2,4,6-trimethylphen-
yl)porphyrinato. UV-vis spectrum in CH2Cl2 from ref 12. NMR spectrum
in toluene-d8 from ref 25.
Experimental Section
Materials. Free ligands 5,10,15,20-tetrakis(2,6-dichlorophenyl)-
porphyrin (TDCPP)H2, 5,10,15,20-tetrakis(2,6-difluorophenyl)por-
phyrin (TDFPP)H2, and 5,10,15,20-tetrakis(pentafluorophenyl)-
porphyrin (TPFPP)H2 were purchased from FrontierSci, Inc. and
used as supplied. Iron(III) hydroxy complexes (TDCPP)FeIII(OH)
(1a), (TDFPP)FeIII(OH) (1b), and (TPFPP)FeIII(OH) (1c) were
prepared by literature methods.21-23 Commercial HPLC-grade
acetonitrile (99.9%) was distilled from P2O5 prior to use. Com-
mercial m-chloroperoxybenzoic acid (MCPBA) (77%) was purified
by crystallization from CH2Cl2 and dried in vacuo. All reactive
substrates for kinetic studies were commercial materials of the
highest available purity and were passed through a column of dry,
active alumina (grade I) before use.
Instrumentation. The UV-vis spectra were recorded on an
Agilent 8453 diode-array spectrophotometer, which was equipped
with an Applied Photophysics RX2000 rapid mixing accessory for
1
studying fast reactions. H NMR spectra were recorded on a 500
MHz instrument; chemical shifts are reported in ppm relative to
an internal TMS standard. The EPR spectra were obtained at 77
K.
Preparation of Porphyrin-Iron(IV)-Oxo Derivatives 2.
Ferric porphyrin hydroxyl complexes 1 were used as the precursors
of 2. When 2-4 equiv of MCPBA was added to an acetonitrile
solution of 1 (20 µM), the solution changed color from light red to
dark red. The Soret bands were red-shifted in all cases, and the Q
bands indicated a change from ferric hydroxides to ferryl-oxo
complexes 2. UV-vis spectral details are listed in Table 1. In dilute
solutions, complexes 2 were stable for hours at ambient temperature
(kobs < 1 × 10-4 s-1). Higher concentration solutions were used
for 1H NMR spectra (5 mM), and the pyrrole proton chemical shifts
are listed in Table 1. The more concentrated NMR samples were
less stable than the dilute solutions used for UV-vis spectroscopy.
The NMR samples were prepared at and the spectra were recorded
at ca. -40 °C, and when these samples were warmed to room
temperature, the solutions quickly changed color to green/brown.
(8) Dolphin, D.; Traylor, T. G.; Xie, L. Y. Acc. Chem. Res. 1997, 30,
251-259.
(9) Lee, W. A.; Calderwood, T. S.; Bruice, T. C. Proc. Natl. Acad. Sci.
U.S.A. 1985, 82, 4301-4305.
(10) Lim, M. H.; Lee, Y. J.; Goh, Y. M.; Nam, W.; Kim, C. Bull. Chem.
Soc. Jpn. 1999, 72, 707-713.
(11) Nam, W.; Park, S. E.; Lim, I. K.; Lim, M. H.; Hong, J. K.; Kim, J. J.
Am. Chem. Soc. 2003, 125, 14674-14675.
(12) Groves, J. T.; Gross, Z.; Stern, M. K. Inorg. Chem. 1994, 33, 5065-
5072.
(13) Groves, J. T.; Stern, M. K. J. Am. Chem. Soc. 1988, 110, 8628-
8638.
(14) Zhang, R.; Horner, J. H.; Newcomb, M. J. Am. Chem. Soc. 2005,
127, 6573-6582.
(15) Groves, J. T.; Kruper, W. J., Jr.; Haushalter, R. C.; Butler, W. M.
Inorg. Chem. 1982, 21, 1363-1368.
(16) Nam, W. Acc. Chem. Res. [Online early access]. DOI: 10.1021/
ar700027f. Published Online: May 01, 2007.
(17) Zhang, R.; Newcomb, M. J. Am. Chem. Soc. 2003, 125, 12418-12419.
(18) Pan, Z.; Zhang, R.; Newcomb, M. J. Inorg. Biochem. 2006, 100, 524-
532.
(19) Pan, Z.; Zhang, R.; Fung, L. W.-M.; Newcomb, M. Inorg. Chem. 2007,
46, 1517-1519.
(20) Zhang, R.; Nagraj, N.; Lansakara-P., D. S. P.; Hager, L. P.; Newcomb,
M. Org. Lett. 2006, 8, 2731-2734.
1
Upon subsequent cooling to ca. -35 °C, the H NMR spectrum
indicated the formation of ferric high-spin complexes (δpyrrole> 100
ppm).
Kinetic Studies of Reactions of Porphyrin-Iron(IV)-Oxo
Species 2 with Organic Substrates. In a typical reaction, solutions
(21) Adler, A. D.; Longo, F. R.; Kampas, F.; Kim, J. J. Inorg. Nucl. Chem.
1970, 32, 2443-2445.
(22) Cheng, R. J.; Latos-Grazynski, L.; Balch, A. L. Inorg. Chem. 1982,
21, 2412-2418.
(23) Woon, T. C.; Shirazi, A.; Bruice, T. C. Inorg. Chem. 1986, 25, 3845-
3846.
6768 Inorganic Chemistry, Vol. 46, No. 16, 2007

Porphyrin-Iron(IV)-Oxo Intermediates
Scheme 1
of 2 (20 µM in CH3CN) and an organic substrate with the desired
concentration in CH3CN were loaded into two gastight syringes.
The samples were mixed in a UV-vis flow cell, and the data was
collected with delay times as short as 0.3 s. The decay rates for 2
and the formation rates for the ferric porphyrin products were
measured at λmax of the Q-band signals. The decay and growth traces
were fit to single-exponential solutions, and second-order rate
constants were obtained from the pseudo-first-order rate constants
via eq 1 in the text.
Single-Turnover Product Studies. Solutions of the 2a (20 µM)
in CH3CN were prepared as above. To these were added either
benzyl alcohol or styrene such that the final substrate concentration
was 0.10 M. The mixtures were stirred for 1-2 h. The samples
were filtered through an alumina column to remove the porphyrin
complex and analyzed by GC. Benzaldehyde and styrene oxide were
identified by GC co-injection with authentic samples. The yields
of products were determined relative to substrate using predeter-
mined response factors. Control reactions using MCPBA in the
absence of the porphyrin complex 1a gave only traces (<3% based
on oxidant) of the oxidation products.
Figure 1. (A) Time-resolved UV-vis spectrum for the conversion of 1a
(10 µM) to 2a in CH3CN by reaction with 2 equiv of MCPBA. The initial
trace was recorded at 0.3 s after mixing, and subsequent traces were recorded
at 8 s intervals. (B) Time-resolved spectrum for the reaction of 2a with 0.4
M styrene; the inset shows the kinetic traces at 558 and 573 nm.
not convoluted into any of our kinetic values reported below.
The absence of MCPBA in solutions of 2 was apparent from
the kinetic studies, where clean exponential behavior was
observed with no lag time at the beginning of the reactions
(e.g., Figure 1B). If excess MCPBA remained, a lag in the
exponential decay and growth curves would be observed
during the period when the excess MCPBA was being
consumed. For example, the formation of 2a in the reaction
shown in Figure 1A had a half-life of ca. 30 s, whereas the
reaction of 2a with styrene shown in Figure 1B had a half-
life of ca. 150 s. Because the oxidation of 1a to 2a was faster
than the reaction of 2a with a substrate under these
conditions, the presence of excess MCPBA in the reaction
medium would result in a flat signal at the outset of the
reaction of 2a, which would continue until the excess
MCPBA was depleted.
In balanced oxidation reactions of complexes 1 to give
iron(IV)-oxo complexes 2, only 0.5 equiv of MCPBA
should be required, but reactions of the porphyrin-iron(III)
species with 0.5 or even 1 equiv of MCPBA did not convert
the iron(III) complex completely to the iron(IV)-oxo deriva-
tive. Our reactions required 2-4 equiv of MCPBA to
complete the oxidations; previously, Nam et al. reported that
4 equiv of MCPBA were required for the complete conver-
sion of (TPFPP)FeIIICl to the oxo complex 2c.11 The excess
MCPBA apparently is consumed when highly reactive iron-
oxo transients react with the solvent, presumably forming
formaldehyde cyanohydrin. Species 2 are the relatively
unreactive sinks. In any event, once prepared, dilute solutions
of porphyrin-iron(IV)-oxo species 2 in acetonitrile were
stable for hours.
Results and Discussion
The systems studied are shown in Scheme 1. The com-
mercial porphyrin ligands (TDCPP)H2, (TDFPP)H2, and
(TPFPP)H2 were converted to the iron(III) hydroxide com-
plexes (porph)FeIII(OH) (1) by literature methods.21-23 We
employed hydroxide complexes in this work so that ligand-
exchange reactions with water would not result in new
species and because the hydroxide complexes are easier to
oxidize than the corresponding chloride complexes.
Oxidation of complexes 1 with purified MCPBA in
acetonitrile gave the iron(IV)-oxo complexes 2 as indicated
qualitatively by a color change from light red to deep red.
In the UV-vis spectra of complexes 2, the Soret bands were
red-shifted from those of 1, and the Q bands were distinct.
Figure 1A shows the time-resolved spectrum of 1a as it is
oxidized to 2a, which is typical. The spectra of 1b, 2b, 1c,
and 2c are in the Supporting Information. The hydroxide
complex 1a was fully oxidized to species 2a with ap-
proximately 2 equiv of MCPBA at the concentrations used
in UV-vis spectroscopic studies, but complexes 2b and 2c
required approximately 4 equiv of MCPBA. For solutions
that were 10 µM in iron species in acetonitrile solvent, the
approximate half-lives for the formation of 2 from reactions
of 1 were 1-10 s.
It is important to note that excess MCPBA was employed
to oxidize the ferric complexes 1 to the iron(IV)-oxo species
2, but no excess MCPBA remained in the solutions contain-
ing species 2. Thus, the kinetics of reactions of MCPBA are
The production of porphyrin-iron(IV)-oxo species 2
instead of more highly oxidized iron(IV)-oxo porphyrin
Inorganic Chemistry, Vol. 46, No. 16, 2007 6769

Pan and Newcomb
radical cations under the reaction conditions we used is
noteworthy. In the present study with an acetonitrile solvent,
species 2 are formed, but MCPBA oxidations of porphyrin-
iron(III) species in acetonitrile-water mixtures give the more
highly oxidized species.18 The origin of the water-stabilizing
effect is not understood at the molecular level, but a similar
phenomenon is known for the porphyrin-manganese-oxo
species.14
Our studies do not address directly the mechanisms of the
formation of species 2. We assume that two-electron oxida-
tions with oxo transfer from MCPBA to species 1 give
transients with a formal oxidation state of +5 on iron, and
these species react with the solvent in competition with the
comproportionation reactions with another molecule of 1 to
give two molecules of iron(IV)-oxo species 2. Such a
pathway provides rationalizations for the excess MCPBA
required to drive the reaction to completion and the formation
of more highly oxidized iron-oxo species in acetonitrile-
water mixtures. Alternatively, homolytic cleavage of an
iron(III)-acyl peroxide complex can give an iron(IV)-oxo
species directly.24
The iron(IV)-oxo species 2 were characterized by UV-
vis, EPR, and NMR spectroscopies. The UV-vis spectrum
of each species 2 (Figure 1 and Supporting Information)
displayed a Soret band that was sharper, more intense, and
red-shifted from that of the corresponding iron(III) species
1. The Q bands of the iron(IV)-oxo species 2 were distinct
from those of the iron(III) species, and no peaks were
observed at ca. 650 nm, the region at which the Q bands of
iron(IV)-oxo porphyrin radical cations absorb. In EPR
studies, complexes 2 were silent, as expected for an iron(IV)
species (S ) 1).
Figure 2. (A) 1H NMR spectrum of 2c in CD3CN at -35 °C. The pyrrole
protons of 2c absorb at δ 4.3. Other signals in the spectrum are from TMS
(δ 0), CHD2CN (δ 2), and m-chlorobenzoic acid and/or MCPBA (δ 7-8
and 9.5). (B) Curie plot for chemical shifts of the pyrrole protons in 2c as
a function of temperature between 5 and -45 °C.
Differences in the stabilities of high-concentration samples
(ca. 5 mM for NMR studies) and low-concentration samples
(ca. 20 µM for UV-vis spectra) have been noted before.27
High conversion ratios of 1 to 2 at the concentrations needed
for NMR spectra required a large excess of MCPBA and
low reaction temperatures (ca. -35 °C). Even with those
conditions, the formation of 2a and 2b was not complete,
although new signals for the pyrrole protons of 2 could be
detected. In contrast, the dilute samples of 2 in CH3CN used
for UV-vis spectroscopy were prepared at room temperature
and were stable for hours. In the discussion below, we reason
that the iron(IV)-oxo derivatives 2 disproportionate and that
the active oxidant in the systems studied here are actually
iron(IV)-oxo porphyrin radical cations. In such a case, a
concentration-dependent decay of species 2 would be
observed when the disproportionation reactions were fully
or partially rate limiting, but an accelerated decay is not
required if the disproportionation-comproportionation reac-
tions are fast relative to the oxidations. We speculate that
the accelerated decay of species 2 in the high-concentration
NMR samples reflects the increased velocities for the
oxidations of the porphyrin macrocycles in competition with
the oxidation of solvent molecules, which must be concen-
tration-dependent.
1
The H NMR spectra of complexes 1 and 2 in CD3CN
solutions showed broad peaks for the macrocycle pyrrole
protons that were highly characteristic, with absorbances at
ca. 105 ppm for the iron(III) complexes 1 and ca. 5 ppm for
the iron(IV)-oxo species 2. The large shift for the pyrrole
protons in species 1 (δ > 100 ppm) is consistent with that
of high-spin ferric complexes. The chemical shifts of the
pyrrole protons in iron(IV)-oxo complexes 2 suggest six-
coordinate iron species;25 we assume that the sixth coordina-
tion site is occupied by acetonitrile. Some of the spectral
properties of species 1 and iron(IV)-oxo species 2 are listed
in Table 1. For comparison, the spectral properties of the
well-studied analogous iron-(TMP) complexes12,22,25 also are
listed.
Figure 2A shows the NMR spectrum of 2c, which is the
cleanest NMR spectrum we obtained; the signals for MCPBA
and m-chlorobenzoic acid, which overlap, were observed in
the absence of the iron species. A Curie plot for the pyrrole
protons in 2c (Figure 2B) is similar to those for other iron(IV)
species and confirms the paramagnetic character of 2c.25,26
The primary objective of this work was to make kinetic
studies of the reactions of the iron(IV)-oxo species. At the
low concentrations used in the UV-vis spectroscopy studies,
species 2 were relatively stable. For example, the rate
constant for the first-order decay of a 10 µM solution of 2a
(24) Yamaguchi, K.; Watanabe, Y.; Morishima, I. J. Am. Chem. Soc. 1993,
115, 4058-4065.
(25) Balch, A. L.; Chan, Y. W.; Cheng, R. J.; La Mar, G. N.; Latos-
Grazynski, L.; Renner, M. W. J. Am. Chem. Soc. 1984, 106, 7779-
7785.
(26) Groves, J. T.; Quinn, R.; McMurry, T. J.; Nakamura, M.; Lang, G.;
Boso, B. J. Am. Chem. Soc. 1985, 107, 354-360.
(27) Bell, S. E. J.; Cooke, P. R.; Inchley, P.; Leanord, D. R.; Lindsay Smith,
J. R.; Robbins, A. J. Chem. Soc., Perkin Trans. 1991, 2, 549-559.
6770 Inorganic Chemistry, Vol. 46, No. 16, 2007

Porphyrin-Iron(IV)-Oxo Intermediates
Table 2. Apparent Second-Order Rate Constants for Reactions of
Porphyrin-Iron(IV)-Oxo Species 2 in Acetonitrilea
100 × kox (M-1 s-1
)
substrate
(TDCPP)FeIV(O) (TDFPP)FeIV(O) (TPFPP)FeIV(O)
1-phenylethanol
diphenylmethanol
benzyl alcohol
benzyl alcohol-d7
4-chlorobenzyl
alcohol
21.3 ( 1.8
16.7 ( 1.1
3.3 ( 0.2
0.64 ( 0.08
6.7 ( 0.2
12.7 ( 0.8
10.8 ( 0.4
3.0 ( 0.1
0.66 ( 0.02
5.7 ( 0.2
7.7 ( 1.1
4.9 ( 0.2
3.0 ( 0.1
0.53 ( 0.01
4.2 ( 0.2
4-fluorobenzyl
alcohol
4-methylbenzyl
alcohol
4-methoxybenzyl
alcohol
cis-cyclooctene
cyclohexene
cis-stilbene
7.2 ( 0.3
28.0 ( 1.3
168 ( 8
6.5 ( 0.4
18.0 ( 1.3
124 ( 4
5.3 ( 0.3
17.1 ( 0.9
90 ( 6
9.8 ( 0.2
7.3 ( 0.1
4.2 ( 0.3
1.9 ( 0.1
7.4 ( 0.4
ndb
1.8c
ndb
6.0c
4.1 ( 0.1
1.6 ( 0.1
5.1 ( 0.6
2.1 ( 0.1
0.9 ( 0.1
3.5 ( 0.1
styrene
4-methylstyrene
a Apparent second-order rate constants for reactions at 22 ( 2 °C. The
values are averages of two or three runs, and the stated errors are 2σ. b Not
determined. c Rate constant estimated from results in ref 11.
m-chlorobenzoate complexes, which have distinct UV-vis
spectra.28 Furthermore, the UV-vis spectra of the products
excluded iron(II) species.29
Figure 3. Kinetic results. (A) Kinetic traces at 418 nm for the reactions
of iron(IV)-oxo species 2a in CH3CN with (from the top) 0.0, 0.2, 0.4,
0.7, and 1.0 M styrene. The inset shows a plot of the data according to eq
1. (B) Observed rate constants for the reactions of diphenylmethanol with
2a (O), 2b (0), and 2c (4).
Figure 3A shows kinetic traces at 418 nm for reactions of
2a with different concentrations of styrene. The traces were
well fit to single-exponential decay, as expected for reactions
under pseudo-first-order conditions. The results were ana-
lyzed with eq 1, where kobs is the observed rate constant, k0
is a background rate constant for decay, kox is the second-
order rate constant for reaction of the iron(IV)-oxo species
with substrate, and [Sub] is the concentration of substrate.
The inset in Figure 3A shows the plot according to eq 1,
where the slope of the line is the second-order rate constant
kox. Figure 3B shows the data for reactions of iron(IV)-oxo
species 2 with diphenylmethanol, and Figure S3 in the
Supporting Information shows the data for reactions with
1-phenylethanol. Apparent second-order rate constants for
reactions of iron(IV)-oxo species 2 with several substrates
are listed in Table 2. With little exception, the apparent order
of reactivity of the iron-oxo species with a given substrate
was 2a > 2b > 2c.
used for UV-vis spectroscopy was k ≈ 1 × 10-4 s-1.
Qualitatively, the order of reactivity for the decay in CH3CN
solutions was 2a > 2b > 2c, which presages the inverted
reactivity order observed with organic reductants.
We studied the reactions of iron-oxo complexes 2 with
alkenes and with alcohols using UV-vis spectroscopy with
low concentrations of iron species. Under turnover conditions
with porphyrin-iron(III) species as catalysts and MCPBA
or other sacrificial oxidants, epoxides and carbonyl com-
pounds, respectively, are the major products formed from
these substrates.6 We performed cursory product studies for
the apparent “stoichiometric” reactions of the iron(IV)-oxo
species 2a. Thus, solutions of 2a (20 µM) in CH3CN were
allowed to react with 5000-fold excesses of benzyl alcohol
and styrene, and the reaction mixtures were analyzed by GC.
Under these single-turnover conditions, the major product
formed from benzyl alcohol was benzaldehyde (70%), and
the major product formed from styrene was styrene oxide
(60%), where the yields were calculated based on a stoichi-
ometry of 2 equiv of 2a reacting with 1 equiv of the organic
substrate.
The kinetic studies employed large excesses of substrates
so that all decay reactions of iron(IV)-oxo species were
pseudo-first-order. The results in Figure 1B and Figure 3A
are typical. The time-resolved spectrum in Figure 1B shows
the clean conversion of iron(IV)-oxo 2a to 1a as it reacts
with styrene, and the isosbestic points observed at 442, 529,
and 567 nm indicate that no other porphyrin-iron intermedi-
ate accumulated to detectable levels during the reaction. We
specifically note that the iron-containing products were
hydroxide complexes 1 and not the porphyrin-iron(III)
kobs ) k0 + kox[Sub]
(1)
Under the conditions we employed, the concentrations of
substrates were thousands of times as large as those of the
oxo complexes. Therefore, the concentration of product
formed in the initial substrate oxidation was much smaller
than the concentration of substrate, and secondary oxidations
were not an issue. The single-exponential data fits confirm
that the initial oxidation reactions were the major reaction
pathways. If secondary oxidations were important, the decay
traces would not show pseudo-first-order behavior, and the
(28) Machii, K.; Watanabe, Y.; Morishima, I. J. Am. Chem. Soc. 1995,
117, 6691-6697.
(29) Ghiladi, R. A.; Kretzer, R. M.; Guzei, I.; Rheingold, A. L.; Neuhold,
Y. M.; Hatwell, K. R.; Zuberbuhler, A. D.; Karlin, K. D. Inorg. Chem.
2001, 40, 5754-5767.
Inorganic Chemistry, Vol. 46, No. 16, 2007 6771

Pan and Newcomb
Scheme 2
plots of kobs solved for pseudo-first-order conditions against
concentrations of substrate would not be linear.
The observed reactivity order in regard to the porphyrin-
iron-oxo species is not consistent with predictions based
on the electron-withdrawing effects of the aryl groups of the
porphyrin macrocycles. The redox potentials for oxidations
of porphyrin-iron(III) complexes show that the electron
demand of the macrocycles is in the order 2a < 2b < 2c.9,10
Increasing electron demand from the macrocycle should
result in increasingly reactive metal-oxo complexes,8 and
that order of reactivity was found for the iron(IV)-oxo
porphyrin radical cations.18,30 With complexes 2, however,
the opposite kinetic trend is found.
Figure 4. Observed rate constants for the reaction of benzyl alcohol with
2a in the presence of added complex 1a. The slope of the line is -1.34 (
0.36.
MCPBA or PhIO ultimately lead to porphyrin-metal-oxo
products with the metals increased in oxidation state by only
+1.
One test of the disproportionation equilibrium in Scheme
2 is to attempt to suppress the oxidation reaction by adding
excess complex 1 to the reaction mixture. A series of
reactions of 2a with benzyl alcohol was performed with
varying amounts of iron(III) species 1a added and other
concentrations held constant. The reaction rate clearly
decreased as increasing amounts of 1a were added. For the
reaction sequence for Scheme 2 with a fast equilibrium
relative to the substrate oxidation, the rate law for oxidation
would be given by eqs 2 and 3, where k3 is the second-
order rate constant for oxidation by species 3 and Keq is the
equilibrium constant for the disproportionation reaction.
Under pseudo-first-order conditions, the observed rate con-
stant kobs is expected to be inversely proportional to the
concentration of species 1. Figure 4 shows the results of the
kinetic studies with added 1a in log-log format. As predicted
from Scheme 2 and eq 3, the kinetic order for 1a is
approximately -1.
One logical explanation for the observed relative reac-
tivities of complexes 2 is that species 2 are not the
predominant oxidants in the reactions. If the porphyrin-
iron(IV)-oxo intermediates rapidly establish a dispropor-
tionation equilibrium, then the major oxidant in the system
might be the high-valent iron-oxo species 3 with iron in
the formal oxidation state of iron(V), presumably an iron(IV)-
oxo porphyrin radical cation (Scheme 2). Such an equilibrium
with the reaction of a high-valent iron-oxo species is
consistent with the reactions of (TMP)FeIV(O) in polar
solvents.13 Similarly, porphyrin-manganese(IV)-oxo spe-
cies appear to react largely or entirely via porphyrin-
manganese(V)-oxo species produced in a disproportionation
equilibrium the same as that shown in Scheme 2.14
Oxidation reactions proceeding according to the mecha-
nism in Scheme 2 are consistent with the findings of apparent
inverted reactivity patterns. The disproportionation equilib-
rium will be increasingly less favorable as the electron
demand of the macrocycle increases. Thus, for example,
smaller concentrations of active oxidant 3c are expected for
the (TPFPP) system 2c than for the other iron(IV)-oxo
species, resulting in the slower consumption of species 2c.
That is, the changes in electron demand of the macrocycle
can have counteracting effects on the observed rates of
reactions; reactions of the true oxidants increase in rate with
increasing electron withdrawal by the macrocycle, but the
population of reactive species decreases with increasing
electron demand of the macrocycle. Furthermore, oxidation
by a species in a higher metal valence state than that of
species 2 also provides a convenient “two-electron” oxo-
transfer reagent that can react without the formation of
intermediate organic radical ions. The reaction presented in
Scheme 2 also presents a reasonable explanation for how
two-electron oxo-transfer oxidation reactions of porphyrin-
metal(III) complexes by sacrificial oxidations such as
d[Product]/ dt ) k3[Sub][3]
(2)
(3)
d[Product]/ dt ) k3Keq[Sub][H2O][2]2/[1]
Another test of the mechanism in Scheme 2 is possible in
principle but not in practice. The addition of water to the
reaction mixture might be expected to push the equilibrium
in Scheme 2 to the right and increase the overall rate of
reaction by increasing the concentration of active oxidant 3.
When transient 2a was produced in acetonitrile-water with
an excess of MCPBA, the formation of species 3a was
observed by UV-vis spectroscopy. In fact, it was possible
to convert 2a completely to the iron(IV)-oxo porphyrin
radical cation 3a with excess MCPBA. Unfortunately, water
is known to stabilize iron(IV)-oxo porphyrin radical cat-
ions,18,27 which explains why species 3a accumulated in the
acetonitrile-water mixture, and kinetic studies with water
present cannot be compared directly to those in the absence
of water. The stabilization of the compound I analogue 3a
by water is similar to the stabilization previously observed
with water-soluble porphyrin-iron-oxo27 and porphyrin-
manganese(V)-oxo species.14 The origin of the stabilizing
(30) Fujii, H. J. Am. Chem. Soc. 1993, 115, 4641-4648.
6772 Inorganic Chemistry, Vol. 46, No. 16, 2007

Porphyrin-Iron(IV)-Oxo Intermediates
effect is not obvious6 and deserves further study, but the point
for this work is that we could not use the results of reactions
in acetonitrile-water to understand the equilibrium in the
reaction shown in Scheme 2.
The important conclusion from the above studies is that
when reactions of iron(IV)-oxo species are studied, the
active oxidants apparently were iron-oxo derivatives in
higher oxidation states than the observable species 2. This
complicates an analysis of the kinetic data in regard to the
absolute values for the observed rate constants because the
experimental values are most likely the products of the
disproportionation equilibrium constants times the rate
constants for oxidations by the (undetectable) high oxidation
state metal-oxo species or also could be convolutions of
rate constants for these two processes if the equilibrations
are not fast relative to the oxidations. Nonetheless, relative
rate constants for reactions by a given species 2 can be
analyzed in a meaningful manner if the equilibria in Scheme
2 are rapidly established relative to the oxidation reactions
proper. In consideration of relative rate constants, the
concentration of the high valent iron-oxo species would
cancel in the relative rate expression, and the relative rate
constants for reactions of the high valent iron-oxo species
3 would be evaluated directly.
In the analysis that follows, we assume that the equilibria
in Scheme 2 are rapidly established for the three iron(IV)-
oxo species. Thus, the rate constants for disproportionation
and comproportionation are expected not to be convoluted
with the relative rate constants for oxidation reactions by
the high-valent iron-oxo species 3. This premise is supported
by the excellent free-energy correlations found for reactions
of the series of substituted benzyl alcohols, where the
velocities of the reactions varied by more than 2 orders of
magnitude for reactions of benzyl alcohol and 4-methoxy-
benzyl alcohol.
The most electron-deficient porphyrin we used was the
(TPFPP)-substituted system in 1c. Rate constants for reac-
tions of the compound I analogue (TPFPP)+•FeIV(O)(ClO4)
in CH2Cl2 with cis-cyclooctene, cyclohexene, and cis-stilbene
are 120, 220, and 190 M-1 s-1,18 or about 4 orders of
magnitude larger than the rate constants found here for the
reactions of 2c with the same substrates. These ratios provide
a crude approximation for the equilibrium constant in Scheme
2, although it is possible that the difference in solvents for
the two sets of studies might have a large effect on the
equilibria. The equilibrium constant deduced for the analo-
gous porphyrin-manganese(IV)-oxo species, (TPFPP)-
MnIV(O), disproportionating to the manganese(III) species
and manganese(V)-oxo species in CH3CN solvent, was of
the same order of magnitude.14
Figure 5. Linear free-energy relationships for rate constants for reactions
of 2b with benzyl alcohols, where the labels indicate the substituent on the
benzyl alcohol. (A) Hammett plots with σ values (open circles and dashed
lines) and σ+ values (squares and solid line). (B) Dual-parameter analysis
after Jiang;34 the calculated rate constants are from eq 4 in the text using
the F values from Table 3.
concludes that steric effects were important in this case, with
limited access of the bulky alcohol to the iron-oxo species.
The kinetic isotope effects in oxidations of benzyl alcohol
and its perdeuterated analogue were kH/kD ) 5.2, 4.5, and
5.7 for 3a, 3b, and 3c, respectively, indicating a large degree
of C-H bond breaking in the transition states for the
reactions. Similar kinetic isotope effects were observed in
hydroxylations of benzyl alcohol by other transition-metal-
oxo complexes.32,33
The oxidations of the para-substituted benzyl alcohols
provide insights into the electronic demands in the transition
states of the oxidation reactions. A conventional Hammett-
function analysis with the σ-substituent values gives poor
results, and an analysis with σ+-substituent values leads to
some improvement (Figure 5A). Analysis of the rate
constants with a dual-parameter function that separates polar
and spin-delocalization effects of the substituents gives
excellent fits, however, and appears to be most appropriate
for these reactions. We used the dual-parameter analysis
developed by Jiang.34 In this approach, para substituents have
a polar substituent value, σmb in eq 4, and a spin-delocal-
•
ization substituent value, σjj . The relative rate constants for
The rate constants for the alcohol oxidations demonstrate
both electronic and steric effects. Rate constants for the
reactions of 1-phenylethanol were larger than those for the
reactions of benzyl alcohol, apparently reflecting electronic
effects that result in a weaker benzylic C-H bond in the
former alcohol. Diphenylmethanol, which has a much
reduced C-H bond energy from that in benzyl alcohol,31
reacted less rapidly than 1-phenylethanol, however, and one
the reactions are analyzed by iteration of the F values to give
the best fit for the line.34 Figure 5B shows the dual-parameter
(31) McMillen, D. F.; Golden, D. M. Ann. ReV. Phys. Chem. 1982, 33,
493-532.
(32) Zhang, R.; Yu, W. Y.; Lai, T. S.; Che, C. M. Chem. Commun. 1999,
1791-1792.
(33) Oh, N. Y.; Suh, Y.; Park, M. J.; Seo, M. S.; Kim, J.; Nam, W. Angew.
Chem., Int. Ed. 2005, 44, 4235-4239.
(34) Jiang, X.-K. Acc. Chem. Res. 1997, 30, 283-289.
Inorganic Chemistry, Vol. 46, No. 16, 2007 6773

Pan and Newcomb
Table 3. Reaction Parameters for Oxidations of Benzyl Alcoholsa
spin-delocalization effects are important in the benzyl alcohol
oxidation reactions,34 and the values of the ratios obtained
here are similar to those found for some additions of
electrophilic radicals to substituted styrenes37,38 and for
benzylic H-atom abstractions from substituted toluenes by
the electrophilic bromine atom.39 Development of radical
character at the benzylic position in the transition states for
oxidations of the benzyl alcohols is likely the major reason
why the kinetic results did not correlate well with conven-
tional Hammett σ and σ+ values.
In summary, the studies reported in this work add kinetic
results for transition-metal-oxo reactions that can be com-
pared with other kinetic data to understand the mechanistic
details of oxidation reactions. Inverted reactivity patterns
were found, with the iron(IV)-oxo species containing the
most electron-withdrawing porphyrin reacting least rapidly,
similar to earlier findings with porphyrin-manganese(IV)-
oxo species,14 and the rate of the oxidation reaction was
shown to be inversely proportional to the concentration of
added porphyrin-iron(III) complex. These results indicate
that porphyrin-iron(IV)-oxo species disproportionate to
give iron(III) species and high-valent iron-oxo species,
presumed to be iron(IV)-oxo porphyrin radical cations, that
are the true oxidants in reactions with alkenes and alcohols.
Linear free-energy analyses of reactions of para-substituted
benzyl alcohols indicate that considerable amounts of positive
charge and spin character develop on the benzylic carbons
in the transition states for the oxidation reactions.
F+
Fmb
Fjj
•
porphyrin-iron-oxo
2a, (TDCPP)FeIV(O)
2b, (TDFPP)FeIV(O)
2c, (TPFPP)FeIV(O)
-1.8
-1.7
-1.7
-1.58
-1.51
-1.46
2.34
2.04
1.61
a F+ values are reaction parameters obtained by taking the least-squares
fit for data against the Hammett σ+-substituent values. Fmb and Fjj• are values
from the least-squares fits for the dual-parameter equation developed by
•
Jiang, with σmb and σjj values from ref 34.
fit for reactions of 2b, where the correlation coefficient is R
) 0.999. Good fits also were obtained for 2a (R ) 0.995)
and 2c (R ) 0.994) (Supporting Information). The results
for the dual-parameter analysis are listed in Table 3, which
also contains the F+ values that were found when the data
was analyzed in terms of the Hammett σ+-substituent values.
•
•
log(kY/kH) ) Fmbσmb + Fjj σjj + C
(4)
As expected for electrophilic oxidants, the F+ values are
negative, demonstrating positive charge development on the
substrate in the transition states for the oxidation reactions.
In the dual-parameter approach, Fmb also is negative for the
same reason. The Fmb values and F+ values are similar for
the three oxidants, which is the expected behavior, because
charge development in reactions of porphyrin-metal-oxo
species is sensitive to the axial ligand but relatively insensi-
tive to the aryl group substituents of the porphyrin. The
degree of charge development found here is similar to that
reported previously (F+ values in the range of -1.8 to -2.0)
for styrene epoxidation reactions effected by iron(IV)-oxo
porphyrin radical cations with the weak- and intermediate-
binding axial ligands hydroxide,35 triflate,36 and perchlorate.18
Acknowledgment. We thank the National Institutes of
Health and the National Science Foundation for financial
support and Prof. R. Zhang for helpful discussions.
•
The spin-delocalization reaction parameters Fjj obtained
Supporting Information Available: UV-vis spectra of 1b,
1c, 2b, and 2c, plots of rate constants for 1-phenylethanol
oxidations, and dual-parameter plots for oxidation reactions with
2a and 2c. This material is available free of charge via the Internet
at http://pubs.acs.org.
in the dual-parameter analyses are instructive. These values
decrease as the porphyrin radical stabilizing effects increase,
reflecting reduced radical character developing on the
substrate with a more stabilizing porphyrin. The absolute
•
values of the Fjj terms are larger than those of the polar
IC700395J
•
reaction parameters Fmb, with Fmb/Fjj values in the range of
(37) Guo, G. H. X.; Sun, S. S. X.; Ji, G. Z.; Jiang, X.-K. J. Chem. Res.,
Synop. 1993, 166-167.
(38) Jiang, X.-K.; Liu, W. W. Z.; Wu, S. H. J. Phys. Org. Chem. 1994, 7,
-0.7 to -0.9. Such ratios demonstrate that both polar and
(35) Groves, J. T.; Watanabe, Y. J. Am. Chem. Soc. 1986, 108, 507-508.
(36) Song, W. J.; Ryu, Y. O.; Song, R.; Nam, W. J. Biol. Inorg. Chem.
2005, 10, 294-304.
96-104.
(39) Jiang, X.-K.; Liu, W. W. Z.; Wu, S. H. Tetrahedron 1994, 50, 7503-
7512.
6774 Inorganic Chemistry, Vol. 46, No. 16, 2007