Targeted proton delivery in the catalyzed reduction of oxygen to water by bimetallic pacman porphyrins

Article abstract of DOI:10.1021/ja049115j

A combined experimental and theoretical investigation of the role of proton delivery in determining O₂ reduction pathways catalyzed by cofacial bisporphyrins is presented. A homologous family of dicobalt(II) Pacman porphyrins anchored by xanthene [CO₂(DPX) (1) and CO ₂(DPXM) (3)] and dibenzofuran [CO₂(DPD) (2) and CO ₂(DPDM) (4)] have been synthesized, characterized, and evaluated as catalysts for the direct four-proton, four-electron reduction of O₂ to H₂O. Structural analysis of the intramolecular diiron(III) μ-oxo complex Fe₂O(DPXM) (5) and electrochemical measurements of 1-4 establish that Pacman derivatives bearing an aryl group trans to the spacer possess structural flexibilities and redox properties similar to those of their parent counterparts; however, these trans-aryl catalysts exhibit markedly reduced selectivities for the direct reduction of O₂ to H ₂O over the two-proton, two-electron pathway to H₂O ₂. Density functional theory calculations reveal that trans-aryl substitution results in inefficient proton delivery to O₂-bound catalysts compared to unsubstituted congeners. In particular, the HOMO of [CO₂(DPXM)(O₂)]⁺ disfavors proton transfer to the bound oxygen species, funneling the O-O activation pathway to single-electron chemistry and the production of H₂O₂, whereas the HOMO of [CO₂(DPX)(O₂)]⁺ directs protonation to the [CO₂O₂] core to facilitate subsequent multielectron O-O bond activation to generate two molecules of H₂O. Our findings highlight the importance of controlling both proton and electron inventories for specific O-O bond activation and offer a unified model for O-O bond activation within the clefts of bimetallic porphyrins.

Full text of DOI:10.1021/ja049115j

Published on Web 07/14/2004
Targeted Proton Delivery in the Catalyzed Reduction of
Oxygen to Water by Bimetallic Pacman Porphyrins
†
†
‡
,‡
Christopher J. Chang, Zhi-Heng Loh, Chunnian Shi, Fred C. Anson,* and
,
†
Daniel G. Nocera*
Contribution from the Department of Chemistry, 6-335, Massachusetts Institute of Technology,
7
7 Massachusetts AVenue, Cambridge, Massachusetts 02139, and DiVision of Chemistry and
Chemical Engineering, Arthur Amos Noyes Laboratory, California Institute of Technology,
Pasadena, California 91125
Received February 17, 2004; E-mail: nocera@mit.edu
Abstract: A combined experimental and theoretical investigation of the role of proton delivery in determining
O
2
reduction pathways catalyzed by cofacial bisporphyrins is presented. A homologous family of dicobalt(II)
Pacman porphyrins anchored by xanthene [Co (DPX) (1) and Co (DPXM) (3)] and dibenzofuran [Co (DPD)
2) and Co (DPDM) (4)] have been synthesized, characterized, and evaluated as catalysts for the direct
four-proton, four-electron reduction of O to H O. Structural analysis of the intramolecular diiron(III) µ-oxo
complex Fe O(DPXM) (5) and electrochemical measurements of 1-4 establish that Pacman derivatives
2
2
2
(
2
2
2
2
bearing an aryl group trans to the spacer possess structural flexibilities and redox properties similar to
those of their parent counterparts; however, these trans-aryl catalysts exhibit markedly reduced selectivities
for the direct reduction of O
theory calculations reveal that trans-aryl substitution results in inefficient proton delivery to O
compared to unsubstituted congeners. In particular, the HOMO of [Co
2
to H
2
O over the two-proton, two-electron pathway to H
2
O
2
. Density functional
-bound catalysts
2
+
2
(DPXM)(O
2
)] disfavors proton transfer
to the bound oxygen species, funneling the O-O activation pathway to single-electron chemistry and the
+
production of H
2
O
2
, whereas the HOMO of [Co
2
(DPX)(O
2
)] directs protonation to the [Co
2 2
O ] core to facilitate
subsequent multielectron O-O bond activation to generate two molecules of H
2
O. Our findings highlight
the importance of controlling both proton and electron inventories for specific O-O bond activation and
offer a unified model for O-O bond activation within the clefts of bimetallic porphyrins.
Introduction
The role of a second proximate metal site for achieving
selective proton-coupled reduction of O2 to H2O in synthetic
Cytochrome c oxidase (COX) and related heme/copper
terminal oxidases are the fuel cells of aerobic organisms. These
enzymes catalyze the selective and complete four-proton, four-
electron conversion of oxygen to water without releasing
partially reduced peroxide (or superoxide) intermediates that
1
2-16
bimetallic catalysts is also yet to be determined.
Several
porphyrin templates bearing a distal metal-binding cap catalyze
the direct four-proton, four-electron reduction of O2 to H2O at
physiological pH with high selectivity over the more common
two-proton, two-electron pathway to afford H2O2.1
7-25
These
are toxic to cells.1-7 COX is distinguished structurally from other
heme-dependent proteins of O2 metabolism, owing to the
presence of an essential copper metal center proximate to the
heme cofactor. The catalytic reaction cycle of O2 reduction by
the bimetallic heme/CuB active site of COX appears, however,
to proceed through heme-oxygen intermediates that are similar
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Massachusetts Institute of Technology.
California Institute of Technology
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10.1021/ja049115j CCC: $27.50 © 2004 American Chemical Society
J. AM. CHEM. SOC. 2004, 126, 10013-10020
9
10013

A R T I C L E S
Chang et al.
Chart 1
catalysts exhibit comparable selectivities for the four-proton,
four-electron pathway with or without a second redox-active
dibenzofuran) are compared to those of analogues that bear an
aryl group trans to the spacer (DPXM ) diporphyrin xanthene
methoxyaryl, DPDM ) diporphyrin dibenzofuran methoxyaryl).
The results obtained from X-ray structural analysis, electro-
chemistry, and the electrocatalytic reduction of O2, together with
density functional theory calculations, identify critical structural
and electronic features that govern the selectivity for O2
reduction. We find that installation of a trans-aryl group into
the Pacman motif leads to an appreciably decreased selectivity
for the four-proton, four-electron pathway by diverting the
delivery of a proton to the [Co2O2] core. Our results show that
targeted proton delivery is required for the direct reduction of
O2 to H2O catalyzed by cofacial bisporphyrins and provide a
basis for designing systems for selective bond-making and bond-
breaking catalysis by proton-coupled electron transfer (PCET).
metal ion bound in the distal cap.2
0-23
In addition, cofacial
2
6,27
Pacman porphyrins containing two cobalt centers,
and one Lewis acidic metal, or one cobalt and one metal-free
one cobalt
28
2
9,30
subunit
are all effective catalysts for the direct production
of H2O from O2.
Taken together, the results from these biological and synthetic
catalysts imply that the selective reduction of O2 to H2O over
H2O2 steps beyond the idea of simple redox cooperativity
between proximate metal centers. Noting that O2 reduction
requires both proton and electron equivalents, we sought to
interrogate the role of proton delivery in determining O2
reduction pathways catalyzed by bimetallic systems. In this
report, we present experimental and theoretical studies of the
proton-coupled O2 reduction chemistry catalyzed by a family
of dicobalt(II) cofacial bisporphyrins. The structural and redox
properties, catalytic behavior, and electronic structures of
bimetallic Pacman porphyrins anchored by xanthene (DPX )
diporphyrin xanthene) and dibenzofuran (DPD ) diporphyrin
Results
Synthesis and Structural Chemistry. Dicobalt(II) complexes
3
1,32
33
32,34
of the four Pacman systems DPX,
DPXM, DPD,
and
(
(
(
(
(
(
(
22) Ricard, D.; Didier, A.; L’Her, M.; Boitrel, B. ChemBioChem 2001, 2, 144-
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077-4082.
26) Chang, C. K.; Liu, H. Y.; Abdalmuhdi, I. J. Am. Chem. Soc. 1984, 106,
33
DPDM (Chart 1) are obtained by reaction of the corresponding
free base bisporphyrins with CoCl2 in the presence of 2,6-
lutidine. Purification by column chromatography in an inert
atmosphere followed by recrystallization furnishes homobime-
tallic complexes Co2(DPX) (1), Co2(DPD) (2), Co2(DPXM) (3),
1
3
2
7
1
4
2
725-2726.
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E.; Carpenter, S. D.; Nocera, D. G. Inorg. Chem. 2002, 41, 3102-3109.
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1
1729.
(
29) Lui, H.-Y.; Abdalmuhdi, I.; Chang, C. K.; Anson, F. C. J. Phys. Chem.
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1, 1158-1166.
1
(
(34) Deng, Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2000, 122, 410-
411.
9
10014 J. AM. CHEM. SOC.
9
VOL. 126, NO. 32, 2004

Proton Delivery by Bimetallic Pacman Porphyrins
A R T I C L E S
Table 2. Selected Bond Lengths (Å) and Angles (deg) for
Table 1. Crystallographic Data for Fe2O(DPXM) (5)
Fe2O(DPXM) (5)
empirical formula
fw
C105H122Cl8Fe2N8O6
1987.41
Bond Lengths (Å)
2.081(5)
2.084(4)
2.085(5)
2.099(4)
1.786(3)
temp
wavelength
cryst syst
space group
unit cell dimensions
183(2) K
0.71073 Å
triclinic
P1h
a ) 15.1206(6) Å
b ) 16.0783(7) Å
c ) 24.5229(11) Å
R ) 72.500(1)°
â ) 79.253(1)°
γ ) 66.396(1)°
5195.3(4) Å
2
1.270 Mg/m
0.540 mm
2088
Fe(1)-N(1)
Fe(1)-N(2)
Fe(1)-N(3)
Fe(1)-N(4)
Fe(1)-O(1)
Fe(2)-N(5)
Fe(2)-N(6)
Fe(2)-N(7)
Fe(2)-N(8)
Fe(2)-O(1)
2.091(4)
2.082(4)
2.091(4)
2.085(4)
1.791(3)
Bond Angles (deg)
O(1)-Fe(1)-N(3) 104.77(17)
O(1)-Fe(2)-N(5) 103.88(16)
O(1)-Fe(2)-N(7) 108.29(17)
N(5)-Fe(2)-N(7) 147.80(17)
O(1)-Fe(2)-N(6) 106.56(17)
O(1)-Fe(1)-N(4) 107.40(17)
N(3)-Fe(1)-N(4)
83.92(19)
O(1)-Fe(1)-N(2) 105.79(16)
N(3)-Fe(1)-N(2) 87.52(17)
3
vol
Z
N(5)-Fe(2)-N(6)
N(7)-Fe(2)-N(6)
84.51(17)
87.67(17)
3
N(4)-Fe(1)-N(2) 146.82(17)
O(1)-Fe(1)-N(1) 105.12(17)
N(3)-Fe(1)-N(1) 150.11(17)
density (calculated)
abs coeff
F(000)
-
1
O(1)-Fe(2)-N(8) 103.86(16)
N(5)-Fe(2)-N(8)
N(7)-Fe(2)-N(8)
87.57(17)
83.54(17)
N(4)-Fe(1)-N(1)
N(2)-Fe(1)-N(1)
87.21(19)
84.46(17)
cryst size
0.36 mm × 0.11 mm × 0.10 mm
N(6)-Fe(2)-N(8) 149.56(17)
θ range for data collection
reflns collected
independent reflns
data/restraints/parameters
2.37-25.00°
23352
17671 [R(int) ) 0.0387]
17671/14/1144
1.051
2
GOF on F
final R indices [I > 2σ(I)]
R1 ) 0.0858
wR2 ) 0.2103
R1 ) 0.1311
R indices (all data)
wR2 ) 0.2496
-
3
largest diff peak
largest diff hole
1.554 e Å
-
3
-0.787 e Å
and Co2(DPDM) (4) in excellent yields (>90%). The steric
tuning provided by the choice of xanthene or dibenzofuran
spacer or introduction of an aryl group trans to the spacer
provides a homologous series of dicobalt(II) cofacial bispor-
phyrins spanning a wide range of vertical pocket sizes for further
study.
Installation of a single rigid pillar into the cofacial bispor-
phyrin motif yields face-to-face systems where the motion of
macrocyclic subunits with respect to each other is constrained
to the vertical dimension (e.g., the Pacman effect); this vertical
Pacman flexibility is critical for accommodating reaction
Figure 1. Crystal structure of 5. Thermal ellipsoids are drawn at the 25%
probability level. Hydrogen atoms have been omitted for clarity.
27,32,35-37
intermediates during catalysis.
Comparative structural
analysis of biszinc(II) and bisiron(III) µ-oxo complexes of DPD
demonstrates that this platform can open and close its binding
pocket by over 4 Å in metal-metal distances in the presence
of suitable ligands. An analogous intramolecular bisiron(III)
µ-oxo complex is also obtained for the DPX template under
similar conditions.32
To test whether the same type of Pacman effect would occur
for cofacial platforms that contain an aryl group trans to the
spacer, we prepared and crystallized the intramolecular bisiron-
as the torsion angle between the two meso-carbon-spacer
bonds) confirms that the Pacman flexibility of the DPXM system
is confined to the vertical direction. The compound exhibits a
bent Fe-O-Fe angle of 155.2°. The five-coordinate iron atoms
are raised 0.56 Å out of their respective 24-atom macrocyclic
planes, though typical Fe-N (davg ) 2.088 Å) and Fe-O (davg
) 1.788 Å) distances are observed.
Compound 5 completes the structurally homologous series
of open and closed forms of Pacman porphyrins shown in Figure
2. The structural comparison establishes that the introduction
of an aryl group trans to the spacer does not greatly hinder the
vertical Pacman flexibility of the cofacial platforms relative to
their unsubstituted counterparts. More generally, the results of
Figure 2 illustrate the ability of the cofacial porphyrins to clamp
their “jaws” down on exogenous substrates for DPX or DPD
bridges with or without trans-aryl substitution.
3
4
(III) µ-oxo complex Fe2O(DPXM) (5). Crystallographic data
and selected geometrical measurements for the compound are
provided in Tables 1 and 2, respectively. The structure of 5 is
depicted in Figure 1. The clamping action of the porphyrin
subunits in µ-oxo complex 5 is revealed by its reduced
interplanar angle (IPA) of 25.4° and shortened metal-metal
distance of 3.489 Å compared to the relaxed Zn2(DPXM)
compound (IPA ) 32.9°, Zn-Zn ) 5.913 Å).33 The small
torsional twist between porphyrin subunits in 5 (9.5°, defined
Electrochemistry. Electrochemical measurements of 1-4
verify that the redox properties of the parent DPX and DPD
systems are not appreciably perturbed by introduction of an aryl
group trans to the spacer. Table 3 lists the oxidative redox
potentials of the dicobalt(II) bisporphyrin systems. Cyclic
voltammograms of Co2(DPXM) (3) exhibit two reversible one-
(
(
(
35) Pistorio, B. J.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2002, 124,
884-7885.
36) Chang, C. J.; Loh, Z.-H.; Deng, Y.; Nocera, D. G. Inorg. Chem. 2003, 42,
262-8269.
37) Hodgkiss, J. M.; Chang, C. J.; Pistorio, B. J.; Nocera, D. G. Inorg. Chem.
003, 42, 8270-8277.
7
8
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J. AM. CHEM. SOC.
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VOL. 126, NO. 32, 2004 10015

A R T I C L E S
Chang et al.
Figure 2. Comparative views of the open and closed forms of the Pacman DPXM platform, (a) Zn2(DPXM) and (b) 5, respectively. Hydrogen atoms have
been omitted for clarity.
Table 3. Electrochemical and Electrocatalytic Data for Cofacial
Bisporphyrins 1-4
electrocatalytic O
2
reduction
% H O product
Eox/V vs Ag/AgCl
E
disk vs Ag/AgCl
2
1
2
3
4
+0.28, +0.17
+0.33
+0.31, +0.14
+0.33
+0.38
+0.37
+0.24
+0.25
72
80
52
46
Figure 3. Thin-layer cyclic voltammograms for (a) 3 in tolunitrile and (b)
in nitrobenzene, using 0.1 M n-tetrabutylammonium perchlorate (TBAP)
as a supporting electrolyte. Scan rate ) 10 mV/s, potentials reported vs
Ag/AgCl.
Figure 4. Rotating Pt ring-disk voltammograms for reduction of O2 at
pyrolytic graphite disks coated with (a) 1, (b) 2, (c) 3, and (d) 4. Rotation
rate, 100 rpm; disk current, S ) 10 µA; ring current, S ) 5 µA; supporting
electrolyte, 0.5 M HClO4/1.5 M TFA saturated with air for 1 and 2, 2 M
HClO4 saturated with air for 3 and 4; ring held at +1.0 V vs Ag/AgCl.
4
electron oxidation waves at +0.31 and +0.14 V vs Ag/AgCl
(Figure 3a). The splitting of the oxidation processes arises from
strong interactions between two proximate porphyrin π
Catalytic Reduction of O2. We next sought to examine the
effect of trans-aryl substitution on the selectivity for four-proton,
four-electron versus two-proton, two-electron reduction of O2
catalyzed by these Pacman motifs. To this end, complexes 1-4
were screened for their electrocatalytic activity for O2 reduction
in acidic media. Figure 4 displays current-potential responses
for catalytic O2 reduction at a rotating graphite disk/platinum
ring electrode coated with 1-4, and the results are collected in
Table 3.
2
7,38-41
systems.
The mixed-valence behavior displayed by 3 is
similar to what is observed for the parent complex, Co2(DPX)
2
7
(1), at comparable potentials (E° ) +0.28 and +0.17 V).
Conversely, cyclic voltammograms of Co2(DPDM) (4) give a
single, reversible two-electron oxidative wave at a potential
2
7
identical to that of Co2(DPD) (2) (E° ) +0.33 V, Figure 3b),
establishing that the porphyrinic subunits in the dibenzofuran-
bridged platforms are too far apart to perturb each other
electronically. These electrochemical data show that the redox
behaviors of the DPXM and DPDM platforms mirror their
corresponding DPX and DPD counterparts.
The parent DPX and DPD complexes are selective catalysts
for the direct reduction of O2 to H2O over the more commonly
observed pathway to produce H2O2. Co2(DPX) (1) reduces O2
at a potential of +0.38 V vs Ag/AgCl, with 72% selectivity for
the four-proton, four-electron pathway to H2O (Figure 4a), and
Co2(DPD) (2) catalyzes O2 reduction at +0.37 V, with direct
(
38) Collman, J. P.; Hutchison, J. E.; Lopez, M. A.; Tabard, A.; Guilard, R.;
Seok, W. K.; Ibers, J. A.; L’Her, M. J. Am. Chem. Soc. 1992, 114, 9869-
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877.
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S.; Hutchison, J. E.; Collman, J. P. J. Am. Chem. Soc. 1992, 114, 9877-
27
production of H2O at 80% selectivity (Figure 4b). In contrast,
9
889.
(40) Le Mest, Y.; L’Her, M.; Saillard, J. Y. Inorg. Chim. Acta 1996, 248, 181-
DPXM and DPDM complexes bearing a trans-aryl group display
markedly lower H2O/H2O2 product ratios than their parent DPX
and DPD counterparts while exhibiting similar selectivities
1
91.
(41) Le Mest, Y.; Inisan, C.; Laouenan, A.; L’Her, M.; Talarmain, J.; El Khalifa,
M.; Saillard, J. Y. J. Am. Chem. Soc. 1997, 119, 6095-6106.
10016 J. AM. CHEM. SOC.
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Proton Delivery by Bimetallic Pacman Porphyrins
A R T I C L E S
compared to each other. Co2(DPXM) (3) catalyzes O2 reduction
at +0.24 V, with 52% proceeding along the four-proton, four-
electron pathway to produce H2O (Figure 4c); Co2(DPDM) (4)
catalyzes O2 reduction at +0.25 V, with 46% going directly to
H2O (Figure 4d). The catalytic studies clearly show that
installation of a trans-aryl group into the Pacman motif results
in decreased selectivity for the direct reduction of O2 to H2O,
with a comparable effect for both xanthene- and dibenzofuran-
bridged scaffolds. Because the structural flexibility and redox
behavior of the cofacial bisporphyrin systems are largely
unperturbed by trans-aryl substitution, more subtle electronic
and proton-coupled effects are inferred for this change in
catalytic selectivity.
cycles are 0.31 and 0.20 Å, respectively. The nonplanar
distortions result in appreciably less effective charge transfer
from the cobalt bisporphyrin fragment to the reduced O2
+
substrate for [Co2(DPXM)(O2)] (-0.237 e) compared to the
parent DPX counterpart (-0.284 e) and also lead to stronger
O-O bonding in the former. The Mulliken overlap populations
+
+
for the O-O units in [Co2(DPXM)(O2)] and [Co2(DPX)(O2)]
are +0.175 and +0.159 e, respectively.
The electronic and structural character of the highest occupied
molecular orbital (HOMO), which is the site of proton transfer
in acid-base reactions, is of greatest pertinence to O reduction.
2
Figure 5 illustrates significant differences between the HOMOs
+
+
of the [Co (DPX)(O )] and [Co (DPXM)(O )] species. The
2
2
2
2
Electronic Structure Calculations. Density functional theory
DFT) was applied to the parent (DPX) and trans-aryl-substituted
DPXM) derivatives of the [Co2(bisporphyrin)(O2)]+ in order
singly occupied HOMO of the DPX superoxo species consists
of localized molecular orbitals with significant π*(Co-O) and
π*(O-O) character on the [Co2O2] core, as well as a π-delo-
calized system of a1u symmetry on one of the porphyrin
macrocycles. The pronounced electron density on the superoxo
indicates it to be basic and to be the target of proton transfer.
(
(
to probe the origin of the diminished catalytic selectivity for
O2 to H2O reduction by trans-aryl-substituted Pacman porphy-
rins. The object of these calculations was a Co(III)/Co(III)
superoxo intermediate because experimental studies implicate
this O2-carrying species as the critical entry point into the
+
Conversely, the singly occupied HOMO of [Co2(DPXM)(O2)]
consists solely of a porphyrin π system of a1u symmetry, with
no electron density observed on the superoxo. This electronic
structure disfavors the targeted delivery of proton equivalents
to the [Co2O2] core.
38,41-43
catalytic O2 reduction cycle.
+
Geometry optimization of [Co2(DPX)(O2)] with a doublet
spin state affords a structure with the bridging O2 adduct
adopting an end-on geometry. To avoid complications arising
from predisposed structural models,41 no constraints were placed
on O2 binding in an end-on or side-on arrangement; in fact, the
end-on structure is also obtained from an initial input geometry,
using an idealized side-on [Co2O2] core. The Co centers are
displaced slightly out of the N4 porphyrin mean plane (davg )
Discussion
The selective conversion of O2 to H2O by heme/copper
terminal oxidases is made possible by their ability to effectively
balance proton and electron inventories. In particular, the
bimetallic heme/CuB active site of COX mediates these PCET
events through heme-oxygen intermediates that are analogous
0
.07 Å), giving a Co-Co distance of 4.35 Å, with Co-O bond
lengths averaging 1.83 Å. The calculated O-O bond length of
4
4
to those observed in monometallic heme proteins. Viewed
4
5
1
(
.35 Å is characteristic for a superoxo-bridged bimetallic unit
within a PCET framework, the complete reduction of O2 to
H2O requires four protons and four electrons for the cleavage
of two formal O-O bonds, whereas the partial reduction of O2
to H2O2 requires two protons and two electrons for the cleavage
of a single formal O-O bond. Specific activation of the second
O-O bond, which is the key determinant in producing H2O
instead of H2O2, is thus predicated on the proper delivery of
additional proton equivalents to substrate bound within the
reducing active site. In COX, spectroscopic and kinetics studies
of partially and fully reduced enzymes establish that the O-O
bond is broken upon the addition of three electrons and one
1.26-1.36 Å), resulting in a [CoIII2-(O2 )] configuration for
-
the Pacman [Co2O2] core. Mulliken population analysis reveals
that the total spin density on the [Co2O2] core is 1.068 e,
suggesting that the majority of the unpaired spin density is
localized on the [Co2O2] unit. The results are in good agreement
with the experimental observation of a 15-line EPR spectrum
+
27
for [Co2(DPX)(O2)(1,5-dicyclohexylimidazole)2]
and related
µ-superoxodicobalt(III) complexes of cofacially strapped FTF4
and pillared DPB bisporphyrins.3
8,41
+
The optimized geometry of [Co2(DPXM)(O2)] is similar to
4
6-49
proton.
We propose that this crucial proton and electron
that of its DPX analogue. A doublet spin state produces a
complex with an end-on O2 adduct bridging the two Co centers.
The Co-Co distance (4.50 Å) and average Co-O (1.88 Å) bond
length for the DPXM monocation species compare favorably
to values observed for the DPX analogue. The O-O bond length
stoichiometry for O-O bond cleavage is preserved in the O2
reduction reactivity displayed by cofacial bisporphyrins.
Scheme 1 presents a mechanistic model for the PCET
activation of the O-O bond by Pacman porphyrins. Previous
experimental studies have shown that the one- and two-electron
oxidized cofacial platforms are capable of binding O2, whereas
the fully reduced [Co2(bisporphyrin)] complex is unreactive to
(
1.32 Å) and unpaired spin density localized on the [Co2O2]
+
fragment (1.082 e total) for [Co2(DPXM)(O2)] also support
its assignment as a µ-superoxodicobalt(III) complex. In contrast
to the DPX superoxo species, however, trans-aryl substitution
results in significant nonplanar distortions of the porphyrin
38,41,42
the O2 substrate.
For the Pacman porphyrins reported here,
(
44) Babcock, G. T. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 12971-12973.
45) Chang, C. J.; Chang, M. C. Y.; Damrauer, N. H.; Nocera, D. G. Biochim.
Biophys. Acta 2004, 1665, 13-28.
subunits within the DPXM superoxo cleft. For [Co2(DPXM)-
(
+
(
O2)] , one porphyrin exhibits a ruffled-type conformation,
(
46) Hansson, O¨ .; Karlsson, B.; Aasa, R.; V a¨ nngård, T.; Malmstr o¨ m, B. G.
EMBO J. 1982, 1, 1295-1297.
whereas distortion of the other macrocycle is dominated by
saddling. The average mean plane deviations for these macro-
(47) Blair, D. F.; Witt, S. N.; Chan, S. I. J. Am. Chem. Soc. 1985, 107, 7389-
7399.
(
48) Morgan, J. E.; Verkhovsky, M. I.; Palmer, G.; Wikstr o¨ m, M. Biochemistry
(
(
42) Chang, C. K. J. Chem. Soc., Chem. Commun. 1977, 800-801.
43) Proniewicz, L. M.; Odo, J.; Goral, J.; Chang, C. K.; Nakamoto, K. J. Am.
Chem. Soc. 1989, 111, 2105-2110.
2001, 40, 6882-6892.
(49) Blomberg, M. R. A.; Siegbahn, P. E. M.; Babcock, G. T.; Wikstr o¨ m, M.
J. Am. Chem. Soc. 2000, 122, 12848-12858.
J. AM. CHEM. SOC.
9
VOL. 126, NO. 32, 2004 10017

A R T I C L E S
Chang et al.
Figure 5. Singly occupied HOMOs of (a) [Co2(DPX)(O2)]+ and (b) [Co2(DPXM)(O2)] . The structures on the left depict a side view, perpendicular to the
+
bridge plane, whereas the structures on the right display a top view, perpendicular to the porphyrin planes.
EPR studies establish that the one-electron oxidized CoII,III
cofacial porphyrin provides entry into the catalytic cycle. The
regulatory function for oxygen activation by using a proton to
mediate the transfer of the additional two electrons needed for
O-O bond cleavage. In the absence of a proton, a single electron
transfer yields the peroxide (a net two-electron transfer). In
addition, the proton has the dual function of weakening the O-O
bond upon protonation. The general model proposed in Scheme
1 also clarifies the perplexing observations of synthetic con-
structs that show similar or enhanced reactivity when the second
2
+
II,III
[Co2(bisporphyrin)(O2)] adduct formed from Co 2 and O2
is stable to superoxide release and is poised for further reaction.
Our results show that it is the basicity of the superoxo complex
that is the key determinant of the selectivity for O2 reduction.
We propose that targeted proton transfer to the [Co2O2] core of
[
Co2(bisporphyrin)(O2)]+ triggers a multielectron transport
process, bypassing one-electron processes to formal [Co2-
bisporphyrin)(O2)] peroxo-type intermediates that would favor
2
9,30
coordination site is empty
or replaced by an appropriate
28
(
Lewis acidic metal ion. The role of the second functional site,
whether that be another porphyrin, metal complex, or metal-
free coordination sphere, is to adjust the pKa of the oxygen
adduct. Because a cooperative redox activity is not required,
the site may be redox inactive or completely absent.
H2O2 production. Protonation followed by a two-electron
transfer provides the necessary equivalents to result in O-O
bond cleavage. In this case, an oxo-hydroxy species, similar to
the O-O bond cleavage product of COX,9
,46-48
would result;
subsequent reduction by an additional electron produces the fully
reduced product. We note however that a Co oxo species may
Concluding Remarks
IV
not be stable, and the system may drive through to the fully
reduced product. If the superoxo is not sufficiently basic,
inefficient proton transfer to [Co2(bisporphyrin)(O2)] would
We have investigated the effect of proton delivery on the
catalytic selectivity of a homologous set of cofacial Pacman
porphyrins. Our findings indicate that targeted proton transfer
is critical for selecting the four-proton, four-electron pathway
2
+
result in either reversible loss of O2 substrate or one-electron
reduction to the peroxide level, with subsequent generation of
H2O2. Thus, the key to the selective reduction of oxygen to
to H O over the more common two-proton, two-electron
+
pathway to H O . The O -carrying [Co (bisporphyrin)(O )]
2
2
2
2
2
+
water is the protonation state of the [Co2(bisporphyrin)(O2)]
species of Pacman systems DPX and DPD targets proton transfer
monocation species; targeted proton delivery to the superoxo
is essential for favoring multielectron over single-electron
chemistry for specific O-O activation and cleavage.
to the reducing [Co O ] core, favoring complete O-O cleavage
2
2
to produce two H O molecules. In contrast, the superoxo adduct
2
of trans-aryl DPXM and DPDM analogues disfavors protonation
The proposed scheme displayed in Figure 1 is appealing from
several perspectives. As mentioned above, the proper stoichi-
ometry of one proton and three electrons needed for O-O bond
cleavage is satisfied. The superoxo provides an important
of the [Co2O2] unit, resulting in a stronger O-O bond and
increased production of H2O2.
The combined experimental and theoretical findings have
important implications for the design of catalysts for specific
10018 J. AM. CHEM. SOC.
9
VOL. 126, NO. 32, 2004

Proton Delivery by Bimetallic Pacman Porphyrins
A R T I C L E S
Scheme 1
cleavage of O-O bonds. As discussed by Taube,50 cofacial
bisporphyrins fulfill the two general requirements for an
effective four-electron, four-proton O2 reduction catalyst: (i)
the bypass of kinetically available one-electron routes through
cooperative reactivity and (ii) the protection of peroxo-type
intermediates against protonation and release. The substantial
body of work on cofacial bisporphyrins as O2 reduction catalysts
has clarified the structural attributes of an effective architecture,
including the restriction of macrocyclic subunits to a face-to-
face arrangement with minimal lateral displacements, while
allowing sufficient vertical flexibility to bind and activate the
Solvents for synthesis were of reagent grade or better and were dried
3
1
according to standard methods. The Pacman porphyrins H
4
(DPX),
(DPDM) were synthesized as
described previously. All other reagents were used as received.
Co (DPX) (1). In a drybox, H (DPX) (120 mg, 0.10 mmol),
anhydrous cobalt(II) chloride (200 mg), 2,6-lutidine (0.2 mL), and THF
120 mL) were loaded in a 250-mL round-bottom flask. The mixture
4 4 4
H H (DPXM), and H
(DPD),34
33
33
2
4
(
was refluxed under nitrogen for 12 h. The solvent was removed in
vacuo, and the residue was purified by flash column chromatography
under an inert atmosphere (alumina, THF). Recrystallation from
dichloromethane/methanol gave 1 as an analytically pure purple
crystalline powder (121 mg, 95% yield). Anal. Calcd for C79
82
H -
2
6,27,51
O2 substrate.
Against this backdrop of expertise, we have
Co N O: C, 74.24; H, 6.47; N, 8.77. Found: C, 73.86; H, 6.42; N,
2
8
+
now established the importance of a proper electronic environ-
ment for the bound O2 substrate by directing proton transport.
In particular, we find that targeted proton transfer is required
for selective O-O reactivity and suggest that specific proto-
nation of the O2-carrying superoxo adduct bypasses the forma-
tion of peroxo-type adducts by facilitating multielectron pro-
cesses. In closing, our results highlight the importance of proton
transport and electronic structure in guiding catalytic O2
reduction pathways. Along these lines, we are now testing the
ability of monometallic Hangman constructs that control both
proton and electron inventories45,52-55 to catalyze selective O2
activation chemistry.
8.71. HRFABMS (M ) calcd for C79
2 8
H82Co N O m/z, 1276.528; found,
1276.526.
Co
condenser was charged with H
0.1 mL), CoCl (100 mg), THF (12 mL), and benzene (12 mL). The
2
(DPD) (2). In a drybox, a 100-mL flask equipped with a
4
(DPD) (50 mg, 0.045 mmol), 2,6-lutidine
(
2
mixture was refluxed under nitrogen for 12 h. The solvent was removed
in vacuo, and the residue was purified by flash column chromatography
under an inert atmosphere (alumina, THF). Recrystallation from
dichloromethane/methanol gave 2 as an analytically pure maroon
crystalline powder (50 mg, 91% yield). Anal. Calcd for C76
76
H -
Co O: C, 73.89; H, 6.20; N, 9.54. Found: C, 73.82; H, 6.26; N,
2
N
8
+
8
.94. HRFABMS (M ) calcd for C76
2 8
H76Co N O m/z, 1234.481; found,
1
234.480.
Co
in THF (15 mL) and benzene (10 mL) containing 2,6-lutidine (0.2 mL)
was added CoCl (200 mg). The resulting mixture was refluxed for 10
h under nitrogen and taken to dryness. The solvent was removed in
vacuo, and the residue was purified by flash column chromatography
under an inert atmosphere (neutral alumina, THF). Recrystallation from
dichloromethane/methanol gave 3 as an analytically pure brick-red
2 4
(DPXM) (3). To a solution of H (DPXM) (105 mg, 0.073 mmol)
Experimental Section
Materials. Aluminum oxide 60 (EM Science) was used for column
chromatography. Analytical thin-layer chromatography was performed
using JT Baker IB-F aluminum oxide (precoated sheets, 0.2 mm thick).
2
(
50) Taube, H. Prog. Inorg. Chem. 1986, 34, 607-625.
51) Collman, J. P.; Wagenknecht, P. S.; Hutchison, J. E. Angew. Chem., Int.
Ed. Engl. 1994, 33, 1537-1554.
(
powder (110 mg, 97% yield). Anal. Calcd for C95
102 8 5 2
H N O Co : C,
J. AM. CHEM. SOC. VOL. 126, NO. 32, 2004 10019
9

A R T I C L E S
Chang et al.
7
3.63; H, 6.37; N, 7.23. Found: C, 73.77; H, 6.53; N, 6.84. HRFABMS
were polished with 600 grit SiC paper (3M), sonicated in purified water
(MilliQ Plus), washed with acetone, and dried. Porphyrins were
adsorbed on the electrode surface by means of a dip-coating proce-
dure: the freshly polished electrode was dipped for 1 min in a 0.1
mM solution of the porphyrin in chloroform, removed, washed
immediately with pure chloroform, and dried in air. The dry, coated
electrodes were transferred to the aqueous supporting electrolytes and
utilized immediately.
+
(
M ) calcd for C95
H N
102 8
O
5
Co
(DPDM) (4). To a solution of H
in THF (8 mL) and benzene (8 mL) containing 2,6-lutidine (0.1 mL)
was added CoCl (120 mg). The resulting mixture was refluxed for 15
2
m/z, 1548.632; found, 1548.633.
Co
2
4
(DPDM) (52 mg, 0.037 mmol)
2
h under nitrogen and taken to dryness. The solvent was removed in
vacuo, and the residue was purified by flash column chromatography
under an inert atmosphere (neutral alumina, THF). Recrystallation from
dichloromethane/methanol gave 4 as an analytically pure blood-red
powder (51 mg, 91% yield). Anal. Calcd for C92
H, 6.15; N, 7.43. Found: C, 73.60; H, 6.49; N, 6.90. HRFABMS (M )
The commercial rotating graphite disk-platinum ring electrode (Pine
Instruments) was polished with 0.3 µm alumina on microcloth. The
H
92
N
8
O
5
Co
2
: C, 73.29;
+
collection efficiency of the rotating ring-disk electrode (RRDE)
calcd for C92
Fe O(DPXM) (5). A mixture of H
and FeBr (100 mg) in THF (7 mL) and benzene (5 mL) containing
,6-lutidine (0.1 mL) was refluxed under nitrogen for 5 h. The reaction
92 8 5
H N O Co
2
m/z, 1506.586; found, 1506.590.
3-/4-
6
employed was 0.39, as established by measurements with the Fe(CN)
2
4
(DPXM) (45 mg, 0.031 mmol)
couple. The percentage of oxygen reduction proceeding along the four-
electron pathway to produce water was calculated using the formula
2
2
fwater ) [N - (i /i )]/[N + (i /i )] where f
water
is the fraction of oxygen
R
D
R
D
was opened to air, and the solvent was removed by rotary evaporation.
The remaining residue was taken up in dichloromethane and vigorously
stirred with a 0.5 N NaOH solution (20 mL) for 30 min. The organic
phase was separated, washed with water (3 × 25 mL), dried over
reduced to water, N is the collection efficiency of the RRDE, and iR
and iD are the ring and disk currents, respectively.
Computational Methods. Density functional theory (DFT) calcula-
tions were carried out at the local density approximation (LDA) level
2 4
Na SO , and taken to dryness. Purification by column chromatography
57-60
of theory using the Amsterdam Density Functional program.
Part
(basic alumina, 85:15 chloroform/ethyl acetate) followed by recrystal-
of the calculations were performed on a home-built Linux cluster
consisting of 12 processors running in parallel. Gradient corrections
lization from dichloromethane/hexanes afforded analytically pure 5 (45
mg, 92% yield) as a brown crystalline solid. Anal. Calcd for
61
were introduced by using the Becke exchange functional (B) and the
C
95
H
102
N
8
O
6
Fe
2
: C, 73.16; H, 6.33; N, 7.19. Found: C, 73.01; H, 6.20;
62
Perdew-Wang (PW91) correlation functional. C and H were de-
+
N, 7.06. HRFABMS ([M - O] ) calcd for C95
102 8 5 2
H N O Fe m/z,
scribed by a Slater-type orbital double-ê basis set augmented by one
set of polarization functions. Co, N, and O atoms were described by a
Slater-type orbital triple-ê basis set augmented by one set of polarization
functions. Non-hydrogen atoms were assigned a frozen core potential,
treating as core the shells up to and including 2p for Co and 1s for C,
N, and O. Calculations on the doublet spin state were performed within
the unrestricted formalism. Population analyses were carried out using
the Mulliken method. Two minor structural simplifications were made
to the cobalt bisporphyrin models employed in the calculations: (i)
ethyl groups on the porphyrin macrocycles were replaced with methyl
groups and (ii) methyl groups on the xanthene pillar were replaced
with hydrogens.
1
542.636; found, 1542.633.
General Details of X-ray Data Collection and Reduction. X-ray
diffraction data were collected using a Siemens 3 circle diffractometer
equipped with a CCD detector. Measurements were carried out at -90
°
C using Mo KR (λ ) 0.71073 Å) radiation, which was wavelength
selected with a single-crystal graphite monochromator. Four sets of
data were collected, using ω scans and a -0.3° scan width. All
calculations were performed using a PC workstation. The data frames
were integrated to hkl/intensity, and final unit cells were calculated by
using the SAINT v.4.050 program from Siemens. The structures were
solved and refined with the SHELXTL v.5.03 suite of programs
developed by G. M. Sheldrick and Siemens Industrial Automation, Inc.,
1
995.
Acknowledgment. C.J.C. thanks the National Science Foun-
dation and the MIT/Merck Foundation for predoctoral fellow-
ships. Z.-H.L. gratefully acknowledges the benefits of the M.I.T.
Undergraduate Research Opportunities Program (UROP) and
the National Science and Technology Board (Singapore) for an
undergraduate scholarship. The National Institutes of Health
X-ray Structure of Fe
0.11 mm × 0.10 mm chocolate-colored crystal of plate morphology
2
O(DPXM)‚4CH
2
Cl
2
6
‚C H14 (5). A 0.36 mm
×
was obtained from slow diffusion of hexane into a dichloromethane
solution of the compound. The crystal was coated in STP oil treatment
and mounted onto a glass fiber. A total of 23 352 reflections were
collected in the θ range 2.37-25.00°, of which 17 671 were unique
(GM 47274) and the National Computational Science Alliance
(Rint ) 0.0387). The Patterson method was used to locate the iron atoms;
all remaining atoms were placed using the difference Fourier map.
Hydrogen atoms were placed in calculated positions using a standard
riding model and were refined isotropically. The largest peak and hole
in the difference map were 1.554 and -0.787 e Å , respectively. The
least-squares refinement converged normally, giving residuals of R1
(CHE020041N) provided funding for this work.
Supporting Information Available: X-ray crystallographic
file (CIF format) for 5. This material is available free of charge
via the Internet at http://pubs.acs.org.
-
3
)
0.0858 and wR2 ) 0.2103, with GOF ) 1.051.
Physical Measurements. Staff at the University of Illinois Mass
JA049115J
Spectrometry Laboratory carried out mass spectral analyses. Elemental
analyses were performed at Michigan State University. Absorption
spectra were obtained using a Cary-17 spectrophotometer, modified
by On-Line Instrument Systems (OLIS) to include computer control,
or a Spectral Instruments 440 Model spectrophotometer.
(
53) Chang, C. J.; Yeh, C.-Y.; Nocera, D. G. J. Org. Chem. 2002, 67, 1403-
406.
1
(
54) Chang, C. J.; Chng, L. L.; Nocera, D. G. J. Am. Chem. Soc. 2003, 125,
1866-1876.
(
55) Chng, L. L.; Chang, C. J.; Nocera, D. G. Org. Lett. 2003, 5, 2421-2424.
56) Yuasa, M.; Steiger, B.; Anson, F. C. J. Porphyrins Phthalocyanines 1997,
1, 181-187.
(
Electrochemical Apparatus and Procedures. Cylindrical pyrolytic
graphite rods with the edges of the graphitic planes explosed (Union
Carbide) were mounted to stainless steel shafts with heat-shrinkable
polyolefin tubing (Alpha Wire). The exposed graphite disk had an area
(57) ADF2000.02; Vrije Universiteit Amsterdam: Amsterdam, The Netherlands,
1999.
(58) Baerends, E. J.; Ellis, D. E.; Ros, P. Chem. Phys. 1973, 2, 41-51.
(59) Te Velde, G.; Bickelhaupt, F. M.; Baerends, E. J.; Fonseca Guerra, C.;
Van Gisbergen, S. J. A.; Snijders, J. G.; Ziegler, T. J. Comput. Chem. 2001,
2
of 0.32 cm . Electrode pretreatment and catalyst loading were carried
22, 931-967.
5
6
out using standard procedures. Briefly, the pyrolytic graphite rods
(60) van Gisbergen, S. J. A.; Snijders, J. G.; Baerends, E. J. Comput. Phys.
Commun. 1999, 118, 119-138.
(
61) Becke, A. D. Phys. ReV. A: At., Mol., Opt. Phys. 1988, 38, 3098-3100.
(
52) Yeh, C.-Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2001, 123,
(62) Perdew, J. P.; Wang, Y. Phys. ReV. B: Condens. Matter Mater. Phys. 1992,
1
513-1514.
46, 12947-12954.
10020 J. AM. CHEM. SOC.
9
VOL. 126, NO. 32, 2004