Substituted tren-capped porphyrins: Probing the influence of copper in synthetic models of cytochrome c oxidase

Article abstract of DOI:10.1039/b300604b

Tris(2-aminoethylamine) (tren)-capped porphyrins bearing electron donating or withdrawing groups on the amino functions of their tripod have been synthesised and the catalytic activity of each complex was carefully studied both as the iron and the iron-co

Full text of DOI:10.1039/b300604b

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Substituted tren-capped porphyrins: probing the influence of copper
in synthetic models of cytochrome c oxidase
Amandine Didier,a Maurice L’Herb and Bernard Boitrel*a
a Université de Rennes 1, UMR CNRS 6509, Institut de Chimie, 35042 Rennes Cedex, France.
E-mail: Bernard.Boitrel@univ-rennes1.fr; Fax: 02 2323 5637; Tel: 02 2323 6372
b Université de Bretagne Occidentale, Faculté des Sciences, UMR CNRS 6521, B.P. 809, 29285
Brest Cedex, France. E-mail: maurice.lher@univ.brest.fr; Fax: 02 9801 6594; Tel: 02 9801 6145
Received 20th January 2003, Accepted 7th March 2003
First published as an Advance Article on the web 19th March 2003
Tris(2-aminoethylamine) (tren)-capped porphyrins bearing
electron donating or withdrawing groups on the amino
functions of their tripod have been synthesised and the
catalytic activity of each complex was carefully studied
both as the iron and the iron–copper complexes: only one
of our iron–copper complexes was shown to be active and
selective towards the reduction of dioxygen to water.
tren, imidazole and quinoline pickets, benzyl-tren) differing
simultaneously by several structural parameters such as the
geometry, the flexibility, or the nature of the nitrogen atoms
have already been tested. So far, with our first generation com-
plexes,7 we have only probed the effect of the relative position
of the two metal centres, but the environment of copper has
never been investigated. The aim of the present work is to
examine the influence of substituents on the para position of
benzyl-tren. It is reasonable to expect these to modify the
electron density on the Cu site and thus its ability to interact
with the oxygen molecule bound to the iron porphyrin.
Introduction
Intensive studies have been devoted to the understanding of the
catalytic cycle by which cytochrome c oxidase (CcO) reduces
oxygen to water in the inner membrane of mitochondria. The
major effect of this final step in the respiratory chain is the
formation of the highly energetic molecule ATP, without any
leakage of the deleterious partially reduced intermediates.1
The nature of O2 interaction with the iron and copper metal
centers in CcO is of paramount importance. Indeed, many
issues remain unsolved, such as the role of copper during the
catalytic cycle in O2-bridging, and the type of O2-bound inter-
mediates, even if some of them were characterized by time-
resolved resonance Raman spectroscopy.2 Most researchers are
convinced that the catalytic cycle passes through the formation
of a heterobimetallic µ-peroxo intermediate.3–6 Nevertheless,
this very plausible hypothesis did not receive confirmation as
the numerous studies with synthetic model molecules did not
really clarify the matter. However, in former reports about the
activity of tren-capped porphyrins, we have shown that “iron-
only” porphyrins are efficient catalysts for the reduction of
dioxygen, when the complexes are adsorbed on graphite
electrodes in contact with aqueous media at pH close to 7.7 This
crucial observation demonstrates that the postulated µ-peroxo
complex is not an essential intermediate for the four-electron
reduction of oxygen, as long as electrons and protons can be
rapidly delivered to the catalytic site of a synthetic model.8 Our
conclusion, in agreement with recent spectroscopic results,9 is
supported by Yoshikawa et al. who suggested that the peroxo
derivative could be protonated by Tyr244, located in a closed
environment of the coordination sphere of copper, forming
a hydroperoxo adduct.10 In 1997, Collman et al. reported the
electrocatalytic reduction of dioxygen, using heterobimetallic
Fe–Cu or Co–Cu compounds, tethered with TACN (triaza-
cyclononane) or tren, in order to investigate the influence of the
presence of the two metals on the ratio of 2eϪ/4eϪ processes.11
Their conclusion was that the iron-only catalysts studied were
not active and that Cu was essential to the 4eϪ process. How-
ever, in a recent study, with different molecules, these authors
came to the conclusion that the presence of Cu is not needed for
the reduction of O2 to water.12
Results and discussion
Herein are reported the synthesis and electrochemical
behaviour of a new series of molecules in which electronically
active ligands have been attached to the amino groups of the
tren moiety. This functionalisation of the secondary amines
of the cap should affect the interaction with dioxygen. The
interest of such a derivatisation is that it modifies the electronic
properties of the copper chelate, without any modification of
the basic backbone, the steric hindrance or the relative position
of the two metals.
Three molecules have been synthesised and these differ only
by the N-substitution of the tren amino functions bearing
either a tribenzyl, a tris[4-(dimethylamino)benzyl], or a tris(4-
nitrobenzyl) group. These benzyl moieties should have different
electronic effects on the copper ion in the distal position and,
consequently, modify the electron density of the bound O2.
Since it has been previously demonstrated that a nitrogen base
covalently bound to the porphyrin is not critical for the effi-
ciency of the catalyst,8,13 1,2-dimethylimidazole (1,2-diMeIm)
was simply added as the fifth ligand of iron in the present study.
The synthesis of the iron five-coordinate complexes and hetero-
bimetallic iron–copper catalysts is depicted in Scheme 1.
1 and 2 have been synthesised by grafting the corresponding
trisubstituted trens 6 and 7 on the three acryloyl pickets of
porphyrin 5 under mild conditions.14 In model molecule 2, the
secondary amine groups are functionalised by an electron
donor substituent (X = NMe2).† Unfortunately, attempts
towards synthesis of a compound possessing an electron-
withdrawing substituent (X = NO2) failed, plausibly, because of
the lower nucleophilicity of the amine. Actually, the prepar-
ation of 3† required the reaction of p-nitrobenzyl bromide,
under more drastic conditions, on the tren-capped porphyrin 4,
the synthesis of which has been previously reported.7
The electroreduction of dioxygen was examined by rotating
ring-disk voltammetry (RRDE).‡ The iron-only complexes
corresponding to 1 (Fig. 1) and 2 (Fig. 2, dashed line) are
efficient catalysts of the 4eϪ reduction when adsorbed on the
graphite electrode, in contact with an aqueous solution at pH =
6.86. This is similar to what has been oberved for other model
Binding of the Cu centre to the oxygen–iron porphyrin com-
plex could possibly be dependent on the coordination sphere of
the metal. Various nitrogenous ligands (triazacyclononane,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 7 4 – 1 2 7 6
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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Fig. 2 RRDE voltammograms of FeCu complexes 1 (b), 2 (d) and
3 (c) and of Fe complex 2Fe (dЈ) for comparison. a: bare graphite
electrode.
electrode with the aqueous solution; 3Fe is somewhat soluble
in water.
As shown in Fig. 1, 1Fe is almost a selective catalyst for the
4eϪ reduction of dioxygen (curve b). The number of electrons
exchanged per O2 molecule has been derived from the limiting
current on the bare graphite electrode (curve a). The pro-
duction of hydrogen peroxide at the platinum ring is very low
when the limiting current of the reduction process is reached.
Some hydrogen peroxide is produced in the activation region
of the O2 reduction process, at the foot of the wave; this has
been observed in our previous work7,8 and is also apparent
in the results reported by others.9 The 4eϪ reduction process
takes over at larger overpotentials. The reduction starts
at a much more positive value (ϩ0.05 V) than those corre-
sponding to various compounds we have previously studied.7
From successive potential scans (Fig. 1), it appears that the
catalyst is not stable, consequently preventing Koutecky–Levich
analysis. Along its degradation, the wave shifts to more negative
potentials and the reduction current decreases, which is attrib-
uted to the diminution of the surface concentration of the
catalyst.
Scheme 1 Synthesis of substituted tren-capped porphyrins. Reagents:
i, tren, 6 or 7, MeOH–CHCl3, 50 ЊC; ii, p-nitrobromobenzyl, DMF,
90 ЊC; iii, iron bromide, THF, 55 ЊC; iv, copper bromide, CH3OH, 80 ЊC;
v, excess of 1,2-diMeIm.
The FeCu nitro-derivative complex 3FeCu does not exhibit a
catalytic activity (Fig. 2, curve c), probably for the same reasons
as those mentioned above for 3Fe. 1FeCu exhibits a poor
catalytic activity, forming almost exclusively hydrogen peroxide;
the reduction of dioxygen begins at a potential only slightly
more positive than that on the graphite surface. 2FeCu, the
complex bearing NMe2 electrodonor groups, has a modest
catalytic activity towards O2 reduction with respect to its
reduction potential; the reduction starts at about Ϫ0.05 V, the
plateau being reached at Ϫ0.4 V (Fig. 2, d). However, it induces
mainly the four electron reduction of dioxygen to water. This
has to be pointed out as, from the various PFeCu and PFe
examined, 2FeCu is the first heterodinuclear compound having
a catalytic efficiency equivalent to that of the iron-only com-
plex, 2Fe.
Fig. 1 Catalysis of O2 reduction by 1Fe. a: bare graphite electrode;
b, c, d, e: four consecutive cycles after adsorption of 1Fe on the graphite
disc of the RRDE.
molecules.7 After adsorption of 3Fe at the electrode, the
voltammogram is equivalent to that observed for the bare
graphite electrode; one notices exclusively the 2eϪ reduction of
O2. This could result from a very low concentration of 3Fe at
the surface of graphite due to leaching from the contact of the
Conclusions
A new series of tren-capped porphyrins has been prepared
and studied both as their iron and iron–copper complexes.
Slight modifications of the electronic properties in the distal
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 7 4 – 1 2 7 6
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3: 1H NMR δH (500 MHz, CDCl3, 323 K): δ = 9.48 (s, 1H, –NHCO),
9.04 (d, 2H, J = 5.0 Hz, Hβpyr), 9.00 (d, 2H, J = 5.0 Hz, Hβpyr), 8.97 (s,
2H, –NHCO), 8.94 (d, 2H, J = 5.0 Hz, Hβpyr), 8.79 (d, 2H, J = 5.0 Hz,
coordination site have been achieved through the substitution
of the para hydrogen atom by NMe2 and NO2 groups. The
results indicate that closely related catalysts can influence very
differently the reduction of dioxygen. For instance, in this
new series, only one of the bimetallic complexes is a selective
4eϪ catalyst. Indeed, in the case of the –NMe2 substituent, the
copper might be in a suitable electronic environment to interact
properly with the iron-bound O2 in such a way that the cleavage
of the O–O bond occurs. The adsorption of these molecules
could also be affected by as light structural modifications as
those performed in this work. These results confirm that, for
synthetic molecules adsorbed at the surface of an electrode, the
presence of a copper center does not improve the catalysis in
comparison with iron-only analogues.
These observations demonstrate the fact that precise com-
parisons should be performed only between very closely related
structures. Besides, in order to examine the influence of the
Tyr244 motif, a third generation of tren-capped catalysts is
under investigation. In this series, both the location and the
properties of the group mimicking the tyrosine will be
modulated.
Hβpyr), 8.46 (d, 2H, J = 8.0 Hz, Haro), 8.22 (d, 1H, J = 8.0 Hz, Haro), 8.03
(d, 2H, J = 9.0 Hz, Haro), 7.93 (d, 4H, J = 9.0 Hz, Haro), 7.91–7.79
(m, 6H, Haro), 7.67 (dd, 1H, Jo = 7.5 Hz, Jm = 1.5 Hz, Haro), 7.63–7.53
(m, 3H, Haro), 7.51 (td, 1H, Jo = 7.5 Hz, Jm = 1.0 Hz, Haro), 7.37 (t, 1H,
J = 7.5 Hz, Haro), 7.00 (d, 2H, J = 8.5 Hz, Haro), 6.73 (d, 4H, J = 8.5 Hz,
Haro), 6.39 (s, 1H, –NHCO), 2.25 (d, 2H, J = 22.5 Hz), 2.10–2.00 (m,
4H), 1.98–1.89 (m, 4H), 1.86–1.74 (m, 4H), 1.62 (m, 2H), 1.53 (s, 2H),
1.19 (s, 3H), 0.57 (m, 2H), 0.08 (m, 2H), Ϫ0.05 (m, 2H), Ϫ1.36 (m, 2H),
Ϫ1.83 (m, 2H), Ϫ1.99 (m, 2H), Ϫ2.49 (s, 2H, ϪNHpyr). Anal. Calcd. for
C82H75N15O10ؒ2CHCl3: C, 59.79, H, 4.72, N, 12.45, Found: C, 59.34, H,
4.84, N, 12.44%. 3Fe: MS (FAB): m/z = 1484.6 [M]ϩ. 3FeCu: HR-MS
(LSI-MS): calcd. m/z = 1484.5092 for C82H74N15O4Fe [M Ϫ (CuBr) ϩ
H]ϩ, Found 1484.5088.
‡ The diameter of the highly oriented graphite electrode (edge plane:
EPGE) disk is 6 mm, the collecting efficiency of the ring-disk electrode
being 27% (Pine Instrument Co.). The graphite electrode is modified
by dipping it 5 minutes in the solution of the catalyst in CHCl3. A bi-
potentiostat (Solea-Tacussel) pilots the disk potential, when the
platinum ring is maintained at 0.8 V vs. SCE for experiments at
pH 6.86 (KH2PO4 0.025 M ϩ Na2HPO4 0.025 M).
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Notes and references
† Selected data for 1: 1H NMR δH (500 MHz, CDCl3, 323 K): δ = 10.13
(s, 1H, –NHCO), 9.67 (s, 2H, –NHCO), 9.02 (d, J = 5.0 Hz, 2H, Hβ-pyr),
8.99 (d, J = 5.0 Hz, 2H, Hβ-pyr), 8.92 (d, J = 5.0 Hz, 2H, Hβ-pyr), 8.71 (d,
J = 5.0 Hz, 2H, Hβ-pyr), 8.37 (d, J = 8.5 Hz, 2H, Haro), 8.18 (d, J = 8.0 Hz,
1H, Haro), 7.86–7.76 (m, 8H, Haro), 7.51 (td, J = 7.5 Hz, J = 1.0 Hz, 4H,
Haro), 7.43 (td, J = 7.5 Hz, J = 1.0 Hz, 2H, Haro), 7.23–7.16 (m, 4H),
7.13 (m, 5H), 6.82 (d, J = 7.0 Hz, 3H, Haro), 6.67 (m, 3H), 2.82 (d, J =
20.0 Hz, 4H, –CH2 benzyl), 2.41 (d, J = 15.0 Hz, 2H, –CH2 benzyl), 2.02–
1.63 (m, 12H, –CH2), 1.31 (s, 3H, –CH3), 0.56 (m, 2H), Ϫ0.06 (m, 4H),
Ϫ1.58 (m, 4H), Ϫ2.10 (m, 2H), Ϫ2.48 (s, 2H, –NHpyr). Anal. Calcd. for
C82H78N12O4ؒH2O: C, 74.98, H, 6.14, N, 12.80, Found: C, 75.03, H,
6.01, N, 12.62%; 1Fe: MS (MALDI-TOF, linear mode): m/z (%):
1348.96 (100) [Mϩ]. 1FeCu: MS (FAB): m/z = 1349.55 [M Ϫ (CuBr) ϩ
H]ϩ.
2: 1H NMR δH (500 MHz, CDCl3, 323 K): δ = 10.36 (s, 1H, –NHCO),
10.05 (s, 2H, –NHCO), 8.97 (d, 2H, J = 5.0 Hz, Hβpyr), 8.93 (d, 2H, J =
5.0 Hz, Hβpyr), 8.87 (d, 2H, J = 5.0 Hz, Hβpyr), 8.66 (d, 2H, J = 5.0 Hz,
10 S. Yoshikawa, K. Shinzawa-Itoh, R. Nakashima, R. Yaono,
E. Yamashita, N. Inoue, M. Yao, M. J. Fei, C. P. Libeu,
T. Mizushima, H. Yamaguchi, T. Tomizaki and T. Tsukihara,
Science, 1998, 280, 1723.
H
βpyr), 8.34 (d, 2H, J = 8.0 Hz, Haro), 8.02 (d, 1H, J = 8.0 Hz, Haro), 7.83–
7.70 (m, 6H), 7.72 (td, 1H, Jo = 8.5 Hz, Jm = 1.5 Hz, Haro), 7.50 (m, 4H,
Haro), 7.39 (td, 1H, Jo = 7.0 Hz, Jm = 1.0 Hz, Haro), 6.67 (d, 2H, J =
8.0 Hz, Haro), 6.49–6.40 (m, 10H), 5.30 (s, 1H, –NHCO), 2.92 (s, 6H,
–CH3), 2.83 (s, 9H, –CH3), 2.69 (m, 4H, –CH2benzyl), 2.28 (d, 2H, J =
13.5 Hz, –CH2benzyl), 2.15–1.70 (m, 12H, 2CH2benzyl ϩ 2CH3), 1.59 (m,
6H, –CH2benzyl), 0.49 (m, 2H, –CH2benzyl), Ϫ0.25 (m, 4H, –CH2benzyl),
Ϫ1.55 (m, 4H, –CH2benzyl), Ϫ2.08 (m, 2H, –CH2benzyl), Ϫ2.56 (s, 2H,
–NHpyr). Anal. Calcd. for C88H93N15O4ؒCH2Cl2: C, 70.81, H, 6.64, N,
13.92, Found: C, 70.44, H, 6.32, N, 11.91%; 2Fe: MS (MALDI-TOF):
m/z = 1477.9 [M]ϩ. 2FeCu: MS (MALDI-TOF): m/z = 1478.7 [M Ϫ
(CuBr) ϩ H]ϩ.
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O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 2 7 4 – 1 2 7 6
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