Inserting a hydrogen-bond relay between proton exchanging sites in proton-coupled electron transfers

Article abstract of DOI:10.1002/anie.200907192

(Figure Presented) Take the "H-bond" train: Introduction of a hydrogen-bond relay efficiently mediates the electron-transfer triggered exchange of protons between two sites over large distances (see picture). Thanks to this concerted proton-electron trans

Full text of DOI:10.1002/anie.200907192

Angewandte
Chemie
DOI: 10.1002/anie.200907192
Concerted Proton–Electron Transfer
Inserting a Hydrogen-Bond Relay between Proton Exchanging Sites in
Proton-Coupled Electron Transfers**
Cyrille Costentin, Marc Robert, Jean-Michel Savꢀant,* and Cꢀdric Tard
Long-distance electron[1] and proton transfer (or transport)[2]
are key processes in a considerable number of natural
systems. When electron- and proton-transfer processes are
coupled and involve different sites (proton-coupled electron
transfer (PCET) reactions),[3] the occurrence of concerted
proton–electron transfer (CPET) reactions usually require
the presence of a hydrogen bond between the proton borne by
the group being oxidized and the proton acceptor (and
vice versa for a reduction process), as is appears to be the case
in emblematic systems such as photosystem II[4] and ribonu-
cleotide reductase.[5] The distances over which the proton may
travel as the result of a CPET reaction are limited to values
that usually induce the formation of a hydrogen bond in the
starting molecule.
Herein we explore the idea according to which this
distance might be substantially increased by inserting a
hydrogen-bond relay between the group being oxidized and
the distant proton acceptor as represented in Scheme 1.[6a,b]
The relay is a group bearing a hydrogen atom, able to accept a
hydrogen bond from the moiety being oxidized and, at the
same time, able to form a hydrogen bond with the proton
accepting group without going through a protonated state in
the course of the reaction.
the role sometimes invoked of water molecules in PCET
reactions.[7] The molecule in Scheme 1 does not retain the
properties of chains of water molecules engaged in a
Grotthuss-type transport of a proton,[8] however the OH
group possesses the basic property of water molecules in that
it is both a hydrogen-bond acceptor and donor.
To test the occurrence of the reaction depicted in
Scheme 1 we chose to use the electrochemical approach for
the PCET reactions[3b,9] rather than the homogeneous
approach. The main reason for this choice of nondestructive
electrochemical techniques, such as cyclic voltammetry meas-
urements,[10] is the quick investigation of a continuous range
of driving forces that leads to the determination of a standard
rate constant (rate constant at zero driving force). The main
features of the typical cyclic voltammogram shown in
Figure 1a are a one-electron stoichiometry (determined
from the peak height) and chemical reversibility, thus
indicating that the cation radical 2a resulting from oxidation
is stable on the cyclic voltammetric time scale. Species 2a is
actually stable for longer periods of time as revealed by
preparative-scale electrolysis[6c] at 1.34 V vs. NHE. These
results confirmed the one-electron stoichiometry and the
formation of the expected radical cation 2a, which is
characterized by a typical UV/Vis spectrum for a phenoxyl
radical species[11] (l: 389, 407, 645 nm; e: 1507, 1549,
164 Lcmꢀ1 molꢀ1). The infrared spectrum of 2a shows the
depletion of a band at 1631 cmꢀ1 corresponding to a C C
=
=
vibration of the pyridine moiety (the second pyridine C C
band is hidden by the supporting electrolyte). The same
evolution was observed upon protonation of 2,4,6-trimethyl
pyridine (band at 1633 cmꢀ1), thus confirming that the
pyridine moiety is protonated upon generation of the
phenoxyl radical species.
Scheme 1.
The reversibility and one-electron stoichiometry of the
cyclic voltammetric response shown in Figure 1a contrasts
with the irreversibility and two-electron stoichiometry
observed when neither the pyridine acceptor, nor the OH
relay are present as with 2,4,6-tri-tert-butyl phenol (1c;
Figure 1c). For 1c,[12] the cation radical that was initially
generated rapidly and irreversibly deprotonates, and the
resulting phenoxyl radical is oxidized more easily than the
starting phenol according to an ECE mechanism,[10] thus
resulting in a two-electron stoichiometry. The same behavior
is also observed in the presence of the OH relay and in the
absence of the pyridine moiety (Figure 1d; the synthesis of 1d
is described in the Supporting Information). It also follows
that the reversible oxidation of 1a does not proceed through
the intermediacy of the cation radical bearing a positive
charge on the central OH group.
Although other moieties could play a similar function, we
have selected an OH group for this purpose—having in mind
[*] Prof. Dr. C. Costentin, Prof. Dr. M. Robert, Prof. Dr. J.-M. Savꢀant,
Dr. C. Tard
Laboratoire d’Electrochimie Molꢀculaire, Unitꢀ Mixte de
Recherche Universitꢀ – CNRS No 7591, Universitꢀ Paris
Diderot, Bꢁtiment Lavoisier
15 rue Jean de Baꢂf, 75205 Paris Cedex 13 (France)
E-mail: saveant@univ-paris-diderot.fr
[**] Financial support from the Agence Nationale de la Recherche
(Programme blanc PROTOCOLE) is gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200907192.
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ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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the direct formation of a hydrogen bond between them. The
X-ray structure of 1a[6b] (Figure 2) shows that this is indeed
the case—the distance between the phenolic oxygen atom and
Figure 2. X-ray structure[6] of 1a and DFT calculations[10] for 1a and 2a.
the nitrogen atom of pyridine is indeed 4.44 ꢀ and the O2-
O1-C1-N1 dihedral angle is 113.98. The DFT calculations[6c]
led to a very similar result in the case of 1a (Figure 2) and also
showed that substantial folding does not take place in cation
radical 2a.
Another interesting observation is that of the existence of
an H/D kinetic isotope effect (KIE) for 1a—similar to what
was observed with 1b (see Table 1)—thus pointing to the
occurrence of a concerted pathway indicating that the
equilibrium shown in Scheme 1 is not merely the expression
of a global process but should be viewed as an elementary
CPET step. This conclusion also falls in line with the
implausibility of a mechanism that would proceed through
oxidation of the zwitterionic form (1az) of 1a, owing to the
small equilibrium ratio [1az]/[1a] ꢁ 10ꢀ9.[15] Also, the fact that
the reaction does not proceed via an intermediate in which
the central OH group is protonated is in agreement with the
pKa values of phenol (pKa = 27)[15a] and protonated alcohol
(pKa < 2)[15d] in acetonitrile.
Figure 1. Cyclic voltammetry measurements in acetonitrile + 0.1m
nBu4NBF4 for 1 mm of compound at a glassy carbon electrode and at
a scan rate of 0.2 Vsꢀ1. In the scan of 1a, the solid and dashed
traces were recorded in the presence of 1% CH3OH or CD3OD,
respectively.
The cyclic voltammetric response of 1a (Figure 1a)
resembles more that of the aminophenol 1b (Figure 1b) in
terms of both electron stoichiometry and chemical reversi-
bility, although the anodic-to-cathodic potential separation is
larger in the first case than in the second. As shown
earlier,[13,14] with 1b, the proton generated upon one-electron
oxidation of the phenol moiety is transferred to the amine
group concertedly with electron transfer thanks to a six-
membered ring configuration, which is favorable to the
formation of a hydrogen bond between the phenol and
amine group in the starting molecule. In the case of 1a, proof
that the alcoholic OH group effectively serves as a hydrogen-
bond relay between the phenol and pyridine groups requires
that the molecule is not folded so as to put these two groups at
a sufficiently short distance from one another to bring about
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Chemie
In the framework of the CPET mechanism, we derive the
standard rate constant of the reaction (kS) from the peak
separation in Figure 1a, after linearization of the Marcus–
Hush–Levich activation-driving force law, thus leading to the
Butler–Volmer rate law[6c,13b] with a transfer coefficient equal
to 0.5 [Eq. (1)]; where i: current, S: electrode surface area,
[]: concentrations at the electrode surface, E: electrode
potential, E0: CPET standard potential. The standard rate
constant of the reaction (kS), that is, the rate constant at zero
driving force, is a measure of the intrinsic characteristics of
the reaction.
constant for 1a should therefore be marginally slower than for
1b.
We may thus conclude that the introduction of a hydrogen
bonding group between the electron and proton exchanging
sites may offer an efficient route for proton movement over
´
˚
distances as large as 4.3 A, by means of the translocation of
two protons in a concerted manner with electron transfer.
This Grotthuss-type proton transfer is as efficient as the travel
a proton accomplishes over distances of the order of 2.5 ꢀ in
systems where hydrogen bonding between the phenol moiety
and the proton acceptor benefits from the formation of a six-
membered ring. The key feature of this efficient proton
movement is a “hydrogen-bond swing” as the one shown in
Scheme 1, which avoids going through a high-energy inter-
mediate in which the relay would be protonated. The ability
of the trifluoro-substituted alcohol group to serve as an
efficient relay is presumably the result of a good balance
between its hydrogen-bond-accepting and -donating capabil-
ities.
ꢂ
ꢃꢄ
ꢂ
ꢃ
ꢅ
ꢀ
ꢁ
ꢀ
ꢁ
i
F
2RT
ꢀF
¼ kS exp
E ꢀ E0
½1ꢂ ꢀ exp
E ꢀ E0 ½2ꢂ
ð1Þ
FS
RT
It is immediately clear that with 1a, a scan rate of only
0.2 Vsꢀ1 is sufficient for the peak separation to be controlled
by the CPET kinetics (Figure 1a). Whereas at this scan rate,
the oxidation of 1b is still controlled by diffusion (Figure 1b).
For 1b, one has to operate at a scan rate of 5 Vsꢀ1 to reach the
CPET kinetic control to achieve good peak separation.[13]
Table 1 summarizes the values of kS obtained by using, as the
Work is in progress to further investigate the mechanism
of the hydrogen-bond relay and to uncover the parameters
that constitute a good relay.
Received: December 21, 2009
Published online: April 20, 2010
Table 1: Characteristics of the CPET oxidation of 1a and 1b.
Compound
E0
kS,H
KIE
l
l0
li
[VNHEꢀ1
]
[cmsꢀ1
]
[eV]
[eV]
[eV]
Keywords: electrochemistry · electron transfer· hydrogenbonds·
phenols · proton transfer
.
1a
1.10
0.85
5ꢃ10ꢀ4
8ꢃ10ꢀ3
2.4
1.7
1.36
1.06
0.78
0.78
0.58
0.28
1b[13]
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diffusion coefficient the value derived from the peak heights
(10ꢀ5 cm2 sꢀ1), together with the values of the standard
potential. Comparison between the values of kS in the
presence of 1% of CH3OH or CD3OD allowed the determi-
nation of the H/D kinetic isotope effects reported in Table 1
(upon introduction of 1% of CD3OD, the NMR proton
signals for phenol and alcohol disappeared therefore indicat-
ing complete deuteration).
With such a small KIE and assuming that electron transfer
is adiabatic,[13b] the preexponential factor (Z) in the expres-
sion of the standard rate constant (as illustrated experimen-
tally by the temperature dependent kinetics of the oxidation
of 1b[13b]) [Eq. (2)][10,13c] can be approximated by the collision
h
ꢆ
ꢇ i
2
rffiffiffiffiffiffiffiffi
1
RT
4l
l
Z
exp ꢀ
RT ꢀ j
RT
ð2Þ
kS ¼ Z
dj
4pl ꢀ1
1 þ expðjÞ
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
frequency, Z ¼ RT=2pM (M: molar mass, M =
423 gmolꢀ1), thus leading to a numerical estimation of the
experimental reorganization energy, l = 1.36 eV for 1a, to be
compared with l = 1.06 eV for 1b. The solvent reorganization
energy (l0) has been estimated to be 0.78 eV for 1b, and is
likely to be the same for 1a. It follows that the internal
reorganization energy varies from 0.28 to 0.58 eV from 1b to
1a. With a more rigid structure, in which the movements of
the heavy atoms would be minimized, the standard rate
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Angew. Chem. Int. Ed. 2010, 49, 3803 –3806
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3805

Communications
[14] a) homogenous oxidation of similar aminophenols has also been
idine in water (7.43 and 6.99, respectively).[15c] The pKa value
used for the pyridine in 1a was the average value for 2,4,6-
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H. Nagao, A. G. DiPasquale, O. P. Lam, M. A. Lockwood, K.
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ꢆ
ꢇ
pKPhOH ꢀpK2;4;6ꢀtimethylpyridine þpK2;4ꢀdimethylpyridine
½1azꢂ
2
[15] a)
ꢁ 10ꢀ
ꢁ 10ꢀ9
,
½1aꢂ
approximated by extrapolation and interpolation from the
pKa values of pyridine and phenol in acetonitrile (12.3 and 27,
respectively)[15b] and in water (5.2 and 10, respectively),[15c] and
the pKa values for 2,4,6-trimethylpyridine and 2,4-dimethylpyr-
[16] Other approaches are possible, see for example: S. Hammes-
Schiffer, A. V. Soudackov, J. Phys. Chem. B 2008, 112, 14108 –
14123.
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Angew. Chem. Int. Ed. 2010, 49, 3803 –3806