Proton switch for modulating oxygen reduction by a copper electrocatalyst embedded in a hybrid bilayer membrane

Article abstract of DOI:10.1038/nmat3974

Molecular switches gate many fundamental processes in natural and artificial systems. Here, we report the development of an electrochemical platform in which a proton carrier switches the activity of a catalyst. By incorporating an alkyl phosphate in the lipid layer of a hybrid bilayer membrane, we regulate proton transport to a Cu-based molecular oxygen reduction reaction catalyst. To construct this hybrid bilayer membrane system, we prepare an example of a synthetic Cu oxygen reduction reaction catalyst that forms a self-assembled monolayer on Au surfaces. We then embed this Cu catalyst inside a hybrid bilayer membrane by depositing a monolayer of lipid on the self-assembled monolayer. We envisage that this electrochemical system can give a unique mechanistic insight not only into the oxygen reduction reaction, but into proton-coupled electron transfer in general.

Full text of DOI:10.1038/nmat3974

ARTICLES
PUBLISHED ONLINE: 11 MAY 2014 | DOI: 10.1038/NMAT3974
Proton switch for modulating oxygen reduction by
a copper electrocatalyst embedded in a hybrid
bilayer membrane
Christopher J. Barile1†, Edmund C. M. Tse1†, Ying Li1, Thomas B. Sobyra1, Steven C. Zimmerman1,
Ali Hosseini2 and Andrew A. Gewirth1,3
*
Molecular switches gate many fundamental processes in natural and artificial systems. Here, we report the development of an
electrochemical platform in which a proton carrier switches the activity of a catalyst. By incorporating an alkyl phosphate
in the lipid layer of a hybrid bilayer membrane, we regulate proton transport to a Cu-based molecular oxygen reduction
reaction catalyst. To construct this hybrid bilayer membrane system, we prepare an example of a synthetic Cu oxygen reduction
reaction catalyst that forms a self-assembled monolayer on Au surfaces. We then embed this Cu catalyst inside a hybrid bilayer
membrane by depositing a monolayer of lipid on the self-assembled monolayer. We envisage that this electrochemical system
can give a unique mechanistic insight not only into the oxygen reduction reaction, but into proton-coupled electron transfer
in general.
H
olecular switches regulate many functions in biology,
N
N
TFA, Et3SiH, EtOH
Room temperature
chemistry and physics, and the development of artificial
switches is an important goal in these fields. In
Ph3CS
N
H
N
H
N
M
nanotechnology, chemical switches are used in the construction
of molecular machines1,2 and computers3,4. In biological systems,
switches are fundamental to gene regulation5, vision6 and cellular
trafficking7. Frequently, such biological switches modulate proton
transfer occurring in enzymes and across cellular membranes8.
The protons regulated by these switches are frequently involved in
proton-coupled electron transfer (PCET) reactions.
H
N
N
HS
N
H
N
H
N
BTT
PCET reactions are also fundamental to many energy conversion
Figure 1 | Synthesis of BTT.
processes such as N2 fixation, H2O oxidation and CO2 reduction9–12
.
The four-electron four-proton oxygen reduction reaction (ORR) to
water is one of the most intensely studied reactions involving PCET
(ref. 13). Much experimental and computational work examines the
mechanism of the ORR in an effort to construct more efficient fuel
cell cathodes13. However, in many cases, the mechanism of the ORR
remains poorly understood.
In this paper, we design and prepare a robust, active, dinuclear
Cu ORR catalyst specifically tailored to be embedded inside a
HBM system. We demonstrate that proton delivery to the catalyst
through the lipid layer can be controlled through the use of an alkyl
phosphate proton carrier and explore how this proton carrier can be
used as a pH-sensitive switch.
At present, as proton transfer is hard to switch on and off, the
effect of proton transfer on catalysis and other reactions cannot be
Ligand design and synthesis
easily evaluated. Traditionally, the pH of the bulk solution is varied We designed a new ligand to support an active Cu O2 reduction
to affect the thermodynamics of redox couples in the catalyst11,14–16
.
catalyst in a HBM system. Figure 1 and Supplementary Fig. 1
The accompanying redox shift, however, gives little information illustrate the preparation of 6-((3-(benzylamino)-1,2,4-triazol-5-
about the influence of proton flux on the mechanism of the catalytic yl)amino)hexane-1-thiol (BTT). The BTT ligand features three
process. The role of covalently bound proton relays in ORR catalysts active regions, each with a specific function. The Cu coordination
has also been explored17–19. A hybrid bilayer membrane (HBM) is site is based on 3,5-diamino-1,2,4-triazole (DAT), which on
a unique electrochemical platform that can be used to interrogate coordination to Cu forms an efficient O2 reduction catalyst over a
the role of proton flux on a molecular ORR catalyst without altering wide pH range25.
either its molecular structure or the contents of the bulk solution20.
The second feature of BTT is a terminal benzyl moiety. Our initial
In a HBM system, a monolayer of lipid molecules is appended attempts to deposit a lipid layer on a hydrophilic amino-terminated
to a self-assembled monolayer (SAM) of alkanethiols covalently ligand were unsuccessful. We hypothesized that unfavourable
attached to a Au electrode21–24. The role of proton flux in affecting the interactions between the hydrophilic ends of the amino-terminated
reactivity of a molecular ORR catalyst remains largely unexplored.
ligand and the hydrophobic tails of the lipid hinder the formation
1Department of Chemistry, University of Illinois at Urbana–Champaign, Urbana, Illinois 61801, USA, 2Department of Chemical and Materials Engineering,
The University of Auckland, Auckland 1010, New Zealand, 3International Institute for Carbon Neutral Energy Research (WPI-I2CNER), Kyushu University,
Fukuoka 812-8581, Japan. †These authors contributed equally to this work. *e-mail: agewirth@illinois.edu
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NATURE MATERIALS DOI: 10.1038/NMAT3974
ARTICLES
N+
O
−O
O
O
O
P
O
11
O
H
N
O
H
N
H
N
11
9
S
S
5
5
N
Cu2+
N
N
O
−(ClO4)4
Cu2+
O− K+
P
Au
O
OH
N
N
H
N
H
N
H
N+
O
O
−O
O
O
O
P
O
11
O
11
Figure 2 | Schematic of the hybrid bilayer membrane. The HBM used in this study is composed of the Cu complex of BTT (blue), the
1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid layer (red), and the alkyl phosphate proton carrier (green).
of a HBM in this case. Therefore, we attached a hydrophobic benzyl and DAT both exhibit redox waves at similar potentials in
moiety onto BTT to append the lipid layer, allowing us to construct an ethanolic solution, further supporting this hypothesis
the electrochemical platform described in Fig. 2.
(Supplementary Fig. 7). On the formation of the Cu complex
Finally, we equipped BTT with a hexylthiol chain to allow on the BTT-Au surface, the charge under the redox wave nearly
the formation of a well-packed SAM on Au electrodes. Electron doubles (Supplementary Fig. 6, blue curve). This reflects an
transfer through this short-chained thiol is facile, eliminating it additional one-electron Cu(I)/Cu(II) couple occurring at a
as the rate-limiting step for O2 reduction26. A full monolayer of similar potential to the free BTT-Au wave. By correcting for the
BTT on Au electrodes was formed through the in situ deprotection contribution of the BTT, the surface coverage of the Cu complex
of the tritylated thiol using trifluoroacetic acid and triethylsilane of BTT on Au is 3.4×10−11 mol cm−2, which is similar to the value
(Fig. 1; ref. 27). O2 reduction on the BTT-Au surface is greatly expected for a full monolayer (Supplementary Note 5). We note that
suppressed compared to a bare Au surface, demonstrating that the the O2 reduction onset potential of Cu BTT on Au is about 300 mV
SAM layer is well formed and effectively passivates the Au electrode more negative than the Cu(I)/Cu(II) couple. This is expected as O2
(Supplementary Fig. 2).
reduction is an inhibited process involving multiple proton delivery,
electron transfer, and binding steps.
Oxygen reduction catalysis
To form an active O2 reduction catalyst, we subsequently immersed
Hybrid bilayer membrane construction
the BTT-Au surface in a solution of Cu(ClO4)2 to form a dinuclear To construct a platform containing a molecular switch, we
Cu complex with two triazole units. Scanning tunneling microscopy embedded the catalyst in a lipid layer composed of 1,2-dimyristoyl-
(STM) reveals that the roughness of the bare Au and BTT-Au sn-glycero-3-phosphocholine (DMPC), which is stable in the
surfaces with and without Cu do not deviate significantly, suggesting pH 5–7 range, to form a HBM. Ellipsometric measurements
that the BTT monolayer is well packed and its uniformity is demonstrate that the length of the appended lipid layer is
not perturbed by the addition of Cu (Supplementary Fig. 3). 21Å (Supplementary Fig. 4), and the double-layer current of
Ellipsometric measurements are also consistent with the formation the electrode decreases on formation of the HBM. These two
of a full monolayer, as the length of the Cu complex of BTT on Au is findings are consistent with the formation of a well-formed DMPC
21 Å, comparable to the value obtained from theoretical modelling monolayer (Supplementary Fig. 8; ref. 29). Supplementary Fig. 8 also
of the SAM (Supplementary Fig. 4).
shows that the amount of charge under the BTT and Cu(I)/Cu(II)
O2 reduction by the Cu complex of BTT on Au shows an onset waves decreases substantially on HBM formation. This behaviour
potential of −70 mV versus Ag/AgCl at pH 7 (Fig. 3, blue curve). arises because the anions (H2PO−4 /HPO2−) from the aqueous–lipid
The Cu complex of BTT on Au reduces O2 by an average of 3.7±0.2 interface are slow to diffuse through the4lipid layer and compensate
electrons, whereas a bare Au surface reduces O2 by an average of for the positive charge on the Cu complex, consistent with
2.9±0.1 electrons (Supplementary Fig. 5). The number of electrons previous studies examining the transport properties of anions in
by which O2 is reduced and the onset potential of the Cu complex of HBM systems29,30
.
BTT are similar to the values reported for the Cu complex of DAT
At pH 7, the addition of a lipid layer to the Cu complex shifts
on carbon black25. These observations demonstrate that modifying the onset potential for O2 reduction ∼300 mV negative relative to
the Cu complex of DAT with alkylthiol and benzyl moieties does not the onset of the Cu complex without lipid, significantly decreasing
perturb its catalytic activity.
the catalytic current (Fig. 3, red curve). We hypothesize that the
Under an argon atmosphere, the BTT-Au surface in the absence observed negative shift in the O2 reduction onset potential is due
of Cu is redox-active (Supplementary Fig. 6, black curve). We to a change in the local environment of the catalyst from an aqueous
hypothesize that this is due to the reversible one-electron reduction medium to the hydrophobic lipid interior. O2 reduction in the HBM
of the triazole ring, which has been reported for other triazole is not limited by the diffusion of O2 in DMPC because the diffusion
derivatives28. Protected BTT (Supplementary Fig. 1, compound 4) coefficients of O2 in DMPC and pH 7 buffer are comparable at
2
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NATURE MATERIALS DOI: 10.1038/NMAT3974
ARTICLES
0
−100
−200
0
−100
−200
−300
−0.50
−0.25
Potential versus Ag/AgCl/V
0.00
−0.50
−0.25
0.00
Potential versus Ag/AgCl/V
Figure 4 | pH 5 voltammetry. Linear sweep voltammograms of O2
reduction by a SAM of the Cu complex at 26 ◦C (blue), the HBM containing
the Cu complex with DMPC only in the lipid layer at 26 ◦C (red), and the
HBM containing the Cu complex with one equivalent of MDP incorporated
in the lipid layer at 26 ◦C (green) and 10 ◦C (purple) on Au in pH 5 buꢀer
Figure 3 | pH 7 voltammetry. Linear sweep voltammograms of O2
reduction by a SAM of the Cu complex of BTT (blue), the HBM containing
the Cu complex with DMPC only in the lipid layer (red), the HBM
containing the Cu complex with one equivalent of MDP incorporated in the
lipid layer (green), and a BTT SAM (black) on Au at 26 ◦C in pH 7 buꢀer
solution at a scan rate of 10 mV s−1
.
solution at a scan rate of 10 mV s−1
.
is energetically unfavourable34. However, at pH 5, MDP exists
room temperature31–33. Therefore, O2 is expected to readily permeate predominantly as RHPO−4 . This species can then be protonated to
through the lipid layer (Supplementary Note 6). give neutral RH2PO4, which can facilitate proton transport across
There are two remaining possibilities as to the origin of the the lipid layer of the HBM. This is confirmed by an increased O2
decreased O2 reduction rate in the HBM. These relate to inefficient reduction current by the embedded catalyst at pH 5 when one
delivery of either protons or electrons to the catalyst. The Cu equivalent of MDP is incorporated in the lipid layer of the HBM
complex of BTT without a lipid layer exhibits facile O2 reduction, (Fig. 4, green curve).
suggesting that electron delivery from the Au electrode is not rate
We hypothesize that the presence of MDP in the lipid layer
determining in the HBM. Unlike O2, however, protons do not readily increases the rate of proton delivery to the catalyst. Although the
diffuse through the lipid layer of the HBM. In biological systems, O2 reduction current increases, it is not revived to the amount
protons are only shuttled across lipid bilayers with the aid of specific observed for the Cu complex of BTT without lipid because O2
channels or mediators34. This suggests that sluggish proton transfer reduction inside the HBM is still limited by proton transport.
through the lipid layer is responsible for the large negative shift of However, the onset potential of the catalyst remains unchanged,
the onset potential for O2 reduction by the catalyst when it is placed suggesting that the incorporation of a proton carrier does not change
inside a HBM. Indeed, the slow and steady current rise we observe the thermodynamics of the catalyst in the HBM system, but rather
resembles the O2 reduction profiles of Fe porphyrins appended to enhances the kinetics of proton transport.
SAMs exhibiting slow electron transfer35,36
.
To further interrogate the mechanism of proton transport inside
the HBM, we studied the O2 reduction activity of Cu BTT at 10 ◦C.
At this temperature, DMPC monolayers exist in the gel phase41
Proton carrier incorporation
We next incorporate an alkyl phosphate, mono-N-dodecyl where flip–flop diffusion is suppressed42, but the O2 diffusion
phosphate (MDP), in our HBM system to facilitate proton rate across the lipid layer is similar to that at room temperature
transport to the embedded catalyst and to act as a molecular (Supplementary Note 6). Unlike at 26 ◦C, the O2 reduction current
switch. Proton carriers, such as aliphatic acids and amines, orient of the HBM with one equivalent of MDP at 10 ◦C (Fig. 4, purple
themselves with their polar head groups towards the lipid–water curve) is similar to that of the HBM with DMPC only at 10 ◦C and
interface37. However, in the presence of a driving force such as a pH 26 ◦C (Supplementary Fig. 10, red curve and Fig. 4, red curve). We
gradient, they deliver protons across the membrane via ‘flip–flop’ hypothesize that because MDP cannot undergo flip–flop diffusion
diffusion38,39. Proton shuttling is important in many biological at 10 ◦C, it is not an effective proton carrier and hence does
systems, such as mitochondrial membranes8. We incorporate MDP not enhance the O2 reduction activity of the catalyst. However,
in the HBM as a unique proton carrier because it is diprotic and when the surface is warmed to 26 ◦C after being cooled, MDP is
hence its ability to transport protons can be modulated by changes reactivated as a proton carrier, resulting in revived O2 reduction
in pH, unlike previously used acids and amines. We confirm activity (Supplementary Fig. 10, green curve).
the presence of MDP in the lipid layer of the HBM using mass
The integrity of the lipid layer is examined by blocking
spectrometry (Supplementary Fig. 9). Figure 3 demonstrates that experiments with a solution of K3Fe(CN)6 (Supplementary Fig. 11;
incorporating one equivalent of MDP into the lipid layer of the ref. 43). In the absence of the lipid layer, we observe a combination
HBM inhibits the O2 reduction activity of the Cu complex of BTT of Fe(II)/Fe(III), Cu(I)/Cu(II), and BTT redox couples in the cyclic
further at pH 7 (see green curve). At pH 7, MDP exists as an voltammogram. The current significantly decreases on addition of
equilibrium mixture of RHPO−4 /RPO42− (ref. 40). Protonation of DMPC, suggesting the presence of a well-packed monolayer of lipid
this equilibrium mixture is dominated by the conversion of RPO24− on the SAM (ref. 43). More importantly, the current originating
to RHPO−4 . RHPO−4 is a poor proton carrier, as the transport of from the Fe(II)/Fe(III) couple is similar for both the lipid-only
charged species through the hydrophobic interior of the lipid layer HBM and the HBM with MDP, indicating that the incorporation
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NATURE MATERIALS DOI: 10.1038/NMAT3974
ARTICLES
CMheemthicoalds swere obtained from commercial sources and used without further
100
purification unless otherwise specified. Aqueous solutions were prepared using
Milli-Q water (>18 M cm−1). Potassium phosphate buffers (100 mM, pH 5 or 7)
were sparged with Ar or O2 for 30 min before each experiment.
Electrochemical studies were carried out using a CH Instruments 760 D
Electrochemical Workstation (Austin, TX). For studies in aqueous and ethanolic
solutions a three-electrode cell was used with a Pt wire counter electrode.
Electrochemical potentials are measured and reported with respect to a no-leak
Ag/AgCl/3 M KCl reference electrode. The onset potential of O2 reduction is
defined as the potential at which 5% of the maximum current is reached.
Glassy carbon electrodes were polished with alumina (0.05 µm) and
0
pH 7
pH 5
pH 7
Lipid with MDP
sonicated in water before use. Au working electrodes were deposited using an
electron-beam vacuum deposition apparatus. A Cr adhesion layer (20 nm),
followed by a Au layer (250 nm), was deposited on Pyrex glass slides. The
electrodes were rinsed with water and EtOH before use.
Lipid without MDP
Self-assembled monolayers (SAMs) of the Cu catalysts were attached to the
Au working electrodes in three steps. The thiol group was deprotected to give free
BTT by adding the tritylated thiol (1.0 mg) to neat trifluoroacetic acid (100 µl),
resulting in a yellow solution. Triethylsilane (∼100 µl) was added dropwise until
the solution became colourless. The resulting solution was then diluted with
Ar-sparged EtOH (7.0 ml). The Au electrodes were immersed in the BTT solution
for 2 h and washed with EtOH. The BTT-Au surfaces were immersed in an
ethanolic Cu(ClO4)2 solution (6.7 mM) for 1 h. The electrodes were rinsed three
times with EtOH and three times with pH 7 buffer solution. The Cu complex of
BTT was embedded in a HBM using a previously reported procedure with pure
DMPC or DMPC with one equivalent of mono-N-dodecyl phosphate relative to
DMPC (ref. 20).
Rotating ring-disk electrode experiments were performed using a ring-disk
assembly with an interchangeable disk (E5 series, Pine instruments) connected to
a MSRX rotator (Pine instruments) set to 400 r.p.m. The Au disk electrode was
polished sequentially with 9 µm, 3 µm, 1 µm, 0.25 µm and 0.05 µm diameter
diamond polish (Buehler) and sonicated in water after each stage. The Pt ring
electrode was cleaned electrochemically by cycling from −400 mV to +1700 mV
at 100 mV/s in an aqueous solution of HClO4 (0.1 M) until the current of oxide
stripping at ∼350 mV remained constant. A glassy carbon electrode was used as a
standard for the two-electron reduction of O2, which has been described
previously46. The collection efficiency of the ring electrode, which was held at
+710 mV, was determined to be 15.5%. For all reported data, the ratio of ring
current to disk was obtained at −500 mV.
Figure 5 | Proton switch evaluation. Percentage of maximum current of O2
reduction at −0.5 V by the Cu complex of BTT with lipid (black squares)
and lipid with the MDP switch (red circles).
of MDP does not adversely affect the integrity of the lipid layer. This
suggests that MDP does not phase segregate in DMPC at pH 5 and
7. Acids have been shown to phase segregate only when they are
fully protonated, and MDP exists predominantly as charged species
in our system44,45
.
pH-sensitive switch
The RH2PO4/RHPO−4 /RPO42− equilibrium combined with the
hindered proton transport by RHPO−4 allows MDP to act as
a pH-dependent switch for O2 reduction inside the HBM. To
evaluate the viability of MDP as a reversible switch for proton
transport, we change the pH of the bulk solution in situ while
monitoring the O2 reduction activity of the Cu complex of BTT
using chronoamperometry (Fig. 5 and Supplementary Fig. 12).
The amount of O2 reduction current by the catalyst increases
substantially on changing the solution from pH 7 to pH 5. By
acidifying the solution, the MDP proton carrier switch is turned
on, increasing the flux of rate-limiting proton transfer to the
catalyst, thus increasing the O2 reduction current. The O2 reduction
activity of the catalyst is then shut down by turning off the
MDP switch. Indeed, on readjusting the solution to pH 7, the O2
reduction current decreases to within 5% of its original value at
pH 7, demonstrating that MDP is a reversible switch for proton
transport in a HBM (Fig. 5, red circles). In the absence of MDP,
the lipid layer of the HBM effectively blocks proton transport to
the catalyst. Therefore, the O2 reduction current in the absence of
MDP is not sensitive to changes in the pH of the bulk solution
(Fig. 5, black squares).
Chronoamperometry was performed in O2-saturated pH 7 buffer solutions
(2.6 ml). The pH of the solution was adjusted to 5 in situ with an Ar-sparged
solution of H3PO4 (15 µl). The pH of the solution was adjusted back to 7 with an
Ar-sparged solution of KOH (15 µl). An Ar-sparged solution of pH 7 buffer
(15 µl) was added instead of acid or base in control experiments. Before and after
chronoamperometry, blocking experiments with a solution of K3Fe(CN)6 were
performed to confirm that the integrity of the lipid layer of the HBM is not
compromised. A separate control experiment in which an Ar-sparged solution of
pH 7 buffer (15 µl) was added twice before the addition of an Ar-sparged solution
of H3PO4 (15 µl) further demonstrated that the increase in O2 reduction current
at pH 5 is not due to degradation of the HBM (Supplementary Fig. 12b). To
evaluate the proton switch, differences in the percentage change in current before
and 5 s after addition were calculated. These values were then normalized for the
percentage change in current observed in the control experiments with an added
Ar-sparged solution of pH 7 buffer.
Received 21 September 2013; accepted 28 March 2014;
published online 11 May 2014
Conclusions
We have constructed a system in which a proton transfer switch
is used to turn on and off a molecular catalyst by controlling
proton flux to the catalyst. By changing the pH of the bulk solution,
the ability of MDP to act as a proton carrier inside a HBM can
be controlled reversibly. The rate of proton transfer through the
lipid layer in turn modulates the O2 reduction activity of the
embedded catalyst, which itself is an example of a synthetic Cu
O2 reduction catalyst supported on a Au electrode. The rational
design of the BTT ligand, which is tailored to form a HBM
on Au, exhibits catalytic activity similar to that of synthetic Cu
O2 reduction catalysts supported on carbon. This electrochemical
platform allows the precise and independent control of both the
thermodynamics and kinetics of proton transfer to a molecular
catalyst. This approach can ultimately be used to acquire a unique
mechanistic insight into PCET reactions in biological systems and
energy conversion processes.
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Acknowledgements
C.J.B. acknowledges a National Science Foundation Graduate Research Fellowship
(NSF DGE-1144245) and a Springborn Fellowship. E.C.M.T. acknowledges a Croucher
Foundation Scholarship. We thank Michael Cason for his assistance in preparing Au on
glass substrates. We thank the US Department of Energy (DE-FG02-95ER46260) for
support of this research. This work was carried out in part in the Frederick Seitz
Materials Research Laboratory Central Facilities, which are partially supported by the
US Department of Energy (DE-FG02-07ER46453 and DE-FG02-07ER46471).
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Author contributions
C.J.B., E.C.M.T., S.C.Z., A.H. and A.A.G. designed the experiments. C.J.B., E.C.M.T. and
T.B.S. performed the experiments. Y.L. synthesized BTT. C.J.B., E.C.M.T., Y.L., S.C.Z.,
A.H. and A.A.G. wrote the paper. C.J.B., E.C.M.T., A.H. and A.A.G. analysed the data. All
authors discussed the results and commented on the manuscript.
Additional information
29. Hosseini, A. et al. Ferrocene embedded in an electrode-supported hybrid lipid
bilayer membrane: A model system for electrocatalysis in a biomimetic
environment. Langmuir 26, 17674–17678 (2010).
Supplementary information is available in the online version of the paper. Reprints and
permissions information is available online at www.nature.com/reprints.
Correspondence and requests for materials should be addressed to A.A.G.
30. Rowe, G. K. & Creager, S. E. Interfacial solvation and double-layer effects
on redox reactions in organized assemblies. J. Phys. Chem. 98,
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Competing financial interests
The authors declare no competing financial interests.
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