How to Control the Rate of Heterogeneous Electron Transfer across the Rim of M6L12and M12L24Nanospheres

Article abstract of DOI:10.1021/jacs.0c01869

Catalysis in confined spaces, such as those provided by supramolecular cages, is quickly gaining momentum. It allows for second coordination sphere strategies to control the selectivity and activity of transition metal catalysts, beyond the classical methods like fine-tuning the steric and electronic properties of the coordinating ligands. Only a few electrocatalytic reactions within cages have been reported, and there is no information regarding the electron transfer kinetics and thermodynamics of redox-active species encapsulated into supramolecular assemblies. This contribution revolves around the preparation of M6L12 and larger M12L24 (M = Pd or Pt) nanospheres functionalized with different numbers of redox-active probes encapsulated within their cavity, either in a covalent fashion via different types of linkers (flexible, rigid and conjugated or rigid and nonconjugated) or by supramolecular hydrogen bonding interactions. The redox probes can be addressed by electrochemical electron transfer across the rim of nanospheres, and the thermodynamics and kinetics of this process are described. Our study identifies that the linker type and the number of redox probes within the cage are useful handles to fine-tune the electron transfer rates, paving the way for the encapsulation of electroactive catalysts and electrocatalytic applications of such supramolecular assemblies.

Full text of DOI:10.1021/jacs.0c01869

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Article
How to Control the Rate of Heterogeneous Electron Transfer
Across the Rim of M6L12 and M12L24 Nanospheres
Riccardo Zaffaroni, Eduard O. Bobylev, Raoul Plessius, Jarl Ivar van der Vlugt, and Joost N. H. Reek
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c01869 • Publication Date (Web): 17 Apr 2020
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How to Control the Rate of Heterogeneous Electron Transfer Across
the Rim of M6L12 and M12L24 Nanospheres
Riccardo Zaffaroni,†,§ Eduard.O.Bobylev,†,§ Raoul Plessius,† Jarl Ivar van der Vlugt,† and Joost N.
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H. Reek*,†
† van ’t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, the
Netherlands.
§ Both authors contributed equally to this work.
ABSTRACT: Catalysis in confined spaces, such as provided by supramolecular cages, is quickly gaining momentum. It
allows for second coordination sphere strategies to control the selectivity and activity of transition metal catalysts, beyond
the classical methods like fine-tuning the steric and electronic properties of the coordinating ligands. Only a few
electrocatalytic reactions within cages have been reported, and there is no information regarding the electron transfer
kinetics and thermodynamics of redox-active species encapsulated into supramolecular assemblies. This contribution
revolves around the preparation of M6L12 and larger M12L24 (M= Pd or Pt) nanospheres functionalized with different numbers
of redox-active probes encapsulated within their cavity, either in a covalent fashion via different types of linkers (flexible,
rigid and conjugated or rigid and non-conjugated) or by supramolecular hydrogen bonding interactions. The redox-probes
can be addressed by electrochemical electron transfer across the rim of nanospheres and the thermodynamics and kinetics
of this process are described. Our study identifies that the linker type and the number of redox probes within the cage are
useful handles to fine-tune the electron transfer rates, paving the way for the encapsulation of electro-active catalysts and
electrocatalytic applications of such supramolecular assemblies.
INTRODUCTION
supramolecular cages.25-26 Furthermore, little is known
about the feasibility of heterogeneous electron transfer
from an electrode to a redox-active species encapsulated
by a supramolecular cage. The few reported examples
concern small supramolecular assemblies where the redox
probe is readily accessible or in close proximity to the
electrode surface so that direct electron transfer is
possible.27-29 Similarly, the reported redox-active cages are
supramolecular assemblies where the outer-shell of the
Catalytic transformations are essential for the
preparation of chemicals and materials in a sustainable
manner.1-3 Although homogeneous catalysis is a well-
developed field, many challenges still remain.4 In general,
control over the selectivity, stability and activity of the
catalyst are key parameters to consider.5 The selectivity
and activity of molecular catalysts can be optimized by
fine-tuning the electronic and steric properties of the
ligands coordinated to the metal center. As a result,
catalyst development to date has been dominated by
design and synthesis of sophisticated novel and
increasingly complex ligands. More recently, the field of
cage catalysis has proven its potential to control crucial
catalyst parameters.5-12 Indeed, it has been demonstrated
that molecular catalysts encapsulated in supramolecular
cages display novel selectivity in several reactions,
affording products that are inaccessible by conventional
methods. Other potential positive cage effects include i)
higher stability of encapsulated catalysts vs. species in bulk
solvent and ii) enhanced reaction rates due to local
environment effects and substrate preorganization.13-21
cage is functionalized with redox probes or the building
30-31
blocks themselves are redox-active.27,
In this
contribution we explore the redox-chemistry of
supramolecular M6L12 and M12L24 cages with different
redox-active moieties in their interior. Detailed
electrochemical studies allows the evaluation of the
thermodynamics and kinetics of electron transfer from the
electrode to the electrochemical probes inside the spheres.
We evaluate the effect of the linker between the probe and
the rims of the cage by using: I) a ferrocene (Fc) moiety
covalently attached to a ditopic bis(pyridine) building
block through a flexible linker (Figure 2, FcBB A); II) a
tetrathiafulvalene (TTF) moiety covalently attached to a
planar and fully conjugated bis(pyridine) building block,
resembling the structure of a molecular wire (Figure 2,
TTFBB B); III) a TTF-containing bis(pyridine) building
block featuring a biphenyl moiety with a built-in 90° twist
between two adjacent aromatic rings to break the
conjugation of the structure (Figure 2, twistedTTFBB C)
and IV) using supramolecularly encapsulated ferrocenyl
Cage catalysis is now rapidly developing and many
examples spanning
a
wide variety of catalytic
transformations can be found in literature.6-8 Chief among
these are palladium catalyzed reactions, hydrolysis
reactions, SN2 reactions, rearrangement reactions and
photochemical reactions.14, 21-24 Interestingly, so far, there
are only few reports of catalytic redox reactions in
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Figure 1. Representation of modified M6L12 nanospheres (specifically [Pt6E10B2]12+) with two encapsulated TTF redox probes
undergoing heterogeneous electron transfer at a glassy carbon electrode. On the left TTF in its reduced form; on the right in
its oxidized form. The cage frame is optimized at molecular mechanics level (MMFF) and shown in wire-style; carbon in white,
nitrogen in blue and metallic corners as grey spheres.
sulfonate redox probes that are encapsulated via hydrogen
bonding interactions to guanidinium functionalities20
present in the interior of a supramolecular cage (Figure 2,
D). Furthermore, as shown in Figure 3, the redox-probe
concentration in the cage interior is modulated by using a
mixture of unfunctionalized building block BBH E and
redox probe-functionalized derivatives, i.e. FcBB A or
TTFBB B. We show that the rates of electron transfer are
highly dependent on the type of linker used. Flexible and
non-conjugated linkers significantly decrease the rates of
heterogeneous electron transfer to quasi-reversible
Nernstian regimes while the fully conjugated linker
negligibly affects the electron transfer. Furthermore the
rates of electron transfer are also dependent on the
number of redox probes encapsulated within the
nanosphere; the rates exponentially decrease when the
number of redox species present in the nanosphere
increases. On the other hand, thermodynamics of electron
transfer are not affected by redox probe encapsulation.
This study is relevant to the development of catalyst-
functionalized cages for electrocatalytic transformations
so that the heterogeneous electron transfer rates can be
matched with the rate at which the catalyst operates in
order to avoid i) accumulation of reducing/oxidizing
equivalents that could potentially be harmful to the
catalyst and ii) lack of reducing/oxidizing equivalents that
can compromise the stability of reactive intermediates.
RESULTS AND DISCUSSION
Strategy
With electrocatalysis as future application in mind, we set
out to investigate the electrochemical behavior of redox-
active centers encapsulated inside M6L12 and M12L24 Fujita-
type nanospheres,32-34 as depicted in Figure 1. These
supramolecular assemblies, based on ditopic bis(pyridine)
building blocks held together by tetra-coordinated square
planar palladium or platinum corners, are interesting
because their relatively large size (about 3 nm diameter for
M6L12 and 5 nm diameter for M12L24) can be exploited to
simultaneously accommodate several redox probes. This
allows for the independent study of different variables: i)
the number of ‘guests’ can be easily tuned by changing the
ratio of functionalized vs. unfunctionalized building blocks
prior to cage self-assembly; ii) the ease of functionalization
of the standard ditopic bis(pyridine) building block
enables synthetic strategies to introduce a diverse range of
linkers between the redox probe and the rim of the cage,
which may affect the electron transfer process; iii) different
redox probes can be encapsulated within the nanospheres
to study electron transfer processes that are key for
Figure 2. Overview of the building blocks prepared A, B and C and supramolecular encapsulation of redox probes via hydrogen
bonding between sulfonate groups and guanidinium functionalized cage.
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electrocatalysts. Furthermore, the nanosphere size can be As the environment in the cage cavity differs from the
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precisely controlled by the choice of metal corners;
palladium ions preferentially afford larger M12L24
nanospheres while platinum precursors result in formation
of M6L12 cages.35
bulk solution, kinetics and thermodynamics of electron
transfer of encapsulated redox probes are expected to differ
relative to their respective free diffusing species. In
particular, the type of linker employed to connect the
redox probe to the cage framework can have significant
impact on the kinetics of electron transfer. Thus, linear and
conjugated linkers resembling molecular wires with large
frontier orbital overlap are expected to have less influence
on the electron transfer rates compared to flexible or non-
conjugated ones. The number of encapsulated redox
probes is also expected to be a key parameter, as the
proximity of different probes might induce electrostatic
interactions, which can affect both the redox potentials of
the individual units but also the electron transfer rates.
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Synthesis and characterization of the supramolecular
cages functionalized with redox-probes
Detailed information regarding the synthesis of the
respective building blocks and their analytical
13
characterization (1H, C and DOSY NMR spectroscopy as
well as high resolution mass spectrometry) can be found in
the SI. Single crystals of building blocks A, B and C,
suitable for X-ray diffraction, were grown either by layering
a CH2Cl2 solution of the building blocks with hexanes or by
slow evaporation of solvents. The molecular structure for
FcBB A confirms the presence of the flexible non-
conjugated amide-derived linker that covalently connects
the ferrocene unit to the bis(pyridine) backbone. The TTF-
containing building blocks B and C display more rigidity
along the entire molecular structure. For TTFBB B the
torsion between the central phenyl ring of the backbone
and the TTF moiety is only 2.9°, with TTF in the usual boat
conformation with 158° torsion between its two 5-
membered rings. The twisted building block TTFBB C
shows similar angles but the most important feature is the
89.5° torsion between the two adjacent phenyl rings along
the linker structure.
The supramolecular M12L24 assemblies were prepared
according to literature procedures,20 by mixing a PdII metal
precursor (with weakly coordinating anions, typically
tetrafluoroborate or hexafluorophosphate-salts) with two
Figure 3. Overview of cage self-assembly stoichiometry and Spartan model of the resulting cage (Pt6E10B2)12+ optimized at molecular
mechanics level (MMFF). The cage frame is shown in wire-style, platinum corner as gray spheres and TTF moieties in yellow and
white style.
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equivalents of bis-pyridine building block. After addition
of a suitable solvent (in general MeCN-d3 or mixtures of
MeCN-d3 and DCM-d2, for solubility reasons) the solutions
were stirred overnight in a closed Schlenk flask at 60 °C.
The characterization methods available to confirm the
formation of the assemblies are showcased for the
palladium nano-cage containing 24 FcBBs A, [Pd12A24]24+
(Figure 4). Data for all assemblies are compiled in the SI.
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The formation of the desired assembly is firstly
supported by 1H NMR spectroscopy. Upon pyridine
coordination to the metal corners, the ortho-pyridine
protons undergo deshielding, which results in a low-field
shift of such protons of approximately 0.4 ppm (Figure 4).
The symmetry and broadening of the 1H NMR spectrum is
also an indication for the formation of highly symmetric,
large assemblies.36 Secondly, a DOSY NMR spectrum of the
reaction solution features a single species with a logD value
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of -9.6 m2s-1, in agreement with previously reported data on
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similar nanospheres.20,
In contrast, under the same
experimental conditions, the free building block, being
considerably smaller than the supramolecular cage
assembly, shows a logD value of -8.9 m2s-1. Cryospray-
ionization MS (CSI-MS) mass spectrometry confirms the
formation of
a
species with overall [Pd12A24]24+
composition. The spectrum shows several signals
belonging to the desired species, in particular species of
the type [(Pd12A24)](24-n)+(BF4)n with different numbers of
anions. The measured signals and their isotopic patterns
are in agreement with the simulated spectra that are
compiled in the SI (Figure 4 and Figure S12 to Figure S21).
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Figure 4. A) Representation of [Pt6A12]12+ nanosphere (right) and [Pd12A24]24+ nanosphere (left). The cage structures are optimized
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at molecular mechanics level (MMFF) and shown in wire-style; carbon in white, nitrogen in blue, oxygen in red, metallic corners
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as grey spheres (right is Pt, left is Pd) and Fe ions as orange spheres. B) H-DOSY-NMR overlay for FcBB A (red), [Pt6A12]12+
nanosphere (blue) and [Pd12A24]24+ nanosphere (violet) in a 1:1 mixture of CD2Cl2 and CD3CN at 25 °C. C) Obtained (red) and
calculated (black) CSI-MS for the 14+ species [(Pd12A24)(BF4)14]14+. D) Obtained (red) and calculated (black) CSI-MS for the 7+
species [(Pt6A12)(PF6)7]7+. E) 1H-NMR of FCBB A (red), [Pd12A24]24+ (violet) and [Pt6A12]12+ (blue).
Similarly, performing the same self-assembly process
using a PtII precursor affords smaller Pt6A12 cages after
stirring the reaction mixture at 85 °C for 2 days (Figure 4
and Figure S34 to Figure S40). Because the length of the
TTF functionalized building blocks is about 1.5 nm for
TTFBB B and about 2.0 nm for twistedTTFBB C, and given
their rigid nature, it is unlikely that 12 of those building
blocks self-assemble into M6L12 spheres as a result of the
significant steric hindrance induced in the cage interior.
This is supported by rudimentary molecular mechanics
calculations (Spartan). Therefore nanospheres containing
the redox-active TTF building blocks were prepared by
using mixtures of TTF building blocks and
unfunctionalized building block BBH E to generate cage
assemblies of the type M6ExL12-x (L = TTFBB B or
twistedTTFBB C). When cage self-assembly is performed
Figure 5. Left: cyclic voltammograms at different scan rates for [Pd12A24]24+ in a 1:1 mixture of MeCN and DCM. Right: cyclic
voltammogram and differential pulse voltammetric (DPV) measurement for [Pt6E10B2]12+ in MeCN, showing both the first and
second oxidation waves of the TTF probe.
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with two different building blocks LI and LII, the resulting
solution contains a mixture of cages of the type MyLIxLII
ferrocenyl sulfonate can be added to the cage solution,
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while the addition of an excess leads to formation of a
precipitate. The latter is assumed to be a guanidinium cage
with 24 ferrocenyl sulfonate moieties in the interior and
ferrocenyl counter ions at the outside. If more solvent is
added to the NMR sample, the precipitate remains, but
addition of more guanidinium cage leads to dissolution of
2y-x
(y=6,12), containing different amounts of building block LII,
specifically the amount of LII follows
a
Gaussian
distribution centered around the value 2y-x. Thus, when
mixed building block cages are mentioned, those are
always to be intended as mixtures of different species as
opposed to specific single composite species. For small
Pt6L12 cages with sterical demanding building blocks such
as TTFBB B or twistedTTFBB C, rudimentary molecular
modeling shows that the cavity of such cages is congested
when more than three TTF containing building blocks are
present (Figure S162). CSI MS data confirms that for
1
the precipitate and the resulting H NMR spectrum is
identical to the one of a guanidinium cage with
encapsulated ferrocenyl sulfonates. The encapsulation of
the ferrocene derivative is also confirmed by DOSY NMR
spectroscopy (Figure S82). A diffusing species containing
all the signals belonging to the cage and those of the
ferrocene moiety is present at logD value of -9.35. A second
diffusing species with lower diffusion coefficient is present
and identified as the tetrabutylammonium counter ions
that are released after binding the ferrocenyl sulfonates to
the guanidinium. CSI-MS data were recorded for solutions
of [(Pd12D24)](OTf)24 with different amounts (3,8 and 16
equivalents) of [FcSO3]- guest, showing in all cases the
expected signals for host-guest complexes, in agreement
with the isotopic patterns (Figure S83 to Figure S107).
Several attempts to grow single crystals of cage samples
suitable for X-ray diffraction were undertaken specifically
by vapor diffusion and solvents layering (several solvents
combinations) at room temperature, at +5 °C and at -20 °C.
Unfortunately all the attempts were unsuccessful.
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(Pt6EnB12-n)
12+ these cages formed predominantly with n=0,1
and 2 with the ratio of different composites changing
according to the stoichiometry chosen, and in negligible
amounts n=3 (Figure S51 to Figure S61 and Figure S64 to
Figure S71); species with four or higher TTF containing
building blocks were not observed by CSI-MS
measurements. Exact quantification of single composites is
unfortunately not possible due to differences in
ionizability of the different species under MS conditions.
Formation of larger M12L24 Pd-cages containing TTF redox
moieties was unsuccessful as mixing the TTF building
blocks with the palladium precursor in an attempt to form
large Pd12L24 cages resulted in palladium black formation
within minutes.
The formation and characterization of a guanidinium
functionalized supramolecular cage, [(Pd12D24)](OTf)24,
was carried out as described previously.20 Encapsulation of
ferrocenyl sulfonate guests via hydrogen bonding was
Electrochemistry of covalently encapsulated redox
probes
Cyclic voltammograms of nanospheres containing redox
1
confirmed by H NMR titration studies. The shifts of all
moieties clearly show
a
single reversible wave,
relevant peaks are consistent with the ferrocene unit being
encapsulated (Figure S81). About 24 equivalents of
corresponding to the oxidation of the redox probes, as
Table 1. Summary of the E1/2 redox potentials and calculated k0 of heterogeneous electron transfer for the redox-active building
blocks A, B and C and their respective cages (with different amounts of redox-probe present). Data for FcBB A and FcBB A
containing cages were recorded in a 1:1 mixture of MeCN and DCM while data for TTF containing building blocks and their cages
were collected in MeCN.
nd
Sample
Number of
redox
probes
E11/2 1st
ko
E2
2
ko
2
1
1/2
oxidation (V
(cm s-1)
oxidation (V
(cm s-1)
vs. Fc/Fc+)
vs. Fc/Fc+)
FcBB, A
[Pt6A12]12+
-
12
1
0.262
0.215
0.211
4.569·10-2
9.94·10-3
2.90·10-3
6.98·10-3
6.1·10-4
-
-
-
-
-
-
-
-
-
-
[Pt6E11A1]12+
[Pd12E23A]24+
[Pd12A24]24+
1
0.281
0.314
24
-
1
5.382·10-2
3.780·10-2
1.442·10-2
1.237·10-2
6.51·10-4
3.09·10-4
TTFBB, B
[Pt6E11B]12+
[Pt6E10B2]12+
0.029
0.022
0.489
0.448
2
0.036
0.448
-
1
7.046·10-2
4.64·10-3
2.147·10-2
1.09·10-3
TwistedTTFBB, C
[Pt6E11C]12+
-0.037
-0.021
0.340
0.343
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illustrated for the [Pd12A24]24+ cage in Figure 5 (left). For the
configuration with 6π electrons in each TTF system;
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TTF-containing cages, a second quasi-reversible wave is
present at more anodic potential, corresponding to the
second oxidation of the TTF moiety. Figure 5 (right) shows
a typical example of such a voltammetric plot.
formation or breaking of this aromatic stable configuration
leads to molecular reorganization, and this required
movement of the atoms upon this redox event translates
into a slower heterogeneous electron transfer rate.
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Comparison of the dataset obtained for the cage samples
with the dataset obtained for their respective free diffusing
redox active building blocks reveals a small shift of the
half-wave potential (typically in the order of ±10-50 mV)
upon encapsulation of the redox-active probes, which
suggests that oxidation of the redox probes is only slightly
different (±0.2-1.2 kcal mol-1). Table 1 summarizes the
values of the half-wave potentials measured for the
different cages and building blocks.
Linker Influence
To compare the different type of linkers employed, this
section will focus on assemblies with two different building
blocks containing on average only one redox probe per
cage; specifically [Pt6E11A]12+, containing the flexible
ferrocene functionalized building block A, [Pt6E11B]12+
containing the linear TTF building block B and [Pt6E11C]12+
containing the twisted version of the TTF building block
where conjugation is broken. When the redox probe is
encapsulated with a flexible and non-conjugated linker
such as for cage [Pt6E11A]12+, approximately a 16-fold
decrease in electron transfer rate constant is observed. The
electron transfer is slowed by more than one order of
magnitude compared to the electron transfer rate of the
free building block. Electron transfer is however attributed
to the intrinsic linker flexibility, which allows the redox
probe to bend toward the large cage windows so that direct
electron transfer from the electrode surface can still occur.
For cages containing one TTF moiety, the rigidity of the
linkers prevents bending of the unit toward the cage
windows and therefore electron transfer is unlikely to
happen by close contact of the electrode surface and the
probe. For the cage containing TTFBB B, the rate of
electron transfer for the free building block compared to
the encapsulated analog differs only slightly, staying
within the Nerstian reversible regime. The reason for the
overall fast electron transfer is attributed to the fully
conjugated linker, resembling the structure of a molecular
wire, facilitating the electron transfer step. Importantly,
this indicates that the cage framework itself not only has
negligible influence on thermodynamics but also on the
electron transfer kinetics.
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Analysis of peak current vs. square root of the scan rate
plots provides further details on the electrochemical
process. In all cases, both for the assembled cages
containing redox-probes and for the stand-alone redox-
active building blocks, the plots show a linear trend over a
broad scan speed range, indicating Nernstian behavior
(Figure S112). The linear trend is also an indication that the
analytes under investigation are in solution and do not
adsorb to the electrode surface during the electrochemical
measurement nor do they react with the working
electrode.38-39 As shown in Figure S119 and Figure S132,
stability of cages upon electrochemical events is also
supported by the overlap of consecutive voltammetric
traces. For the cage samples, the slopes of the lines are
smaller than for their respective building blocks, in
agreement with their difference in size. From these slopes,
using the Randles–Sevcik equation,39 diffusion coefficients
can be calculated, which agree, within experimental error,
to diffusion coefficients obtained from DOSY NMR
spectroscopy.
Heterogeneous electron transfer rate constants k0 were
calculated by the method originally proposed by Nicholson
in 1965 and revised by Paul and Leddy in 1995.40-41 This
method is based on peak potential separation; it relates k0
to the parameter , which can be calculated from the
parametric equation proposed by Paul and Leddy.40-42
Because this method relies on the peak potential
separation, for it to be reliable, it is important that any
residual solution resistance is properly compensated for.
The calculated k0 values for the cages under investigation
and for the free diffusing building blocks are compiled in
Table 1.
For the cage containing building block C, the rate of
electron transfer is slowed about 15 times compared to its
free building block. The TTF moiety is encapsulated within
the interior of the cage, but it also has a 90° twist along the
rigid linker structure, which effectively breaks conjugation,
as indicated by DFT orbital computations (Figure S163 to
Figure S167). The absence of frontier orbital overlap
prohibits fast electronic communication between the TTF
moiety and the rest of the structure, leading to overall
slower kinetics.
The calculated rates of heterogeneous electron transfer
k0 for the free building blocks are well within the Nernstian
reversible regime displaying fast electron transfer kinetics.
Oxidation of the twisted TTF building block C proceeds
with a k0 of 7.04·10-2 cm s-1 that is close to the one reported
for free TTF.43 The TTF moiety of building block B displays
a slower rate of heterogeneous electron transfer (5.382·10-2
cm s-1), suggesting that the TTF moiety is part of a larger -
system (vide infra). For both TTF containing building
blocks B and C, the second electron transfer rate constant
k02 is lower than the first one, consistent with the fact that
the doubly oxidized TTF units possess an aromatic
Influence of the number of redox probes
The heterogeneous electron transfer rates are different
when more than one redox probe is encapsulated within
the cavity of the nanosphere. In fact, for [Pt6A12]12+
containing 12 Fc redox probes the electron transfer rate is
about 4 times slower than for its free diffusing building
block. The presence of 12 redox probes within the interior
of the nanosphere was expected to more drastically affect
the rates of electron transfer, however, as the cavity of this
particular nanosphere is sterically crowded (see modeling
structures Figure 4 right) and the linker flexibility allows
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the ferrocene units to bend towards the cage rim, fast ferrocenyl or TTF dendrimers and polymers, both in
solution or immobilized on electrode surfaces.44-46
Important for this behavior is the fast molecular tumbling
rate of the cage in solution. The tumbling rate can be
roughly estimated through Newtonian motion laws of
spherical objects. For a spherical object of about 5 nm in
diameter, the tumbling rate in acetonitrile is roughly 2·108
s-1 at room temperature.47 As the tumbling rate of the cage
in solution is considerably faster than the timescale of the
voltammetric experiment, all redox-active probes within
the molecular cage are identical, even at very fast scan
rates, and on average equally distant from the electrode
surface.48 Still, this phenomenon alone is not sufficient to
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direct electron transfer from the electrode is facilitated by
such conformations. The larger nanospheres of the type
M12L24 provide a large cavity with less steric repulsion and
as such the redox probes reside on average more in the
center of the structure, away from the cage windows
(Figure 4 left). When only one Fc redox moiety is
encapsulated within the cavity of the larger nanosphere
(i.e. [Pd12E23A]24+), the rate of electron transfer is about 6.5
times slower compared to the free diffusing building block
and about 1.5 times slower compared to the crowded
[Pt6A12]12+. This indeed suggests that for the small [Pt6A12]12+
nanosphere the ferrocene units are on average in closer
proximity to the electrode. Interestingly, the cage
[Pd12A24]24+ containing 24 ferrocene units shows a rate of
heterogeneous electron transfer k0 of 6.10·10-4 cm·s-1 that is
about 75-fold slower than for the free diffusing building
block and one order of magnitude slower than the
previously discussed [Pd12E23A]24+ containing only one
redox probe. As such, this trend indicates that the number
of redox active moieties within the cage framework also
has a strong impact on the overall electron transfer rate.
Interestingly, as shown in Figure 5, voltammograms of
cages containing more than one redox-active fragment
feature a single oxidation wave. Although these oxidation
waves are broader than those of the freely diffusing
building block, the single oxidation wave indicates that the
thermodynamics of electron transfer do not change
significantly even when the interior of the cage contains 24
redox probes.
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explain the single-wave behavior for
a
given
electrochemical event. Electrostatic repulsion of the newly
generated charges in the interior of the cage also does not
seem to influence the redox potential of other nearby units.
The solution for the electrochemical experiment always
contains large amounts of a salt such as TBAPF6 (tetrabutyl
ammonium
hexafluorophosphate)
as
supporting
electrolyte. Charges generated in the interior of the cage
upon oxidation of the redox probes are balanced by
diffusion of electrolyte, thereby keeping the net charge
inside the cavity of the cage constant.49 Without
accumulation of charges in the interior of the cage,
electrostatic repulsion is minimized and the
thermodynamics of electron transfer do not change
drastically while the kinetics can be slowed to the limit of
reversibility due to slow ion rearrangement.
This set of experiments shows that the nature of the
linker connecting the redox probe to the backbone of the
building block plays a crucial role for the feasibility of the
electron transfer and it determines its kinetics. As a result,
it is possible to vary the kinetics of electron transfer from
the electrode surface to a redox moiety encapsulated
within the interior of a supramolecular cage whilst keeping
the thermodynamics unaltered. The three building blocks
discussed show fast electrode kinetics when studied as free
The redox-active moieties are encapsulated within the
volume defined by the 5 nm diameter-sized M12L24 cage and
thus are in proximity to one another. This could in
principle lead to electronic and electrostatic
communication between individual redox-sites. However,
as suggested by the single oxidative event observed by
cyclic voltammetry, the redox-probes are sufficiently
isolated from each other to be electrochemically
Figure 7. Room temperature EPR signal of mono-oxidized TTFBB
B (red) and its cage (Pt6E10B2)14+ (black), after bulk electrolysis at
0.35 V vs. Fc/Fc+ in MeCN.
Figure 6. Plot of current measured during electrolysis at constant
potential (0.35 V vs. Fc/Fc+) of cage solution (Pt6E10B2)12+ in
MeCN (black) and its integral (red), informative on the number
of electrons transferred during the electrolysis.
manipulated. This behavior is often seen in literature for
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species in solution. The electrode kinetics of cages the free TTFBB B, i.e. the expected quartet pattern of a
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containing building block A or C are slowed to the limit of
reversibility. This is not a general cage effect, as shown by
the supramolecular assembly containing building block B,
where the electron transfer kinetics are marginally affected
and the redox events stay within the Nernstian reversible
regime.
mono-substituted TTF with coupling to three hydrogen
atoms. By contrast, room temperature EPR spectrum for
the caged TTF radical cations shows a broad signal at the
same g value. Broadening of EPR signals is common and
typically ascribed to zero-field splitting, which may in this
case result from radical-radical interactions in the cage
interior.50-51 EPR simulations for both the free as well as the
encapsulated TTF cation were simulated using an AB2-
pattern with three S = ½ nuclei, in agreement with a mono-
substituted TTF moiety. Comparing the line width of the
two TTF cations, a significant increase of 52% is observed
for the encapsulated system (Figure S168 and Figure S169).
Furthermore, within the cage cavity, the TTF cation has a
decreased contribution of the ‘A’-nucleus to the hyperfine
Radical-radical interactions in the cage interior
9
The formation of radical species after electrochemical
events was further monitored by EPR spectroscopy. Cage
solutions containing on average one and two equivalents
of redox moiety of the type (Pt6E12-nBn)12+ (n=1,2), were
subjected to bulk electrolysis at constant potential at 0.35
V vs. Fc/Fc+. As mentioned earlier, such cages are a mixture
of different species rather than single composite solutions.
CSI-MS data shows that species present in solution are
(Pt6E12)12+, (Pt6E11B)12+, (Pt6E10B2)12+ and to a lesser extent
(Pt6E9B3)12+ with their ratio changing according to the
stoichiometry chosen. Importantly the ratio of the
different composites changes not only according to
Gaussian distribution but also according to steric
congestions. Simultaneous presence of more than three
TTF units in one cage is unlikely due to steric constrains
within the cavity of the small Pt6L12 cages (Figure S162).
Although it is not possible to exclude the formation of
species with larger TTF number based on CSI-MS data, we
can at least conclude that if these species exist, they are
present in low concentrations only. Importantly, the
different composites present in solution have different
ionizability under CSI-MS conditions thus accurate
quantification of mixture composition difficult to obtain.
The plot of the current measured in time is shown in Figure
6 together with its integration plot, which provides
information about the average number of electrons
transferred per cage. The analysis confirms that each TTF
unit in the sample is oxidized by one electron, generating
encapsulated TTF cation radicals (TTF+) that can be
detected by EPR spectroscopy. Figure 7 shows the typical
room temperature EPR spectrum of the radical cation of
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pattern (AA = 2.2455 MHz) compared to the free TTFBB
iso
cation (AAiso = 3.598 MHz).
To gain insights into the nature of such interactions, the
TTF/TTF+ redox-couple was monitored by UV-vis for free
TTFBB B and for cages containing on average 1 or 2
equivalents of TTFBB B, respectively (Figure 8). From
literature, it is known that one-electron oxidation of TTF
generates very stable and deeply colored radical cationic
species that can form (TTF+)2 dimers or, depending on the
conditions (e.g. inducing proximity effects), mixed valence
dimeric (TTF)(TTF)+ species.52-61 The latter have an
absorption maximum around 900 nm in the UV-vis-NIR
spectrum as well as a broad absorption at approx. 2000 nm,
whereas the radical dimer, (TTF+)2, displays absorption
around 800 nm.52-61 For the free TTF building block B only
a band at 650 nm was observed, indicating that neither
radical dimerization nor mixed valence species are formed.
For the cage solution containing on average 2 equivalents
of TTFBB B, a five-fold increase in absorption at 800 nm is
observed compared with free (TTFBB B)+ or cage
(Pt6E11B)13+ containing only one equivalent of TTFBB B (.
This is consistent with radical dimer absorption (TTF+)2.
Typically, the extinction coefficient for the charge transfer
band around 800 nm is higher than the one for the
absorption around 650 nm of TTF+. Assuming that this is
Figure 8. UV-vis spectra of free (TTFBB B)+, cage
(Pt6E11B)13+ and (Pt6E10B2)14+ after bulk electrolysis at 0.35
V vs Fc/Fc+ in MeCN.
Figure 9. Cyclic voltammogram of free tetrabutylammonium
ferrocenyl sulfonate (red) and titration of different equivalents
of this compound into a guanidinium functionalized cage
(Pd12D24)48+ in MeCN showing increasing peak current while E1/2
remains constant.
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precipitation of the cage from solution. After about 50
equivalents of ferrocenyl sulfonate, a new reversible wave
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4
appears that is shifted cathodically by about 150 mV (E1/2
=
0.05 V vs. Fc/Fc+). This last wave is identical to an authentic
sample of free ferrocenyl sulfonate.
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At first glance, the electron transfer process appears to
be more energetically demanding, as suggested by the
large potential shift of approximately 150 mV (~3.5 kcal
mol-1) measured between free and encapsulated ferrocenyl
sulfonate. However, this shift in potential is ascribed to the
multifold interaction between the sulfonate and
guanidinium groups. The hydrogen bonding between the
two complementary functional groups (guanidinium and
sulfonate) is expected to effectively reduce the electron
density at the ferrocene moiety, therefore rendering its
oxidation more difficult. To support this, a new titration
was carried out, monitoring for peak potential shifts of
ferrocenyl sulfonate upon addition of increasing amounts
of n-butylguanidinium hexafluorophosphate. Indeed,
progressively anodic shifting of the redox-event is observed
with an increasing concentration of guanidinium species
(Figure S156 and Figure S157). Interestingly, about 25-30
equivalents of guanidinium salt are necessary to reproduce
a similar potential shift as observed when the ferrocenyl
sulfonate is encapsulated by the guanidinium cage,
reflecting the stronger binding within the sphere due to
the ditopic binding mode. Importantly, the shift can be
entirely attributed to hydrogen bonding.
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Figure 10. Trend of heterogeneous electron transfer rate ko for
increasing amounts of tetrabutylammonium ferrocenyl
sulfonate encapsulated within the cavity of a guanidinium
functionalized cage (Pd12D24)48+
.
true also for the system under investigation, it implies that
the extent of radical dimerization is a minor effect; most
radicals within the cage probably exist as isolated TTF+.
Data for the cage solution (Pt6E11B)12+ containing on
average one equivalent of TTFBB B show a similar behavior
as the free building block as seen in Figure 8.
Overall, the combined data support retention of the
supramolecular cage assemblies upon electrochemical
reactions involving redox-probes in their interior. Despite
most radicals within the cage probably exist as isolated
The data are consistent with the ferrocene derivative
remaining encapsulated throughout the electrochemical
experiment. Firstly, the ferrocenyl peak potential is
constant during the entire titration experiment, which is in
line with strong binding of sulfonates inside the cage, as
previously reported (cage binding affinity to sulfonates ≈
2.1·105 M–1).20 Secondly, the shape of the voltammogram
remains symmetric, which indicates that the ferrocene
undergoes both electrochemical events (oxidation and
back-reduction) at the inside of the nanosphere. In fact, if
the ferrocenyl sulfonate would leave the cage after the
oxidation event and be back-reduced outside the cage, the
shape of the voltammogram would be asymmetric with a
peak potential separation ΔEp of approximately 300 mV
instead of the 70 mV experimentally observed.
TTF+,
the
combination
of
EPR
and
spectroelectrochemistry measurements reveals the
presence of some interactions between the radicals within
the nanosphere to form to a lesser extent (TTF+)2 radical
dimer species.
Electrochemistry of supramolecularly encapsulated
redox probes
Next the electrochemistry of redox probes that were
supramolecularly encapsulated within nanospheres via
hydrogen bonding was evaluated. To probe the
encapsulation of ferrocenyl sulfonate by guanidinium cage,
a titration of ferrocenyl sulfonate into a solution of
guanidinium cage was carried out whilst monitoring the
voltammetric response after every addition of redox probe.
The guanidinium cage itself does not show any
electrochemical anodic response in the potential window
of interest. When ferrocenyl sulfonate is added to this
solution, a reversible wave appears (E1/2 = 0.20 V vs. Fc/Fc+,
ΔEp = 70 mV). Figure 9 shows that increasing amounts of
ferrocenyl sulfonate result in higher peak currents but no
significant potential shift is observed. When about 22
equivalents of ferrocenyl sulfonate are added, some
precipitate forms, in line with the NMR titration described
earlier. From this point, the peak current measured
decreases with increasing amounts of ferrocenyl sulfonate,
indicating that the ferrocenyl sulfonate induces
The ferrocenyl sulfonate displays fast kinetics of electron
transfer (k0 4.25·10-2 cm s-1), similar to reported ferrocene
derivatives and to the ferrocene containing building block
A.62-65 However, when this redox probe is encapsulated
within the cavity of the guanidinium functionalized
nanosphere (1 eq), the rate of electron transfer is about 20
times lower compared to the freely diffusing species.
Furthermore, increasing numbers of redox-active guests
result in an exponential decrease of the heterogeneous
electron transfer rate, similarly as observed for the
covalently encapsulated redox probes (Figure 10). For the
supramolecularly anchored system the rate of electron
transfer becomes about 250 times slower when 22
ferrocenyl sulfonates reside in the nanosphere. The
thermodynamics of electron transfer are again only slightly
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1.
Johansson-Seechurn, C. C. C.; Kitching, M. O.;
affected, as indicated by the constant E1/2 of the
encapsulated ferrocenyl species.
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Colacot, T. J.; Snieckus, V., Palladium-Catalyzed Cross-
Coupling: A Historical Contextual Perspective to the 2010
Nobel Prize. Angew. Chem. Int. Ed. 2012, 51 (21), 5062-5085.
The drastic drop in electron transfer rate also confirms
that the ferrocenyl probes stay encapsulated during the
entire course of the voltammetric measurement; the
guanidinium groups hold the redox probes in place by
2.
Noyori, R., Synthesizing our future. Nat. Chem.
2009, 1 (1), 5-6.
3.
Franke, R.; Selent, D.; Börner, A., Applied
strong
cooperative
binding,
ensuring
effective
Hydroformylation. Chem. Rev. 2012, 112 (11), 5675-5732.
encapsulation and insulation from the bulk solution and
from the electrode, resulting in kinetics of electron transfer
that are in the quasi-reversible Nernstian regime.
4.
Cornils, B.; Herrmann, W. A., Concepts in
homogeneous catalysis: the industrial view. J. Catal. 2003, 216
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(1–2), 23-31.
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Brown, C. J.; Toste, F. D.; Bergman, R. G.; Raymond,
K. N., Supramolecular Catalysis in Metal–Ligand Cluster
Hosts. Chem. Rev. 2015, 115 (9), 3012-3035.
CONCLUSIONS
In this work we have demonstrated the feasibility of the
electron transfer of redox-active species encapsulated in
M6L12 and M12L24 supramolecular assemblies. The linker
connecting the redox probe to the cage building block is a
useful handle to tune the rate of electron transfer.
Envisioning that an (electroactive) catalyst can be
encapsulated into a supramolecular assembly, the nature
of the linker employed as well as the number of redox
species present within the nano-sphere could potentially
be exploited to fine-tune and match the electron transfer
rate to the rate at which the catalyst operates. This strategy
could be advantageous in order to avoid accumulation of
reducing/oxidizing equivalents which could potentially be
harmful to the catalyst.
6.
Vriezema, D. M.; Comellas Aragonès, M.; Elemans, J.
A. A. W.; Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M.,
Self-Assembled Nanoreactors. Chem. Rev. 2005, 105 (4), 1445-
1490.
7.
Leenders, S. H. A. M.; Gramage-Doria, R.; de Bruin,
B.; Reek, J. N. H., Transition metal catalysis in confined spaces.
Chem. Soc. Rev. 2015, 44 (2), 433-448.
8.
Mouarrawis, V.; Plessius, R.; van der Vlugt, J. I.; Reek,
J. N. H., Confinement Effects in Catalysis Using Well-Defined
Materials and Cages. Frontiers in Chemistry 2018, 6 (623).
9.
Pablo, B., Effects of Nanoconfinement on Catalysis.
Edited by Rinaldo Poli. Angew. Chem. Int. Ed. 2017, 56 (27),
7713-7714.
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Yoshizawa, M.; Klosterman, J. K.; Fujita, M.,
Functional Molecular Flasks: New Properties and Reactions
within Discrete, Self-Assembled Hosts. Angew. Chem. Int. Ed.
2009, 48 (19), 3418-3438.
ASSOCIATED CONTENT
11.
Wiester, M. J.; Ulmann, P. A.; Mirkin, C. A., Enzyme
Experimental details on synthesis and characterization
(1H/31P/13C-NMR, MS, XRD), all raw data pertaining to
electrochemistry. This material is available free of charge via
the Internet at http://pubs.acs.org.
Mimics Based Upon Supramolecular Coordination Chemistry.
Angew. Chem. Int. Ed. 2011, 50 (1), 114-137.
12.
Raynal, M.; Ballester, P.; Vidal-Ferran, A.; van
Leeuwen, P. W. N. M., Supramolecular catalysis. Part 1: non-
covalent interactions as a tool for building and modifying
homogeneous catalysts. Chem. Soc. Rev. 2014, 43 (5), 1660-
1733.
AUTHOR INFORMATION
Corresponding Author
* j.n.h.reek@uva.nl
13.
Pluth, M. D.; Bergman, R. G.; Raymond, K. N., Acid
Catalysis in Basic Solution: A Supramolecular Host Promotes
Orthoformate Hydrolysis. Science 2007, 316 (5821), 85-88.
14.
Pluth, M. D.; Bergman, R. G.; Raymond, K. N.,
Acknowledgments
Supramolecular Catalysis of Orthoformate Hydrolysis in Basic
Solution: An Enzyme-Like Mechanism. J. Am. Chem. Soc.
2008, 130 (34), 11423-11429.
Maximilian Dürr,‡ Nicole Orth‡ and Ivana Ivanović-
Burmazović‡ are acknowledged for collection of preliminary
CSI-MS data on cages of the type (Pd12A24)(24-n)+(BF4)n. Dr.
Wojciech Dzik is thanked for work on one of the X-ray
structure determinations.
15.
Horiuchi, S.; Murase, T.; Fujita, M., Diels–Alder
Reactions of Inert Aromatic Compounds within a Self-
Assembled Coordination Cage. Chem. Asian J. 2011, 6 (7), 1839-
1847.
‡
Lehrstuhl für Bioanorganische Chemie, Department Chemie und
Pharmazie,
Egerlandstrasse 3, Erlangen 91058, Germany.
Friedrich-Alexander-Universität
Erlangen,
16.
Murase, T.; Horiuchi, S.; Fujita, M., Naphthalene
Diels−Alder in a Self-Assembled Molecular Flask. J. Am. Chem.
Soc. 2010, 132 (9), 2866-2867.
17.
Yoshizawa, M.; Tamura, M.; Fujita, M., Diels-Alder in
Funding Sources
Aqueous Molecular Hosts: Unusual Regioselectivity and
Efficient Catalysis. Science 2006, 312 (5771), 251-254.
18.
Reactivity within a confined self-assembled nanospace. Chem.
Soc. Rev. 2008, 37 (2), 247-262.
This work is part of the research programme of the
Foundation for Fundamental Research on Matter (FOM),
which is part of the Netherlands Organisation for Scientific
Research (NWO).
Koblenz, T. S.; Wassenaar, J.; Reek, J. N. H.,
19.
Dong, Z.; Luo, Q.; Liu, J., Artificial enzymes based on
supramolecular scaffolds. Chem. Soc. Rev. 2012, 41 (23), 7890-
7908.
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