Chemical
Science
EDGE ARTICLE
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article Online
View JournalLarge, heteromeaInstitut des Sciences et Inge´nierie Chim
Lausanne (EPFL), 1015 Lausanne, Switzer
+41 21-693-9305
bGZG, Abteilung Kristallographie,
Goldschmidtstr. 1, 37077 Go¨ttingen, Germa
cSwiss-Norwegian Beamline, ESRF, F-38043
dLaboratory of Crystallography, Ecole Poly
1015 Lausanne, Switzerland
eLaboratory of X-ray Crystallography, Un
Switzerland
fGlobal Phasing Ltd., Sheraton House, Castl
† Electronic supplementary information (
For ESI and crystallographic data in CI
10.1039/c4sc03046j
Cite this: DOI: 10.1039/c4sc03046j
Received 3rd October 2014
Accepted 3rd November 2014
DOI: 10.1039/c4sc03046j
www.rsc.org/chemicalscience
This journal is © The Royal Society oftallic coordination cages based on
ditopic metallo-ligands with 3-pyridyl donor
groups†
Matthew D. Wise,a Julian J. Holstein,bf Philip Pattison,cd Celine Besnard,e Euro Solari,a
Rosario Scopelliti,a Gerard Bricognef and Kay Severin*a
Ditopic N-donor ligands with terminal 4-pyridyl groups are omnipresent in coordination-based self-
assembly. The utilization of ligands with 3-pyridyl donor groups is significantly less common, because
the intrinsic conformational flexibility of these ligands tends to favor the formation of small aggregates.
Here, we show that large Pd6L12
12+ cages can be obtained by reaction of Pd(II) salts with metallo-ligands
L bearing terminal 3-pyridyl groups. The easy-to-access metallo-ligands contain an Fe(II) clathrochelate
core. These sterically demanding clathrochelate complexes prevent the formation of smaller aggregates,
which is observed for less bulky analogous building blocks. The cages were shown to bind BF4

 and
BPh4

 anions in aqueous solvent mixtures, whilst the lateral size of the clathrochelate significantly affects
their guest encapsulation behavior.Introduction
Coordination-based self-assembly is underpinned by a set of
well-established design principles. These geometrical tenets
have enabled chemists to rationally target molecular architec-
tures possessing an enormous range of structural and func-
tional characteristics.1,2 The directional bonding approach is
perhaps the most intuitive design strategy.1g,3 This approach
entails the combination of donor (ligand) and acceptor (metal
complex) units, the geometries of which determine the struc-
ture of the assembly formed. A fundamental requirement of this
strategy is that these building blocks are shape-persistent;
possessing conformational rigidity and well-dened coordinate
vectors. The self-assembly behavior of building blocks without
these characteristics is less predictable and, consequently, their
strategic incorporation into supramolecular structures inher-
ently difficult.iques, Ecole Polytechnique Fe´de´rale de
land. E-mail: kay.severin@ep.ch; Fax:
Georg-August-Universita¨t Go¨ttingen,
ny
Grenoble, Switzerland
technique Fe´de´rale de Lausanne (EPFL),
iversity of Geneva, CH-1211-Geneva 4,
e Park Cambridge CB3 0AX, England
ESI) available. CCDC 1024735–1024740.
F or other electronic format see DOI:
Chemistry 2014Ditopic N-donor ligands with terminal 4-pyridyl groups are
amongst the most extensively exploited building blocks in the
preparation of coordination-based supramolecular assemblies.
The simplest member of this family of tectons is 4,40-bipyridine,
which has been incorporated into countless discrete1 and
polymeric self-assembled structures.3 The insertion of a linker
group between the 4-pyridyl moieties has led to ever more
elaborate assemblies.4,5 In contrast to the ubiquity of 4-pyridyl
terminated N-donor ligands, closely related 3-pyridyl termi-
nated ligands are far less common.1–3 Scheme 1 alludes to why
this is the case. The coordinate vectors of a generic ditopic
N-donor ligand L1 with terminal 4-pyridyl groups are xed,
regardless of the linking group R between the heterocycles,
provided that R is rigid. Free rotation about the R–pyridine
bond does not affect the orientation of the non-bonding sp2Scheme 1 For ditopic ligands L2 with 3-pyridyl donor groups, the
relative orientation of the coordinate vectors is more flexible than for
ligands L1 with 4-pyridyl donor groups.
Chem. Sci.
Scheme 3 Synthesis of the bipyridyl ligands 1 and 2.
Chemical Science Edge Article
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article Onlineorbitals of the N atoms (Scheme 1a). However, in the case of a
generic 3-pyridyl terminated ligand L2, rotation about this bond
changes the coordinate vectors of the pyridine N atoms
(Scheme 1b).
As a consequence of the conformational exibility of 3-pyridyl
terminated N-donor ligands, entropically favored small6 aggre-
gates are obtained upon coordination to metal ions. Several
research groups have shown that the combination of Pd2+ with
‘banana-shaped’ ligands of type L2 (a < 180) typically results in
the formation of dinuclear aggregates of the formula
[Pd2(L2)4]
4+ (Scheme 2).7,8 Fujita and co-workers have examined
the reaction of Pd2+ with linear ligands of type L2 (a¼ 180) and
observed the formation of [Pd3(L2)6]
6+ and [Pd4(L2)8]
8+
complexes.9 These results are in contrast to reactions of Pd2+
with ligands of type L1, which were found to give polynuclear
coordination cages of type [Pd12(L1)24]
24+ and [Pd24(L1)48]
48+.4
Inspection of the assemblies obtained with L2-type ligands
reveals that they all feature Pd(L2)2Pd macrocycles as part of
their structure.10 We hypothesized that increasing the steric
bulk of L2-type ligands would overcome their entropic
propensity to form small aggregates. Bulky lateral R group
substituents should disfavor Pd(L2)2Pd macrocycles and thus
result in more expanded assemblies. Below we show that this
strategy can indeed be used to access unprecedented, large
coordination cages based on ditopic 3-pyridyl ligands. In
particular, we demonstrate that clathrochelate-based metal-
loligands enable the synthesis of octahedral [Pd6(L2)12]
12+ cages
with a diameter of more than 20 A˚. Despite the lateral size of the
metalloligands, the encapsulation of reasonably large guest
molecules such as tetraphenylborate (BPh4

) is possible.Results and discussion
Bipyridyl ligands 1 and 2 were isolated in 96% and 79% yield
respectively, following a one-pot synthesis similar
to that previously described for 4-pyridyl functionalized
clathrochelates (Scheme 3).11 All the starting materials used inScheme 2 Reactions of Pd2+ with ligands of type L2 give di-, tri- and
tetranuclear aggregates, whereas large coordination cages are
obtained upon reaction with ligands of type L1.
Chem. Sci.this procedure—1,2-cyclohexanedione dixoime (nioxime) or
dimethylglyoxime, anhydrous iron(II) chloride and pyr-
idin-3-ylboronic acid—are commercially available.
Single crystal X-ray diffraction unambiguously conrmed the
formation of 1 and 2 (Fig. 1). The crystal structures reveal the
conformational exibility of the coordination vectors of these
3-pyridyl appended ligands. In 1, the two planes of the pyridine
rings are close to orthogonal (85.8). Conversely, in 2, they are
almost coplanar (7.8), yet the nonbonding sp2 orbitals of the
pyridine N atoms are essentially parallel and divergent. The
bond lengths and angles found for the trigonal prismatic Fe
core of 1 and 2 are within the range observed for other Fe-based
clathrochelate complexes.12
The inherent conformational exibility of 1 and 2makes the
prediction of the structure of an assembly comprising these
building blocks difficult, even when combined with a metal
acceptor of well-dened geometry, such as a naked Pd2+ ion
(square planar geometry). As outlined above, we envisaged that
the considerable lateral steric bulk of 1 and 2 would play a
structure-directing role and prevent the formation of macrocy-
clic Pd(L2)2Pd motifs. Consequently, we anticipated that larger
cage structures could be formed by combination of 1 or 2 and a
naked Pd2+ ion, rather than small aggregates.
NMR-scale experiments were subsequently undertaken to
investigate this hypothesis. A solution of [Pd(CH3CN)4](BF4)2 inFig. 1 Molecular structures of clathrochelate-based bipyridyl ligands 1
(left) and 2 (right) as determined by X-ray crystallography. Color
coding: C: gray, B: green, Fe: orange, N: blue, O: red. Hydrogen atoms
and solvent molecules are omitted for clarity.
This journal is © The Royal Society of Chemistry 2014
Fig. 2 Molecular structure of cages 5 (top) and 6 (bottom) determined
by X-ray crystallography. Color coding: C: gray, B: green, Fe: orange,
N: blue, O: red, Pd: cyan. Anions and hydrogen atoms are omitted for
clarity.
Edge Article Chemical Science
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article Onlineacetonitrile-d3 was added to two equivalents of solid 1 or 2, both
of which are poorly soluble in acetonitrile-d3 at room temper-
ature, giving a pale yellow suspension. These samples were then
heated at 70 C and 1H NMR spectra were recorded periodically.
Over time, the reaction mixtures progressively became less
turbid and turned red. Aer 3 hours, neither solution contained
any precipitate and a single set of sharp peaks was observed in
the 1H NMR spectrum in both cases, suggesting the formation
of a single highly symmetric, discrete species (ESI, Fig. S19 and
S20†). The syntheses were subsequently performed on a
preparative scale, without deuterated solvent (Scheme 4). The
ESI-MS spectra of the products show major peaks which can be
attributed to complexes of the formula (Pd6(L2)12) (BF4)n
12
n+
(n¼ 4–6, L2¼ 1 or 2, ESI Fig. S1 and S2†). This result conrmed
that higher order assemblies (3, 4) had indeed been formed
from 1 and 2 respectively, rather than small aggregates. The
complexes 5 and 6 were prepared in an analogous fashion by
heating a suspension of 1 or 2 and Pd(NO3)2(H2O)n in a 5 : 1
mixture of acetonitrile : water for 2 hours at 70 C. The 1H NMR
spectra once more showed a single set of signals for each
product and ESI-MS conrmed the molecular formulas of the
cations to be [(Pd6(1)12)]
12+ and [(Pd6(2)12)]
12+ (ESI, Fig. S3 and
S4†). Isolation of all complexes was achieved by precipitation
with diethyl ether (isolated yields: 82–94%).
Single crystals of 3 suitable for X-ray diffraction were grown
by diffusion of diethylether into a solution of the assembly in
acetonitrile, whilst those of 5 and 6 were grown by layering an
acetonitrile solution onto toluene. Synchrotron radiation was
required to obtain diffraction data of sufficient quality, which
were collected at the Swiss Norwegian Beamline at ESRF Gre-
noble. Assemblies of this size pose a number of difficulties due
in part to their extensive inherent disorder and high solvent
content within the crystal. Synchrotron radiation mitigates
some of these difficulties, but we have also employed a series of
carefully and rigorously adapted macromolecular renement
techniques13 in order to build a molecular model (see ESI† for
details).
Fig. 2 shows the molecular structures of 5 and 6 in the crystal
(the structure of 3 is similar to that of 5 and thus not shown). In
all structures, the six Pd2+ ions of the assembly form an octa-
hedron of close to regular geometry, with Pd–Pd distances of
2.19–2.32 nm across the body of the framework, and 1.52–1.63Scheme 4 Synthesis of the cages 3–6.
This journal is © The Royal Society of Chemistry 2014nm within each triangular face. The internal angles of the facial
triangles vary from 57.3 to 61.4. The structural regularity of
the Pd framework is not, however, reected in the conformation
of the bridging ligands themselves. In 5, the planes of the
pyridine rings of the six ligands along the edges of two opposing
faces of the octahedral framework deviate signicantly from
parallel (plane dihedral angles 90.0, 89.2 and 66.8). In
contrast, the planes of the pyridine rings of the remaining six
ligands are much closer to parallel (20.6, 9.3 and 13.7). The
situation is yet more disordered in the cases of 3 and 6, where a
range of dihedral angles between pyridine rings within each
clathrochelate is observed (10.8–89.9). This illustrates the
intrinsic conformational exibility of ligands of the type L2.
Their variable coordination vectors determine the most ener-
getically favorable conformation of the assembly as a whole,
and enable this arrangement to be attained.
However, the different conformations adopted by 1 and 2 in
the self-assembled architectures 3–6 are not manifested in the
solution phase NMR spectra at room temperature. Only one set
of peaks is visible, implying that the pyridyl rings of the ligandsChem. Sci.
Chemical Science Edge Article
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article Online1 and 2, as well as the tris(dioxime) clathrochelate core, undergo
rapid conformational changes (on the NMR timescale). The 1H
NMR spectra of 3 and 4 were also recorded at 233 K (CD3CN).
Signicant line broadening was observed in all cases (ESI,
Fig. S23 and S24†). The extent of line broadening was far greater
in the case of 4 than 3. This result is unsurprising, given the
bulky cyclohexyl substituents of ligand 2 impose a higher steric
barrier to rotation than the relatively small methyl substituents
of ligand 1.
The octahedral cages possess internal void space, which is
largely occupied by solvent molecules and anions (both ordered
and disordered) in the crystal. The X-ray structures of 3, 5 and 6
show NO3

 or BF4

 anions in interior binding pockets adjacent
to the Pd2+ ions at the vertices of the octahedral assemblies. The
presence of close anion–Pd contacts is in line with what has
been observed for many cages of type [Pd2(L2)4]
4+.7 Simple
geometric approximations reveal the volume of the octahedra
described by the six Pd2+ ions in 3, 5 and 6 to be 5.2 nm3.
However, much of the interior volume of the assembly is
occupied by clathrochelate oxime substituents.14 The inuence
of the lateral size of the clathrochelate complexes over the void
volume within each assembly was quantied by VOIDOO
calculations (see ESI† for details).15 In the solid state, assembly
3 possesses a cavity volume of 1.4 nm3 or 1.8 nm3 (two inde-
pendent cages found in the asymmetric unit of the crystal
structure), cage 5 a cavity volume of 1.3 nm3 and cage 6 a much
smaller cavity volume of 1.1 nm3. From these values it is clear
that it is not only the oxime substituents that signicantly affect
the internal space within each assembly, but also the confor-
mation of the clathrochelate metalloligands. However, given the
dynamic and uxional nature of these cages evidenced by 1H
NMR, this conformational inuence was not expected to
contribute to the solution phase void volume, and hence guest
binding behavior, of assemblies 3–6. Any differences in solution
phase behavior can be attributed to the oxime substituents
alone. To investigate whether oxime steric bulk would inuence
the kinetics and thermodynamics of guest binding, 19F NMR
spectra of 3 and 4 were recorded at 298 K in acetonitrile-d3. A
single peak was observed at 
150.55 ppm for the BF4
 anion in
3, whereas peaks at 
146.37 ppm and 
151.98 ppm were
observed in the case of 4 (referenced to hexauorobenzene at

164.90 ppm). These data suggest that the rate of exchange
between internal and external BF4

 is fast on the NMR time-
scale at 298 K in the case of 3 (one signal), but slow in the case of
4 (two signals). 19F NMR spectra of 3 and 4 were subsequently
recorded over a range of temperatures (see ESI, Fig. S25 and
S26†). These experiments revealed a coalescence temperature of
approximately 255 K for the BF4

 anion signals of 3, and 345 K
for those of 4. The difference of 90 K corresponds to a difference
of 16 kJ mol
1 for the activation free energy16 of the anion
exchange process and neatly illustrates one key characteristic of
clathrochelate-based building blocks in general—the ease with
which we can modulate their steric bulk.
In addition to the anion binding sites situated adjacent to
the Pd2+ metal centers, cages 3–6 possess a central cavity. The
internal environment of this cavity is hydrophobic due to the
methyl or cyclohexyl substituents of the clathrochelate ligands,Chem. Sci.yet the overall charge of the cages is 12+. Consequently, we
expected coulombic interactions and the hydrophobic effect to
dominate the guest binding behavior of assemblies 3–6.
Therefore, the lipophilic tetraphenylborate (BPh4

) anion
appeared to be a potentially suitable guest molecule. The BPh4


anion was of particular interest not only given its perceived size
and electrostatic match, but also the limited number of host
complexes that have been found to bind BPh4

 as a guest. To
the best of our knowledge, only certain cyclodextrins,17 cav-
itands,18 liposomes19 and the external face of a metal-
losupramolecular cube20 have been observed to associate with
BPh4

 in a host—guest manner.
Complexation studies with cage 4 were hampered by the
formation of precipitates upon addition of NaBPh4, and ulti-
mately abandoned. However, addition of one equivalent of
NaBPh4 to 3 (0.62 mM) in CD3CN did not lead to precipitation,
and signicant changes in the 1H NMR signals of both species
were apparent.21 Two sets of peaks were immediately visible for
the protons of the phenyl groups of the anionic guest, and a new
set of signals was also observed for aromatic protons and
methyl groups of the clathrochelate ligands. These observations
were consistent with the formation of a host—guest complex
between the cage and the BPh4

 anion, the rate of exchange of
bound and unbound BPh4

 being slow on the NMR timescale.
To conrm the encapsulation of the BPh4

 anion within the
interior cavity of 3, DOSY and NOESY NMR experiments were
performed. DOSY NMR revealed a common diffusion coefficient
(4.94 10
6 cm2 s
1) for the assembly and one of the two sets of
BPh4

 protons (ESI, Fig. S40–S43†), whilst NOESY cross peaks
were observed between the CH3 groups of the clathrochelate
oxime ligand and the same set of BPh4

 peaks (ESI, Fig. S46–
S49†).
The apparent association constant for the complexation of
BPh4

 by 3 was calculated through integration of the NMR
signals corresponding to bound and unbound guest across a
range of concentrations, using a 1 : 1 binding model (see ESI†
for details). The resulting value is Ka ¼ 2.4(0.3)  103 M
1. We
subsequently recorded the 1H NMR spectra of 3 in the presence
of one equivalent of NaBPh4 in a 2 : 1 mixture of CD3CN and
D2O, and a 1 : 1 mixture of CD3CN and CDCl3 in order to
elucidate the effect of solvent polarity upon BPh4

 binding. In
2 : 1 CD3CN : D2O, the binding constant was calculated to be of
the order of 105 M
1, whereas in 1 : 1 CD3CN : CDCl3, the
intensities of the peaks corresponding to bound BPh4

 were too
low to integrate reliably. The large increase in binding affinity
observed upon changing the solvent from neat CD3CN to the
more polar 2 : 1 CD3CN : D2O mixture, as well as the dramatic
drop observed in the much less polar 1 : 1 CD3CN : CDCl3
mixture, enforces the hypothesis that the hydrophobic effect
plays a signicant role in guest binding. These apparent asso-
ciation constants take into account not only the encapsulation
of BPh4

 by 3, but also the thermodynamically unfavorable
concomitant ejection of internal BF4

. Consequently, the
affinity of 3 for BPh4

 is, in isolation, presumably greater than
the composite association constant recorded as discussed
above.This journal is © The Royal Society of Chemistry 2014
Edge Article Chemical Science
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article OnlineEncapsulation of BPh4

 by 3 was unambiguously
conrmed by single crystal X-ray crystallography. A ten-
fold excess of NaBPh4 was added to a solution of 3 in 2 : 1
CD3CN : D2O, and from the resulting suspension single
crystals of a mixed salt (7) containing both BPh4

 and BF4


anions were isolated. Despite the relatively poor quality of the
diffraction data, due to the size and complexity of the struc-
ture, a sufficient solution was obtained, which unquestion-
ably established the connectivity within the [Pd6112]
assembly, as well as the presence of encapsulated BPh4

.
Unsurprisingly, it was impossible to locate all BF4

 and
BPh4

 anions due to the extent to which they are disordered,
hence precise formulation of this salt cannot be undertaken
using the X-ray diffraction data. Rather, the general formula
[BPh4@Pd6112][BF4]m[BPh4]n, where m + n ¼ 11, must be used
to describe 7. Two independent cages were found in the
asymmetric unit, each of which contained a single encapsu-
lated BPh4

 (see ESI, Fig. S31†). One of the two independent
cages additionally contained three ordered BF4

 (Fig. 3),
whilst a single ordered BF4

 was located in the second. The
positions of the different anions in the former illustrate the
differences in size of the two interior cavities of 3—the
smaller BF4

 anions occupy binding pockets adjacent to the
Pd2+ vertices of one face of the octahedral framework, whilst
the non-coordinating BPh4

 resides within the larger central
cavity of the assembly. Two of the phenyl groups of BPh4

 sit
snugly between the methyl substituents of the clathrochelate
oxime ligands of two neighboring faces of the [Pd6112]
12+
assembly. This conformation alludes to the contribution of
hydrophobic interactions to BPh4

 encapsulation, and is
consistent with the upeld change in chemical shi observed
for the protons of the CH3 groups of the oxime substituents as
they are exposed to the diamagnetic ring current of the
phenyl rings (see ESI, Fig. S37†).Fig. 3 Part of the X-ray crystal structure of 7, highlighting the
encapsulated BF4

 (yellow-green) and BPh4

 (magenta) anions.
External anions, hydrogen atoms and solvent molecules are omitted
for clarity.
This journal is © The Royal Society of Chemistry 2014Conclusions
Herein, we have reported the syntheses and the structures of
two clathrochelate-basedmetalloligands with terminal 3-pyridyl
groups (1 and 2). Reactions of these ligands with Pd2+ afford
large octahedral coordination cages (3–6), which were compre-
hensively characterized (including crystallographic analysis for
three of the four cages). The formation of octahedral Pd cages
from ditopic ligands containing 3-pyridyl groups is unprece-
dented. Typically, conformationally exible ligands with
terminal 3-pyridyl groups give rise to small aggregates (Scheme
2). In our case, the lateral size of the metalloligands prevents the
formation of macrocyclic Pd(L2)2Pd structures. This enthalpic
effect (steric hindrance) is sufficient to overcome the entropi-
cally driven propensity of a coordination-based supramolecular
system to form small aggregates. Consequently, larger octahe-
dral structures are obtained, the assembly of which is favored to
such an extent that no side products are observed. Despite the
fact that we have used steric effects to enlarge the assembly, we
were still able to obtain cages with rather large cavities. Notably,
cage 3 was found to bind the ‘non-coordinating’22 anion BPh4


with a solvent-dependent association constant of the order
of 105 M
1.
Our work also highlights the advantageous characteristics of
clathrochelate complexes as building blocks for supramolecular
chemistry.11,23 These complexes are straightforward to synthe-
size and their lateral size and functionality24 can be modulated
by the boronic acid capping groups and the oxime substituents.
The ability to modify the structure of the metalloligands
without substantial synthetic efforts represents an important
advantage for implementing or optimizing a certain function of
the nal assembly. As a proof-of-principle study, we have shown
that the kinetics of BF4

 exchange are strongly affected by the
nature of the oxime-derived side chain (methyl vs. cyclohexyl).
We believe that judicious design of clathrochelate building
blocks will enable many more structurally and functionally
novel self-assembled architectures to be obtained, and we are
continuing to pursue the applications of these ligands in
coordination-based self-assembly.
Acknowledgements
The research leading to these results has received funding from
the People Programme (Marie Curie Actions) of the European
Union's Seventh Framework Programme FP7/2007–2013/under
REA grant agreement no 264645 (MDW and JJH). We thank
Mathieu Marmier, EPFL, for help with the graphical material.
Notes and references
1 For selected recent review articles about molecularly dened
assemblies see: (a) S. Mukherjee and P. S. Mukherjee, Chem.
Commun., 2014, 50, 2239; (b) M. D. Ward and P. R. Raithby,
Chem. Soc. Rev., 2013, 42, 1619; (c) J. G. Hardy, Chem. Soc.
Rev., 2013, 42, 7881; (d) N. J. Young and B. P. Hay, Chem.
Commun., 2013, 49, 1354; (e) T. K. Ronson, S. Zarra,
S. P. Black and J. R. Nitschke, Chem. Commun., 2013, 49,Chem. Sci.
Chemical Science Edge Article
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article Online2476; (f) H. Amouri, C. Desmarets and J. Moussa, Chem. Rev.,
2012, 112, 2015; (g) R. Chakrabarty, P. S. Mukherjee and
P. J. Stang, Chem. Rev., 2011, 111, 6810; (h) M. J. Wiester,
P. A. Ulmann and C. A. Mirkin, Angew. Chem., Int. Ed.,
2011, 50, 114.
2 For selected recent review articles about polymeric
assemblies see: (a) W. Lu, Z. Wei, Z.-Y. Gu, T.-F. Liu,
J. Park, J. Park, J. Tina, M. Zhang, Q. Zhang, T. Gentle III,
M. Bosch and H.-C. Zhou, Chem. Soc. Rev., 2014, 43, 5561–
5593; (b) V. Guillerm, D. Kim, J. F. Eubank, R. Luebke,
X. Liu, K. Adil, M. S. Lah and M. Eddaoudi, Chem. Soc.
Rev., 2014, 43, 6141; (c) H. Furukawa, K. E. Cordova,
M. O'Keeffe and O. M. Yaghi, Science, 2013, 341, 974; (d)
T. R. Cook, Y.-R. Zheng and P. J. Stang, Chem. Rev., 2013,
113, 734; (e) W. Xuan, C. Zhu, Y. Liu and Y. Cui, Chem. Soc.
Rev., 2012, 41, 1677; (f) N. N. Adarsh and P. Dastidar,
Chem. Soc. Rev., 2012, 41, 3039; (g) F. A. Almeida,
J. Klinowski, S. M. F. Vilela, J. P. C. Tome´, J. A. S. Cavaleiro
and J. Rocha, Chem. Soc. Rev., 2012, 41, 1088; (h) N. Stock
and S. Biswas, Chem. Rev., 2012, 112, 933.
3 B. H. Northrop, D. Chercka and P. J. Stang, Tetrahedron,
2008, 64, 11495.
4 Review: K. Harris, D. Fujita and M. Fujita, Chem. Commun.,
2013, 49, 6703.
5 Selected examples: (a) S.-L. Huang, Y.-J. Lin, T. S. A. Hor and
G.-X. Jin, J. Am. Chem. Soc., 2013, 135, 8125; (b) D. Fujita,
K. Suzuki, S. Sato, M. Yagi-Utsumi, Y. Yamaguchi,
N. Mizuno, T. Kumasaka, M. Takata, M. Noda,
S. Uchiyama, K. Kato and M. Fujita, Nat. Commun., 2012, 3,
1093; (c) J. Bunsen, J. Iwasa, P. Bonakdarzadeh, E. Numata,
K. Rissanen, S. Sato and M. Fujita, Angew. Chem., Int. Ed.,
2012, 51, 3161; (d) Q.-F. Sun, T. Murase, S. Sato and
M. Fujita, Angew. Chem., Int. Ed., 2011, 50, 10318; (e)
Q.-F. Sun, J. Iwasa, D. Ogawa, Y. Ishido, S. Sato, T. Ozeki,
Y. Sei, K. Yamaguchi and M. Fujita, Science, 2010, 328, 1144.
6 The notion ‘small’ refers here to the formation of aggregates
containing a small number of building blocks. They can be
large in terms of size if large ligands are employed.
7 Review: M. Han, D. M. Engelhard and G. H. Clever, Chem.
Soc. Rev., 2014, 43, 1848.
8 Selected examples: (a) J. E. M. Lewis, A. B. S. Elliott,
C. J. McAdam, K. C. Gordonab and J. D. Crowley, Chem.
Sci., 2014, 5, 1833; (b) C. Desmarets, G. Gontard,
A. L. Cooksy, M. N. Rager and H. Amouri, Inorg. Chem.,
2014, 53, 4287; (c) M. Han, R. Michel, B. He, Y.-S. Chen,
D. Stalke, M. John and G. H. Clever, Angew. Chem., Int. Ed.,
2013, 52, 1319; (d) G. H. Clever, W. Kawamura, S. Tashiro,
M. Shiro and M. Shionoya, Angew. Chem., Int. Ed., 2012, 51,
2606; (e) J. E. M. Lewis, E. L. Gavey, S. A. Cameron and
J. D. Crowley, Chem. Sci., 2012, 3, 778; (f) M. Han, J. Hey,
W. Kawamura, D. Stalke, M. Shionoya and G. H. Clever,
Inorg. Chem., 2012, 51, 9574; (g) N. Kishi, Z. Li, K. Yoza,
M. Akita and M. Yoshizawa, J. Am. Chem. Soc., 2011, 133,
11438; (h) P. Liao, B. W. Langloss, A. M. Johnson,
E. R. Knudsen, F. S. Tham, R. R. Julian and R. J. Hooley,
Chem. Commun., 2010, 46, 4932; (i) G. H. Clever, S. Tashiro
and M. Shionoya, Angew. Chem., Int. Ed., 2009, 48, 7010.Chem. Sci.9 D. K. Chand, K. Biradha, M. Kawano, S. Sakamoto,
K. Yamaguchi and M. Fujita, Chem.–Asian J., 2006, 1, 82.
10 The reaction of linear ligands of type L2 with cis-blocked (L-
L)Pd2+ complexes gives also (L-L)Pd(L2)2Pd(L-L)
macrocycles. See: M.-E. Moon, H.-J. Lee, B.-S. Ko and
K.-W. Chi, Bull. Korean Chem. Soc., 2007, 28, 311.
11 M. D. Wise, A. Ruggi, M. Pascu, R. Scopelliti and K. Severin,
Chem. Sci., 2013, 4, 1658.
12 Recent examples include: (a) O. A. Varzatskii, S. V. Shul'ga,
A. S. Belov, V. V. Novikov, A. V. Dolganov,
A. V. Vologzhanina and Y. Z. Voloshin, Dalton Trans., 2014,
DOI: 10.1039/c4dt01557f; (b) O. A. Varzatskii,
I. N. Denisenko, A. S. Belov, A. V. Vologzhanina,
Y. N. Bubnov, S. V. Volkov and Y. Z. Voloshin, Inorg. Chem.
Commun., 2014, 44, 134; (c) V. V. Novikov, I. V. Ananyev,
A. A. Pavlov, M. V. Fedin, K. A. Lyssenko and
Y. Z. Voloshin, J. Phys. Chem. Lett., 2014, 5, 496; (d)
O. A. Varzatskii, I. N. Denisenko, S. V. Volkov,
A. V. Dolganov, A. V. Vologzhanina, Y. N. Bubnov and
Y. Z. Voloshin, Inorg. Chem. Commun., 2013, 33, 147; (e)
O. A. Varzatskii, I. N. Denisenko, S. V. Volkov, A. S. Belov,
A. V. Dolganov, A. V. Vologzhanina, V. V. Novikov,
Y. N. Bubnov and Y. Z. Voloshin, Eur. J. Inorg. Chem., 2013,
3178.
13 (a) A. Thorn, B. Dittrich and G. M. Sheldrick, Acta Cryst. A,
2012, 68, 448; (b) O. S. Smart, T. O. Womack, C. Flensburg,
P. Keller, W. Paciorek, A. Sharff, C. Vonrhein and
G. Bricogne, Acta Cryst. D, 2012, 68, 368.
14 For examples of octahedral Pd cages see: (a) C. Gu¨tz,
R. Hovorka, C. Klein, Q.-Q. Jiang, C. Bannwarth,
M. Engeser, C. Schmuck, W. Assenmacher, W. Mader,
F. Topic´, K. Rissanen, S. Grimme and A. Lu¨tzen, Angew.
Chem., Int. Ed., 2014, 53, 1693; (b) K. Li, L.-Y. Zhang,
C. Yan, S.-C. Wei, M. Pan, L. Zhang and C.-Y. Su, J. Am.
Chem. Soc., 2014, 136, 4456; (c) K. Suzuki, M. Tominaga,
M. Kawano and M. Fujita, Chem. Commun., 2009, 1638.
15 G. J. Kleywegt and T. A. Jones, Acta Crystallogr., Sect. D: Biol.
Crystallogr., 1994, 50, 178–185.
16 J. Sandstro¨m, Dynamic Nmr Spectroscopy, Academic Press,
1982.
17 (a) M. D. Johnson and V. C. Reinsborough, Aust. J. Chem.,
1992, 45, 1961; (b) T. Nhujak and D. M. Goodall,
Electrophoresis, 2001, 22, 117.
18 S. S. Zhu, H. Staats, K. Brandhorst, J. Grunenberg, F. Gruppi,
E. Dalcanale, A. Lu¨tzen, K. Rissanen and C. A. Schalley,
Angew. Chem., Int. Ed., 2008, 47, 788.
19 H. Osanai, T. Ikehara, S. Miyauchi, K. Shimono,
J. Tamogami, N. Nara and N. Kamo, J. Biophys. Chem.,
2013, 4, 11.
20 W. J. Ramsay and J. R. Nitschke, J. Am. Chem. Soc., 2014, 136,
7038.
21 Binding studies were not performed with cage 5 and 6
because they display a lower solubility compared to 3 and 4.
22 Receptors for weakly-coordinating anions are described in:
(a) S. Lee, C.-H. Chen and A. H. Flood, Nat. Chem., 2013, 5,
704; (b) Y. R. Hristova, M. M. J. Smulders, J. K. Clegg,
B. Breiner and J. R. Nitschke, Chem. Sci., 2011, 2, 638.This journal is © The Royal Society of Chemistry 2014
Edge Article Chemical Science
O
pe
n 
A
cc
es
s A
rti
cl
e.
 P
ub
lis
he
d 
on
 1
1 
N
ov
em
be
r 2
01
4.
 D
ow
nl
oa
de
d 
on
 1
9/
11
/2
01
4 
16
:2
3:
20
. 
 
Th
is 
ar
tic
le
 is
 li
ce
ns
ed
 u
nd
er
 a
 C
re
at
iv
e 
Co
m
m
on
s A
ttr
ib
ut
io
n 
3.
0 
U
np
or
te
d 
Li
ce
nc
e.
View Article Online23 (a) Y.-Y. Zhang, Y.-J. Lin and G.-X. Jin, Chem. Commun., 2014,
50, 2327; (b) M. Pascu, M. Marmier, C. Schouwey,
R. Scopelliti, J. J. Holstein, G. Bricogne and K. Severin,
Chem.–Eur. J., 2014, 20, 5592.This journal is © The Royal Society of Chemistry 201424 For clathrochelate complexes with different functional
groups see: E. G. Lebed, A. S. Belov, A. V. Dolganov,
A. V. Vologzhanina, A. Szebesczyk, E. Gumienna-Kontecka,
H. Kozlowski, Y. N. Bubnov, I. Y. Dubey and
Y. Z. Voloshin, Inorg. Chem. Commun., 2013, 30, 53.Chem. Sci.