Self-Assembly and Host-Guest Interactions of Pd3L2Metallo-cryptophanes with Photoisomerizable Ligands

Article abstract of DOI:10.1021/acs.inorgchem.1c01297

New photoswitchable pyridyl-azo-phenyl-decorated tripodal host ligands (Laz) that belong to the cyclotriveratrylene family have been synthesized, and their photoswitching behavior and crystal structures determined. The latter includes a remarkable 7-fold

Full text of DOI:10.1021/acs.inorgchem.1c01297

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Self-Assembly and Host−Guest Interactions of Pd3L2 Metallo-
cryptophanes with Photoisomerizable Ligands
Edward Britton, Richard J. Ansell, Mark J. Howard, and Michaele J. Hardie*
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ABSTRACT: New photoswitchable pyridyl-azo-phenyl-decorated
tripodal host ligands (Laz) that belong to the cyclotriveratrylene
family have been synthesized, and their photoswitching behavior
and crystal structures determined. The latter includes a remarkable
7-fold Borromean-weave entanglement of π−π stacked layers.
Trigonal bipyramidal {[Pd(en)]3(Laz)2}6+ metallo-cryptophanes
(en = ethylenediamine) were formed from these and a previously
known pyridyl-azo-phenyl-decorated tripodal host ligand. These
coordination cages dissociate at low concentrations and are less
robust to photoswitching of the Laz ligands than were previously
reported Ir(III)-linked metallo-cryptophanes with similar ligands, reflecting the greater lability of the Pd−N bonds. The
{[Pd(en)]3(Laz)2}6+ cages all act as hosts, binding octyl sulfate anions, or N-[2-(dimethylamino)ethyl]-1,8-naphthalimide in a
dimethyl sulfoxide solution.
nicotinoyl17 donor groups. The use of chelating ligands as
INTRODUCTION
Coordination cages or metallo-cages are three-dimensional
■
coordination-site protecting groups is a common approach to
controlling assembly of metallo-cages.18 Bis-N-heterocyclic
assemblies of metal cations and bridging ligands with inherent
internal space.1 Cages may act as host assemblies and bind
carbene chelate ligands have also been successfully employed
as protecting ligands for Pd3L2 metallo-cryptophanes.19
guest molecules or ions through solvophobic effects and
noncovalent interactions. Their binding properties lead to a
Interestingly, a {[Pd(en)]3L2]6+ metallocryptophane (en =
ethylenediamine) is metastable and undergoes a spontaneous
rearrangement in solution to a larger [Pd6L8]12+ stella
octangula cage,19 behavior also reported for a different class
of Pd3L2 cages.20 Other metallo-cryptophanes include
luminescent {[Ir(C∧N)2]3L2}3+ cages in which C∧N is a
cyclometalling ligand.10,21 We have recently reported a series
of such {[Ir(C∧N)2]3(Laz)2}3+ cages in which the Laz ligands
are tripodal CTV analogues functionalized with photo-
isomerizable pyridyl-azo-phenyl groups, with an example
shown in Figure 1.10 Each cage contains six pyridyl-azo-phenyl
groups that are an inherent part of the cage structure.
Azobenzenes (AZB), as well as analogous azoheteroarene
species such as these, are some of the most widely used
photoswitching motifs and undergo reversible trans → cis
isomerization of the aromatic groups about the azo group.22
Remarkably, the {[Ir(C∧N)2]3(Laz)2}3+ cages show reversible
photoisomerizations without any change in composition. The
cornucopia of potential applications in sensor chemistry and
catalysis and as nanoscale reaction vessels where confinement
of reagents affects properties. The dynamic behavior of
coordination cages includes simple ligand exchange and
more complex stimulus-responsive behavior, the latter
including reconfiguration of cages according to solvent, pH,
or other chemical triggers.2 Coordination cages that are
responsive to light form another category of stimulus-
responsive cages.3−11
Our research focuses on metallo-supramolecular chemistry
of the cyclotriveratrylene (CTV) family of host molecules.
CTV-type host molecules feature a tribenzo[a,d,g]cyclononene
scaffold with a bowl conformation, an open upper rim, and a
hydrophobic binding cavity.12 Tripodal analogues of CTV with
ligand groups appended to the upper rim of the bowl are chiral
and have proved to be ideal for the self-assembly of metallo-
cages, as they have an orthogonal arrangement of metal-
binding groups and a deep cavity.13 The smallest such cages
are M3L2 metallo-cryptophanes with a trigonal bipyramidal
cage shape, noting a cryptophane is an organic cage of two
linked CTV fragments. The first examples were {[Pd-
(P∧P)]3L2}6+ metallo-cryptophanes published by Yamaguchi
and Shinkai with 4-pyridyl donor groups on the CTV ligand,
where P∧P is a chelating phosphine donor ligand.14 Other
{[Pd(P∧P)]3L2}6+ examples employ nitrile15,16 or iso-
Received: April 28, 2021
© XXXX The Authors. Published by
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[PdReL2]2+ metallamacrocycle on trans → cis photoisomeriza-
tion.23 Liu and co-workers have reported a [Pd2L4]4+ cage in
which the bridging ligand contains two pyridyl-azo-phenyl
groups. This cage completely dissociates upon photoisomeri-
zation of the ligand.4 Clever and co-workers have reported a
series of [Pd4L4]4+ coordination cages that undergo reversible
photoisomerization of a structurally inherent bridging ligand
while maintaining the integrity of the cage.5 Here the
photoswitching group is a dithienylethene (DTE) in which
the structural rearrangement is a ring-open ↔ ring-closed
process that is much less dramatic than the trans → cis
rearrangement of AZB. Other examples of cages with DTE-
based bridging ligands undergo [Pd3L6]6+ ↔ [Pd24L48]48+ cage
transformations on ring-open and ring-closed photoisomeriza-
tion,6 and this motif and cage topology switching behavior
have been incorporated into soft polymer networks.7
Wezenberg and Feringa have reported a photoresponsive
[Pd2L4]4+ coordination cage with bridging ligands based on a
molecular rotor design of overcrowded alkenes.8
Figure 1. Molecular model of the previously reported {[Ir-
(ppy)2]3(Laz-OMe)2]6+ metallo-cryptophane with a CTV-type ligand
appended with pyridyl-azo-phenyl groups, all shown in the
thermodynamically stable trans configuration.10
We report herein the synthesis of a series of new palladium-
linked metallo-cryptophanes, {[Pd(en)]3(Laz)2]6+, where Laz
includes the previously reported Laz-OMe alongside novel
variants with longer-chain ethoxy or propoxy pendant groups
on their upper rim (Scheme 1). The presence of propoxy
groups rather than methoxy groups on CTV-type ligands
affects the solubility of the ligand and has been also shown to
affect the relative stabilities of Pd6L8 cages.24 Here, we
investigate the influence of the alkyl-chain length on host−
guest properties of these metallo-cryptophanes. Palladium(II)
is a significantly more labile metal center than is iridium(III).25
Hence, the photoisomerization behavior of {[Pd-
robust nature of the cages to structure switching was in part
attributed to the chemical inertness of Ir(III) inhibiting
dissociation of the cages.10
Examples of coordination cages and two-dimensional
polygons that undergo photoisomerization fall into two
categories: those in which the photoisomerizable group is
pendant to the cage3 and those in which it is a structurally
inherent component of the cage or polygon.4−8,10,23 Lees et al.
have reported photoisomerization of a [Pd2Re2L4]4+ metallo-
supramolecular square in which L is an azo-bis(4-pyridyl)
bridging ligand, which reversibly transforms to a smaller
Scheme 1. Self-Assembly of Metallo-cryptophanes and Numbering Scheme for NMR
B
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Scheme 2. Synthesis of New Ligands
(en)]3(Laz)2}6+ species will allow us to further test whether the
kinetic inertness of the metal cage vertices is an important
factor in the structural robustness of cages with AZB switches.
phenyl arms to form a network with large open channels with
diameters of 25 Å.10 Laz-OEt crystallizes with near-C3
symmetry with all ethyl groups adopting essentially the same
conformation, and all 3-pyridylazophenyl groups are likewise in
similar trans conformations (Figure 2a). All upper rim groups
are co-planar or nearly co-planar with their corresponding
arene ring of the cyclononatriene bowl. The Laz-OEt hosts
stack into homochiral columns in the crystal lattice, adopting
an eclipsed bowl-in-bowl stacking separated by an a unit cell
parameter of 4.7068(3) Å, which is too long to indicate
formation of π−π stacking interactions. The identity of the
ligand enantiomer and bowl-up/bowl-down orientation
alternate in the crystal lattice in a checkerboard arrangement,
and small channels run along the a direction (Figure 2b and
Figure S55). These are likely occupied by solvent molecules,
but the quality of the data obtained did not allow for
refinement of solvent positions.
Unlike in Laz-OEt, each upper rim arm of Laz-OPr in the Laz-
OPr·CHCl3 complex adopts a different conformation. The
CHCl3 is an intracavity guest molecule, forming a C−H···π
interaction with one of the arene groups of the cyclononatriene
bowl (Figure 3). Each 3-pyridylazophenyl arm of Laz-OPr
forms a π−π stacking interaction with its symmetry equivalent
around an inversion center with pyridyl ring centroid and
pyridyl ring···azo centroid separations of 3.963 and 4.164 Å,
3.855 and 3.659 Å, and 4.190 and 3.626 Å, respectively. This
results in the formation of a two-dimensional (2D) hexagonal
network of Laz-OPr host molecules with 63 topology, with
alternating ligand enantiomer and bowl-up/bowl-down
orientations (Figure 4a). Within a layer of the crystal lattice,
there are seven such 2D Laz-OPr hexagonal networks. The
seven π−π stacking networks exhibit a remarkable 7-fold 2D →
2D Borromean entanglement (Figure 4). Borromean rings are
a type of topological entanglement in which three-ring
structures cannot be separated without breaking a ring but
there is no catenation or threading between the rings.
Synthetic Borromean ring assemblies can be discrete ring
assemblies or entangled networks of rings.28−35 Assemblies
with networks of infinite Borromean ring associations fall into
two broad categories: infinite chainmail arrays of Borromean
associations between discrete rings29 and Borromean entangle-
ments of 2D networks.28b,30−34 Borromean entanglement of
2D networks has been reported for coordination poly-
RESULTS AND DISCUSSION
■
Ligand Synthesis and Characterization. The new
ligands were synthesized using the same methodology that
was used for the previously reported ( )-2,7,12-trimethoxy-
3,8,13-tris(3-pyridyl-4-azophenylcarboxy)-10,15-dihydro-5H-
tribenzo[a,d,g]cyclononene, Laz-OMe.10 Ligands ( )-2,7,12-
triethoxy-3,8,13-tris(3-pyridyl-4-azophenylcarboxy)-10,15-di-
hydro-5H-tribenzo[a,d,g]cyclononene (Laz-OEt) and
( )-2,7,12-tripropoxy-3,8,13-tris(3-pyridyl-4-azophenylcar-
boxy)-10,15-dihydro-5H-tribenzo[a,d,g]cyclononene (Laz-
OPr) were synthesized in good yields by reaction of
( )-eCTG [( )-2,7,12-triethoxy-3,8,13-trimethoxy-10,15-di-
hydro-5H-tribenzo[a,d,g]cyclononatriene]26 and ( )-pCTG
[( )-2,7,12-tripropoxy-3,8,13-trimethoxy-10,15-dihydro-5H-
tribenzo[a,d,g]cyclononatriene],24 respectively, with the acid
chloride of sodium [2-(3-pyridyl)diazenyl]-benzoate (Scheme
2). Full routes taken to ( )-eCTG and ( )-pCTG are given in
the Supporting Information. Ligands were characterized by
electrospray mass spectrometry (ESMS), NMR, and ultra-
violet−visible (UV−vis) spectroscopies (Supporting Informa-
tion), all of which are consistent with the proposed structures.
An interesting feature of the ESMS spectrum is, alongside the
expected m/z peaks, the appearance of peaks corresponding to
dimeric {2L + 3H}3+ species for both Laz-OEt and Laz-OPr at
m/z 719.5977 and 747.6284, respectively. This suggests the
formation of hydrogen-bonded capsules in the gas phase.
Water-mediated hydrogen-bonded capsules of pyridyl-ap-
pended CTV analogues have been reported by Purohit and
co-workers.27
Single crystals of Laz-OEt and Laz-OPr·CHCl3 were obtained
by diffusion of diethyl ether into a saturated solution of each
ligand in chloroform. Crystals of both Laz-OEt and Laz-OPr·
CHCl3 were small and required the use of synchrotron
radiation to establish their crystal structures. Despite minor
differences in chemical composition, the three Laz ligands form
drastically different crystal structures. The crystal structure of
Laz-OMe has been previously established and featured columns
of bowl-in-bowl Laz-OMe host molecules, which interlock
through extensive π−π stacking between the 3-pyridylazo-
C
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Figure 3. Asymmetric unit of the crystal structure of Laz-OPr·CHCl3
highlighting host−guest interactions. CHCl3 shown with C colored
green. Otherwise gray for C, red for O, blue for N, yellow for Cl, and
white for H.
The UV−vis spectra of ligands Laz-OMe, Laz-OEt, and Laz-
OPr in CHCl3 are similar, each showing a strong π−π*
absorption band near 325 nm and a weak n−π* band at 450
nm. A trans → cis photoisomerization of azobenzene moieties
leads to a decrease in the intensity of the π−π* band and a
concomitant marginal increase in the intensity of the n−π*
band. Irradiation of the 30 μM chloroform solutions of each
ligand with a 30 W 365 nm lamp for a total of 60 s led to very
similar spectral changes indicative of photoisomerization,
shown for Laz-OEt in Figure 5 (see the Supporting Information
for other ligands). Irradiation beyond 60 s did not lead to
further spectral changes. Under these conditions, 52−54% of
the trans 3-pyridylazophenyl groups of each ligand were
converted to the cis isomer. The presence of three 3-
pyridylazophenyl arms per ligand means that there are four
possible isomers on photoswitching: trans−trans−trans, trans−
trans−cis, trans−cis−cis, and cis−cis−cis. The photoswitched
ligand solutions are likely to contain a mixture of these
Figure 2. Crystal structure of ligands Laz-OEt; (a) asymmetric unit of
one ligand and (b) packing diagram showing homochiral stacks. Gray
for C, red for O, and blue for N.
1
isomers. Indeed, previous H NMR studies of the photo-
switching behavior of Laz-OMe indicate that this is the case.10
{[Pd(en)]3(Laz)2}6+ Metallo-cryptophanes. Metallo-cryp-
tophane cages of the {[Pd(en)]3(Laz)2}6+ type can be
assembled for Laz-OMe (C1), Laz-OEt (C2), and Laz-OPr
(C3) by self-assembly of a 3:2 mixture of [Pd(en)(NO3)2] and
the appropriate Laz ligand in dimethyl sulfoxide (DMSO)
(Scheme 1). The use of other solvents such as acetonitrile or
nitromethane did not result in cage formation. All three cages
showed similar NMR spectra. All resonances of their 1H NMR
spectra were broadened slightly and remained relatively
straightforward, consistent with the formation of a symmetric
larger species such as metallo-cryptophane, shown for complex
C1 in Figure 6 (see the Supporting Information for other
complexes). In each complex, signals for the two protons
situated ortho to the pyridyl nitrogen exhibited a downfield
shift from ∼9.2 to 9.6 ppm (He) and from ∼8.75 to 9.15 ppm
(Hb), consistent with binding of the pyridyl nitrogen to the
palladium center. Cages C1 and C2 were further characterized
by 13C{1H} NMR, which reveals a consistent number of peaks
with the proposed structure, and 2D NMR techniques COSY,
HSQC, and HMBC, allowing for the complete assignment of
all proton environments (Figures S15−S18 and S23−S26).
mers28b,30 and hydrogen-bonded,31,32 halogen-bonded,33 and
argentophilic34 networks. Borromean entanglement of 2D
layers within a self-entangled 3D coordination polymer is also
known.35 A majority of examples involve undulating 2D
networks of 63 topology as shown here. Known one-
dimensional (1D) → 2D and 2D → 2D Borromean
entanglements generally show 3-fold entanglement of net-
works. Examples of 2D → 3D entanglement also feature a
traditional Borromean relationship in which each ring within a
network is entangled with two others. To the best of our
knowledge, however, the 7-fold entanglement observed in Laz-
OPr·CHCl3 is only the second example of such a higher-order
Borromean entanglement of networks. The first was also a 7-
fold Borromean entanglement of a 2D 63 network, in this case
a hydrogen-bonded network.32 Borromean chainmail structure
is also of higher order and features discrete but interlocked
M6L6 metallamacrocyles that also involved a tripodal CTG
derivative as the ligand.29
D
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Figure 4. From the crystal structure of Laz-OPr·CHCl3. (a) π−π stacking interactions forming a 2D network of 63 topology. (b) Detail showing
seven entangled π−π stacking networks within a layer. (c) Connectivity diagram highlighting the 7-fold Borromean entanglement of networks with
a single Borromean ring association between these network highlighted in panel d.
The 1H−1H NOESY NMR spectrum obtained for C2 (Figure
6b) displays the expected cross-coupling between the amine
protons on the palladium ethylenediamine complex and the
ortho pyridyl protons on the ligand (He/b), which would be in
the proximity in the proposed structure. Similar cross-
signals that align perfectly with the free ligands, albeit
somewhat broadened (Figures 6a and Figures S22 and S29).
This may indicate exchange between the free ligand and the
metallo-cryptophane. There were no peaks in the spectra that
could be attributed to any intermediate species such as
[M2L2]4+. This implies that while the cryptophane species may
be in rapid exchange with its constituent parts, the process of
metallo-cryptophane formation becomes progressively more
energetically favorable once formation has started with an
[ML]+ species. This behavior has been observed for self-
assembled systems previously, for example, Lehn’s helicates.36
1
couplings were seen in H−1H NOESY spectra of samples of
each of the cages obtained during host−guest studies (Figures
1
S43−S45). H DOSY NMR spectra of each of C1−C3 were
also consistent with cage formation (Figures S19, S27, and
S30). ESMS run under standard dilution conditions did not
show cages in solution due to cage dissociation at low
concentrations, with the spectra dominated by free ligands
(Figures S32 and S33). We could obtain an ESMS spectrum
for a concentrated solution of C1 that gave the expected 6+
peak at m/z 428.1710 (calculated m/z 428.4311 for {[Pd-
(en)]3(Laz-OMe)2}6+) (Figure S31).
1
The H NMR spectra of C1−C3 did not sharpen, or change
appreciably, on standing for several months. The latter is
notable, as our previous studies of {[Pd(en)]3(Lpy)2}6+ cages
in which Lpy is an isonicotinoyl-appended CTG ligand revealed
a rearrangement to a larger stella octangula Pd6L8 cage on
standing in solution for 2 weeks.24 Furthermore, {[Ir-
(C∧N)2]3(Lpy)2}3+ cages exhibit spectral sharpening associated
1
Closer analysis of the H NMR spectra of C1−C3 revealed
that, alongside the major peaks that can be attributed to the
metallo-cryptophane, there were a number of much smaller
E
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intact {[Pd(en)]3(Laz-OMe)2}6+ cage upon photoirradiation
should be observable as a change in drift time with anticipated
broadening of the distribution curve. This was not observed,
and peaks corresponding to the {[Pd(en)]3(Laz-OMe)2}6+ cage
were very similar for the parent and irradiated solutions
(Figures S34 and S35). Thus, there is no evidence of the
presence of a {[Pd(en)]3(Laz-OMe)2}6+ cage with any Laz-
OMe ligands in the cis, or partial cis, configuration, and the
observed metallo-cryptophane is an unswitched all-trans cage.
Host−Guest Studies. A range of other neutral and anionic
molecules were screened for host−guest interactions with the
metallo-cryptophanes, including fullerenes, borane salt
Cs2B12F12, sodium octyl sulfate, haloalkanes, and a naph-
thalamide derivative. Fullerenes, in particular, are widely
documented to form host−guest association with CTV and
many of its analogues or derivatives.39 Of the potential guests
tried, only sodium octyl sulfate [SOS (Chart 1)] and
naphthalimide derivative N-[2-(dimethylamino)ethyl]-1,8-
naphthalimide [nap (Chart 1)] exhibited any evidence of
forming host−guest interactions with the metallo-crypto-
phanes.
Figure 5. UV−vis spectrum of Laz-OEt (30 μM, CHCl3) upon
irradiation with 365 nm light. The decreasing intensity of the π−π*
band at 325 nm and the increasing intensity of the n−π* band at
∼440 nm are indicative of trans → cis isomerization.
We have previously reported the 1:2 host:guest (H:G)
binding of alkyl sulfate surfactant anions by the [Pd6(Lpy)8]12+
stella octangula cage.40 Jung and co-workers have recently
reported a distinct Pd6L8 cage that binds a range of alkyl sulfate
surfactants in which the cage shows a breathing-type flexibility
induced by guest binding.41 Surfactant anions have an anionic
headgroup capable of electrostatic interactions with the
palladium centers, and a hydrophobic tail capable of C−
H···π interactions with the walls of the cage. The binding
behavior of C1−C3 in a DMSO solution to SOS was
investigated via binding experiments that were performed
with guest concentrations ranging from 1.0 to 40 mM. While
this is below the critical micelle concentration for SOS,42,43
self-titration experiments with SOS in DMSO monitored by
1H NMR did show minor chemical shift changes indicative of
some aggregation at these concentrations (Figure S36).
Titration of a solution of SOS into a 3.85 mM solution of
each of the metallo-cryptophane cages C1−C3 resulted in
distinct 1H NMR chemical shift changes for all proton
environments of the SOS along with some proton environ-
ments of the cages. There was only one set of signals for the
SOS guest indicating those bound and unbound guests are
likely to be exchanging faster than the NMR time scale. The
plot of chemical shift changes versus SOS concentration for the
SOS methyl proton (Hm) for all three cages is shown in Figure
7, and similar binding isotherms were observed by monitoring
chemical shift changes for methylene SOS protons (Hl) and
pyridyl-He of the Laz ligands within each cage. The chemical
shift change data were fit using HypNMR2008.44 A range of
binding stoichiometries were tested, including 1:1, 1:2, and 1:3
H:G ratios, both with and without a guest self-association
factor (G2). The best fit-to-data model was found for a 1:1
H:G ratio with a dimeric G2 guest association also factored in.
Predicted chemical shift changes for all monitored protons
(Hj/k/m of the guest and He of the host) were an excellent
match to data for all three metal-cryptophanes (Figures S40−
S42). A 1:1 H:G model without consideration of guest self-
association gave a poor fit to data for the chemical shift of the
SOS−OCH2-R proton (Figure S40b). This is notably the
proton environment that displayed chemical shift changes
during the self-titration experiments with SOS. The 1:1
binding constants are listed in Table 1. The binding of the
with chiral self-sorting of Lpy ligands over a 3 month
equilibration period.21
The photoswitching behavior of C1 was studied as an
exemplar for these cages. Photoswitching of C1 in a DMSO
1
solution was monitored by H NMR and ion-mobility mass
spectrometry (IM-MS). UV−vis spectroscopy is typically used
to monitor photoswitching but requires high dilution. Dilution
of a solution of C1 to 30 μM, which is a typical concentration
for UV−vis spectroscopy, resulted in complete disassembly of
the metallo-cryptophane cage (Figure S20). Pd(II)-pyridyl
bonds are relatively labile, and this reversibility means that at
very low concentrations of the cage the backward reactions can
dominate due to Le Chatelier’s principle. This behavior is
consistent with previous reports of a nitrile-appended
palladium metallo-cryptophane in dichloromethane that begins
to disassemble at concentrations below approximately 200 μM
16
1
when monitored by H NMR.
A 600 μM solution of C1 was irradiated with a 355 nm
Nd:YAG laser37 for a total exposure of 1200 s, and a 1H NMR
spectrum acquired. The NMR spectrum of the irradiated
sample is considerably broadened, as was seen for {[Ir-
(C∧N)2]3(Laz-OMe)2}3+,10 which is anticipated if a mixture of
cis and trans isomers is present (Figure S21). However, a new,
sharp peak appears in the spectrum at ∼4.8 ppm, which was
not anticipated. Furthermore, if the solution is switched back
1
to trans-Laz-OMe by exposure to 450 nm light, the H NMR
spectrum of the resultant sample is clearly a mixture of free L1-
OMe and metallo-cryptophane C1, alongside the peak at 4.81
ppm, assigned as a [Pd(en)2]2+ species (Figure S21).
Irradiation of C1 for accumulation times of >1200 s resulted
in the formation of palladium black. Thus, unlike the
{[Ir(C∧N)2]3(Laz)2}3+ cages, {[Pd(en)]3(Laz-OMe)2}6+ is
less robust and undergoes partial disassembly on photo-
isomerization of 3-pyridylazophenyl groups.
IM-MS measures the time taken for a species to diffuse
along a drift tube against the flow of a carrier gas and has
recently found application in supramolecular chemistry.38
Species with a larger radius of diffusion take longer to flow
across the tube; hence, any significant change in size of an
F
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Figure 6. 1H NMR spectra of metallocryptophanes in d6-DMSO. (a) 1D spectra of ligand Laz-OMe (bottom) and C1 (top). (b) 1H−1H NOESY
spectrum of C2.
Chart 1. Guest Species Bound by Cages
however, found for the cage with Laz-OMe, where guest access
into and out of the metallo-cryptophane windows is least
impeded by the side arm chain. The larger [Pd6(Lpy)8]12+ stella
octangula cage bound SOS with a Ka of 1 × 106 M−1 for 1:2
H:G binding.40 A 1:1 H:G complex between SOS and a
curcubit[7]uril-based receptor was reported by Yu and co-
workers with a Ka of 2.4 × 104 M−1.45
1H−1H NOESY NMR spectra were acquired to further
probe the nature of the host−guest interaction. Through-space
couplings were observed for only the [SOS]@C3 system,
possibly as the longer propoxy groups on the C3 cage hinder
guest exchange rates more than would the cages with the
shorter alkoxy groups. Another explanation is that the propoxy
groups themselves occupy space with the metallo-cryptophane
cage, inhibiting guest dynamics within the cage. Given the 1:1
sodium alkyl sulfates by cages C1−C3 is considerably weaker
than for similar systems. There is no obvious correlation
between alkoxide-chain length on the Laz ligand of the cage and
the binding constant. The lowest binding constant was,
G
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naphthalene group, likely due to π−π stacking interactions.47
Guest nap was titrated into 2.75 mM solutions of cages C1−
C3 in d6-DMSO, over a guest concentration range of 0.28−
27.5 mM. In all cases, clear chemical shift changes were
observed for nap, which were different from those seen in self-
titration experiments with nap. The free guest and bound guest
are in exchange, and the nap−CH2CH2NMe2 (Ho) proton was
used to monitor the binding as it showed the largest chemical
shift change without being obscured by peaks from cage or
solvent proton environments. Binding isotherms are shown in
Figure 9. The behavior was not the same for all three cages,
Figure 7. Binding isotherms showing 1H NMR chemical shift changes
in d6-DMSO for SOS methyl proton Hm upon titration into a 3.85
mM solution of metallo-cryptophanes.
Table 1. Binding Constants Obtained for SOS Binding by
Cages C1−C3
C1
C2
C3
KaG2 (M−1
KaHG (M−1
)
)
16.2 1.6
68.6 1.9
5.1 3.3
299.0 9.2
9.1 5.5
115.9 6.9
H:G binding ratio gives a guest occupancy somewhat below
the 55% guest-to-void volume ratio established as ideal by
Rebek and co-workers,46 the latter explanation may be the
most pertinent. Through-space couplings were observed
between the methylene protons on SOS, Hl, and the phenyl
ring of the azo group found on the host architecture, Hf and Hg
(Figure 8), consistent with in-cage binding of the octyl
sulfonate anion and pointing to the formation of CH−π
interactions between the guest and host.
Figure 9. Binding isotherms showing 1H NMR chemical shift changes
in d6-DMSO for nap proton Ho upon titration into a 2.75 mM
solution of metallo-cryptophanes C1−C3.
with cage C1 inducing the greatest chemical shift change.
Furthermore, where the metallo-cryptophane C1 is the host,
the system is in fast exchange on the NMR time scale,
evidenced by the appearance of the nap−CH2CH2NMe2
proton (Ho) as a clear triplet in the high- and low-
Self-titration of nap in d6-DMSO showed small chemical
shift changes, most notably upfield shifts for the protons on the
1
Figure 8. H−1H NOESY spectrum (500 MHz, d6-DMSO) of C3 and SOS. Circled peaks indicate through-space interactions between guest
methylene protons Hl and host arene protons Hf and Hg.
H
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Article
concentration regimes with only a slight broadening at
intermediate concentrations.48 Whereas when C2 or C3 is
the metallo-cryptophane host, the system is exchanging at a
slower rate, approximately in the intermediate exchange region
on the NMR time scale. For these cases, the nap Ho proton is
observed as only a triplet at high concentrations of nap, where
it exists mostly unbound in solution. At lower concentrations,
the signal broadens until at very low concentrations, when
nearly all of nap will be in exchange, the signal broadens to
such a degree it becomes indistinguishable from the baseline
(Figure S50). Hence, the longer ethoxy and propoxy side arms
of the L ligands of C2 and C3, respectively, sterically hinder
access to the internal space of the cage, resulting in a larger
kinetic barrier to encapsulation and de-encapsulation, slowing
the process, which has the effect of broadening the NMR
signals.48 The effect of the size of portals between the exterior
and interior of a cage and the kinetics of host−guest system is
well-documented.49 Attempts to fit the binding isotherms in
Figure 9 to 1:1, 1:2, and 1:3 H:G models were not successful.
As additional evidence for binding, the nap@C1 and nap@C2
systems were further investigated by 1H DOSY NMR. Despite
their significant difference in size, the diffusion constants for
nap and the cages were very similar, indicative of host−guest
binding (Figure S51). The DOSY experiment also confirms
that the metallo-cryptophane cage remains intact in the
presence of nap.
EXPERIMENTAL SECTION
■
Synthesis. H and 13C NMR spectra (including COSY, HSQC,
HMBC, and NOESY spectra) were recorded using a Bruker AV-NEO
11.4 T instrument (500 MHz 1H) with a 5 mm DCH cryoprobe or 5
mm TBO RT-probe and a Bruker 400 MHz NMR spectrometer with
a 5 mm BBFO RT-probe. Diffusion ordered spectroscopy (DOSY)
1
1
measurements were taken using a Jeol ECA 14.1 T (600 MHz H)
spectrometer with a 5 mm ROYAL probe. The pulse sequences used a
bipolar pulse pair simulated echo (BPPSTE). High-resolution
electrospray mass spectra (ESI-MS) were recorded on a Bruker
micro-TOF-Q mass spectrometer. IM-MS was performed on a Synapt
G2-Si Imaging Mass Spectrometer.
( )-2,7,12-Tripropoxy-3,8,13-trimethoxy-10,15-dihydro-5H-
tribenzo[a,d,g]cyclononatriene (pCTG),22 3-(4-benzoyl chlorideazo)-
pyridine,10 and ( )-2,7,12-trimethoxy-3,8,13-tris(3-pyridyl-4-azophe-
nylcarboxy)-10,15-dihydro-5H-tribenzo[a,d,g]cyclononatriene (Laz-
OMe)10 were synthesized according to previously published
procedures. A new route to 2,7,12-triethoxy-3,8,13-trimethoxy-
10,15-dihydro-5H-tribenzo[a,d,g]cyclononatriene (eCTG)26 was em-
ployed via ( )-2,7,12-triethoxy-3,8,13-tris(propenyloxy)-10,15-dihy-
dro-5H-tribenzo[a,d,g]cyclononatriene, the latter synthesized by
literature procedures.50 Detailed 13C{1H} NMR assignments of Laz-
OEt and Laz-OPr are given in the Supporting Information.
( )-2,7,12-Triethoxy-3,8,13-trihydroxy-10,15-dihydro-5H-
tribenzo[a,d,g]cyclononatriene (eCTG). ( )-2,7,12-Triethoxy-
3,8,13-tris(propenyloxy)-10,15-dihydro-5H-tribenzo[a,d,g]-
cyclononatriene (1.90 g, 3.36 mmol) and triphenylphosphine (0.26 g,
1.01 mmol) were dissolved in a mixture of diethylamine (15 mL),
water (15 mL), and anhydrous THF (80 mL) under an atmosphere of
N2. The solution was heated to reflux, and palladium(II) acetate (0.04
g, 0.17 mmol) was added in one portion. The solution was heated
overnight, and the resultant black suspension was filtered through
Celite to yield an orange solution. The solvent was removed, and the
residue was triturated in ethanol. The product was filtered and washed
with ethanol and then diethyl ether to yield the product as an off-
white powder (1.03 g, 2.29 mmol, 68%). 1H NMR (300 MHz,
CDCl3): δ 6.86 (s, 3H, ArH), 6.78 (s, 3H, ArH), 5.44 (bs, 3H, OH),
4.69 (d, 3H, J = 13.7 Hz, −CHaxH−), 4.08 (q, 6H, J = 7.0 Hz,
-OCH2CH3), 3.47 (d, 3H, J = 13.8 Hz, −CHeqH−), 1.40 (t, 9H, J =
7.0 Hz, -OCH2CH3). 13C{1H} NMR (75 MHz, CDCl3): δ 143.5,
143.2, 131.4, 130.2, 114.3, 112.2, 63.6, 35.2, 13.8. ESI-MS (+ve) [M +
Na]+: m/z 473.1936, calcd m/z 473.1940. Data consistent with the
literature.26
( )-2,7,12-Triethoxy-3,8,13-tris(3-pyridyl-4-azophenylcarboxy)-
10,15-dihydro-5H-tribenzo[a,d,g]cyclononatriene (Laz-OEt). eCTG
(219 mg, 0.49 mmol) was dissolved in anhydrous THF (60 mL)
under N2; anhydrous triethylamine (6 mL) was added, and the
mixture was stirred for 30 min. The solution was transferred to a flask
containing 3-(4-benzoyl chlorideazo)pyridine (738 mg, 2.96 mmol)
and stirred at room temperature for 3 days. The suspension was
filtered, and the eluent was collected. The solvent was removed to
yield an orange residue that was triturated in methanol (200 mL),
filtered, and washed with methanol and diethyl ether to yield the
CONCLUSIONS
■
Tripodal cavitand ligands based on a tribenzo[a,d,g]-
cyclononene scaffold with appended 3-pyridyl-azo-phenyl
groups can self-assemble with a cis-protected Pd(II) species
to form trigonal bipyramidal {[Pd(en)]3(Laz)2}6+ cages of the
metallo-cryptophane family but disassemble at low concen-
trations. Unlike some previously reported metallo-crypto-
phanes, ethylenediamine is a suitable cis-protecting chelate
ligand for these cages and M3L2 to M6L8 cage rearrangement
does not occur. The ligands themselves all exhibit the
reversible trans → cis photoisomerization that is typical of
azoheteroarene species. However, there is no evidence that the
{[Pd(en)]3(Laz)2}6+ cages can be photoisomerized while
maintaining their cagelike structure. A solution of {[Pd-
(en)]3(Laz-OMe2)}6+ shows spectral changes upon exposure to
first 355 nm light and then 450 nm light but is accompanied by
clear evidence of a significant degree of dissociation of the
cage. This behavior is in direct contrast to that of the
previously studied {[Ir(C∧N)2]3(Laz-OMe)2}3+ cages, where
spectral data indicated reversible photoswitching and no
compositional change to the cage in its cis-rich form. The
higher level of robustness of the Ir(III) cages compared with
the Pd(II) cages is likely to be a consequence of the higher
degree of lability of Pd(II). This suggests that the use of inert
metals, while significantly slowing self-assembly processes, is a
useful tool for the synthesis of shape-changing metallocages.
All three {[Pd(en)]3(Laz)2}6+ metallo-cryptophanes behaved
as nanoscale host assemblies in DMSO solutions and were
shown to bind disparate guests, namely, an anionic surfactant,
sodium octyl sulfate, and naphthalimide derivative N-[2-
(dimethylamino)ethyl]-1,8-naphthalimide. Subtle differences
in the binding behavior of the three cage hosts may be due to a
degree of self-binding in which the longer alkyl chains of Laz-
OPr in particular are able to restrict guest access to the cage
portals or themselves occupy space within the hydrophobic
cage interior.
1
product as a bright orange powder (323 mg, 0.30 mmol, 61%). H
NMR (500 MHz, CDCl3): δ 9.25 (s, 3H, He), 8.75 (d, 3H, J = 4.4 Hz,
Hb), 8.36 (d, 6H, J = 6.8 Hz, Hg), 8.18 (d, 3H, J = 8.0 Hz, Hd), 8.04
(d, 6H, J = 8.0 Hz, Hf), 7.47 (m, 3H, Hc), 7.20 (s, 3H, Hi), 6.99 (s,
3H, Hh), 4.83 (d, 3H, J = 13.6 Hz, −CHaxH−), 4.07 (q, 6H, J = 6.8
Hz, -OCH2CH3), 3.68 (d, 3H, J = 13.6 Hz, −CHeqH−), 1.26 (t, 9H, J
= 6.8 Hz, -OCH2CH3). 13C{1H} NMR (125 MHz, CDCl3): δ 164.2,
155.2, 152.5, 149.3, 147.9, 147.8, 139.2, 138.2, 132.1, 131.8, 131.5,
127.2, 124.2, 124.1, 123.1, 115.8, 65.0, 36.7, 14.9. ESI-MS (+ve) [M +
H]+: m/z 1078.3662, calcd m/z 1078.3883.
( )-2,7,12-Tripropoxy-3,8,13-tris(3-pyridyl-4-azophenylcarboxy)-
10,15-dihydro-5H-tribenzo[a,d,g]cyclononatriene (Laz-OPr). pCTG
(118 mg, 0.24 mmol) was dissolved in anhydrous THF (30 mL)
under N2; anhydrous triethylamine (3 mL) was added, and the
mixture was stirred for 30 min. The solution was transferred to a flask
containing 3-(4-benzoyl chlorideazo)pyridine (363 mg, 1.48 mmol)
and stirred at room temperature for 3 days. The suspension was
I
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Article
filtered, and the eluent was collected. The solvent was removed to
yield an orange residue that was triturated in methanol (100 mL),
filtered, and washed with methanol and diethyl ether to yield the
Full reaction schemes, NMR spectra, UV−vis spectra,
mass spectra, fitting of NMR binding data, crystallo-
graphic tables, and additional crystal structures (PDF)
1
product as a bright orange powder (154 mg, 0.14 mmol, 57%). H
NMR (500 MHz, CDCl3): δ 9.25 (s, 3H, He), 8.75 (d, 3H, J = 1.5, 4.8
Hz, Hb), 8.36 (d, 6H, J = 9.0 Hz, Hg), 8.19 (dt, 3H, J = 1.5, 8.1 Hz,
Hd), 8.04 (d, 6H, J = 8.7 Hz, Hf), 7.48 (dd, 3H, J = 4.8, 8.1 Hz, Hc),
7.21 (s, 3H, Hi), 6.98 (s, 3H, Hh), 4.85 (d, 3H, J = 15.0 Hz,
−CHaxH−), 3.97 (m, 6H, -OCH2CH2CH3), 3.69 (d, 3H, J = 13.8 Hz,
−CHeqH−), 1.68 (sextet, 6H, J = 7.2 Hz, -OCH2CH2CH3), 0.88 (t,
9H, J = 7.2 Hz, -OCH2CH2CH3). 13C NMR (126 MHz, CDCl3): δ
164.2, 155.2, 152.6, 149.4, 147.9, 147.7, 139.1, 138.2, 132.1, 131.6,
131.5, 127.1, 124.2, 124.0, 123.1, 115.6, 70.7, 36.7, 22.6, 10.5. ESI-MS
(+ve) [M + H]+: m/z 1120.4137, calcd m/z 1120.4352.
Accession Codes
CCDC 2079170−2079171 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
General Procedure for Cage Assembly. The appropriate Laz
(4.0 mg) was dissolved in d6-DMSO (0.3 mL). Pd(en)(NO3)2 (1.5
equiv) was dissolved in d6-DMSO (0.3 mL) and added dropwise to
the solution of Laz. The bright orange solution was left to stand for 5
Michaele J. Hardie − School of Chemistry, University of Leeds,
Leeds LS2 9JT, U.K.; orcid.org/0000-0001-6586-7981;
Email: m.j.hardie@leeds.ac.uk
1
min after which time a H NMR spectrum was acquired.
{[Pd(en)]3(Laz-OMe)2}·6(NO3) (C1). 1H NMR (500 MHz, d6-
DMSO): δ 9.62 (d, 6H, J = 13.3 Hz, He), 9.15 (bs, 6H, Hb), 8.52
(bs, 6H, Hd), 8.37 (d, 12H, J = 8.5 Hz, Hg), 8.11 (t, 12H, J = 8.3 Hz,
Hf), 7.95 (t, 6H, J = 8.1 Hz, Hc), 7.60 (s, 6H, Hi), 7.35 (s, 6H, Hh),
5.67 (bs, 15H, NH), 4.93 (d, 6H, J = 14.1 Hz, −CHaxH−), 3.75 (s,
24H, OCH3/−CHeqH−), 2.69 (bs, 12H, Ha). ESI-MS (+ve):
{[Pd(en)]3(Laz-OMe)2}6+ m/z 428.1710, calcd m/z 428.4311.
{[Pd(en)]3(Laz-OEt)2}·6(NO3) (C2). 1H NMR (500 MHz, d6-
DMSO): δ 9.62 (m, 6H, He), 9.15 (m, 6H, Hb), 8.51 (bs, 6H, Hd),
8.37 (t, 12H, J = 8.3 Hz, Hg), 8.10 (t, 12H, J = 8.3 Hz, Hf), 7.94 (t,
6H, J = 8.1 Hz, Hc), 7.56 (bs, 6H, Hi), 7.34 (bs, 6H, Hh), 5.67 (bs,
12H, NH), 4.87 (bs, 6H, −CHaxH−), 4.04 (bs, 12H, OCH2CH3),
3.71 (bs, 6H, −CHeqH−), 2.70 (bs, 12H, Ha), 1.16 (m, 18H,
OCH2CH3).
Authors
Edward Britton − School of Chemistry, University of Leeds,
Leeds LS2 9JT, U.K.
Richard J. Ansell − School of Chemistry, University of Leeds,
Leeds LS2 9JT, U.K.
Mark J. Howard − School of Chemistry, University of Leeds,
Leeds LS2 9JT, U.K.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.1c01297
Notes
The authors declare no competing financial interest.
Data accessibility: data supporting this study are available at
https://doi.org/10.5518/1025.
{[Pd(en)]3(Laz-OPr)2}·6(NO3) (C3). 1H NMR (500 MHz, d6-
DMSO): δ 9.60 (m, 6H, He), 9.16 (m, 6H, Hb), 8.50 (bs, 6H, Hd),
8.35 (t, 12H, J = 8.6 Hz, Hg), 8.11 (t, 12H, J = 8.2 Hz, Hf), 7.95 (t,
6H, J = 8.0 Hz, Hc), 7.56 (bs, 6H, Hi), 7.35 (bs, 6H, Hh), 5.67 (bs,
12H, NH), 4.90 (bs, 6H, −CHaxH−), 3.95 (bs, 12H,
OCH2CH2CH3), 3.72 (bs, 6H, −CHeqH−), 2.70 (bs, 12H, Ha),
1.53 (bs, 12H, OCH2CH2CH3), 0.79 (m, 18H, OCH2CH2CH3).
ACKNOWLEDGMENTS
■
The authors thank the EPSRC for a studentship (1799710) for
E.B. This work was carried out with support of the Diamond
Light Source (MT-20570). The authors acknowledge the
support of the Henry Royce Institute for E.B. through the
Royce PhD Equipment Access Scheme enabling access to soft
ionization and imaging mass spectrometry facilities at Royce@
Liverpool (EPSRC Grant EP/R00661X/1). The authors thank
Dwayne Heard’s research group for access and assistance with
the YAG laser, Christopher M. Pask for assistance with
collection of X-ray data, and Matthew Snelgrove for assistance.
1
Host−Guest Studies. All H NMR titrations were performed at
300 K using the following procedure, given in detail for C1 and SOS.
A stock solution of C1 was prepared in d6-DMSO (3.85 mM, 2 mL);
0.55 mL of the stock was transferred to an NMR tube, and an initial
1H NMR spectrum was acquired. SOS (19.7 mg, 84.8 μmol) was
dissolved in 1 mL of the stock solution of C1. Aliquots of the solution
containing SOS were added to the NMR tube incrementally such that
the H:G ratio varied between 1:0.1 and 1:10. At each interval, the
NMR tube was mixed with a vortex mixer and equilibrated for 5 min
1
before the H NMR spectrum was recorded. Binding isotherms were
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ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.1c01297.
J
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