Capsule formation in novel cadmium cluster metallocavitands

Article abstract of DOI:10.1039/b710809e

We report the synthesis and characterization of a new heptanuclear cadmium cluster complex formed within a Schiff base macrocycle and study its surprising dimerization in the solid-state and solution to form capsules. The Royal Society of Chemistry.

Full text of DOI:10.1039/b710809e

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Capsule formation in novel cadmium cluster metallocavitands{
Peter D. Frischmann and Mark J. MacLachlan*
Received (in Austin, TX, USA) 24th July 2007, Accepted 17th August 2007
First published as an Advance Article on the web 28th August 2007
DOI: 10.1039/b710809e
We report the synthesis and characterization of a new
heptanuclear cadmium cluster complex formed within a
Schiff base macrocycle and study its surprising dimerization
in the solid-state and solution to form capsules.
The self-assembly of cavitands is an important concept within
supramolecular chemistry.1 Capsules formed by bowl-shaped
organic macrocycles, such as calixarenes and resorcinarenes, are
attractive as nano-reaction chambers, where they can facilitate
reactions that occur by a different pathway than in the bulk.2 The
geometry and chemistry of the cavity is important for directing the
Scheme 1 Reaction of macrocycles 1a–b with seven equivalents of
size- and shape-selective processes. Homodimerization of cavitands
Cd(OAc)2 in EtOH affords metallocavitands 2a–b (a R = C2H5, b R =
into capsules is most often facilitated by H-bonding3 or metal
C8H17). The seventh Cd ion and sixth acetate ligand are obscured by the
coordination, where the transition metals act as coordinative
depiction of the cluster.
fasteners, covalently sealing two cavitands.4 The quintessential
bowl-like structure of the latter cavitands results from the organic
macrocycle and not the presence of transition metals.
Metallocavitands in which metals are intrinsic structural elements
of the cavity are rare due to often unpredictable coordination
geometry but should exhibit rich host–guest chemistry much like
their organic analogues.5 The design of self-assembling inorganic
cavitands with multiple metal sites accessible to encapsulated
guests promises to wed the selectivity and recognition of organic
supramolecular chemistry with the catalytic, magnetic, and optical
properties of metals, producing functional materials.6
resonance displayed an ABX2 coupling pattern arising from
diastereotopic protons, indicative of C3v symmetry. Cadmium
3
satellites with JCd–H = 34.2 Hz were observed for the imine
resonances, confirming that the N2O2 pockets of the macrocycle
were occupied by cadmium.10 In order to determine the structure
of the cadmium complexes, we undertook a single-crystal X-ray
diffraction study of 2a.{ Crystals of 2a were grown from DMF,
and its solid-state molecular structure is illustrated in Fig. 1.
While zinc carboxylate clusters are well known (e.g., basic zinc
acetate [Zn4O(OAc)6]), cadmium carboxylate cluster complexes are
less common, but are of interest as fluorescent materials11 and
molecular building blocks for metal–organic frameworks.12 In 2a,
the macrocycle coordinates three Cd2+ ions in the N2O2 salphen-
like pockets, a rare binding motif for cadmium. Similar to previous
reports,11b,13 the Cd–N and Cd–O bond lengths are 2.307(9) and
We recently reported that the reaction of macrocycle 1a with
zinc acetate forms a heptanuclear zinc cluster complex, 3a.7 In this
structure, the metallomacrocycle adopts a bowl shape, accom-
modating a basic zinc acetate cluster at its apex. Herein, we report
on the formation of a novel cadmium acetate cluster complex of
macrocycle 1, with an even deeper bowl shape. Although the
cadmium cluster also has seven metal centers, it is structurally
distinct from the zinc cluster complex. Moreover, we demonstrate
for the first time that these metallocavitands form interlocking
capsules in the solid state and reversibly dimerize in aromatic
solvents and DMF. This self-assembly process appears to be
entropy-driven, reminiscent of Cram’s velcrands.8
Reacting macrocycles 1a and 1b9 with Cd(OAc)2 afforded red
microcrystalline solids 2a and 2b (Scheme 1). Compound 2a is only
soluble in DMF, while 2b is soluble in various organic solvents. 1H
NMR spectroscopy of the products (hot DMF-d7 for 2a, CDCl3
for 2b) showed that they retained the three-fold symmetry of the
starting macrocycle and contained acetate ligands. The OCH2
˚
2.240(6) A, respectively. This sterically strained coordination
distorts the near-planar macrocycle into a bowl shape that further
coordinates a [Cd3O(OAc)6Cd(H2O)3] cluster. Above the macro-
cycle, each of the catechol moieties is coordinated to a Cd2+ ion,
and these three cadmium ions are bridged by a central oxo ligand.
Interestingly, this trigonal pyramidal oxo ligand is coordinated to
only three Cd2+ ions, whereas in the zinc complexes, the oxo ligand
is tetrahedral. Bridging acetate ligands hold the capping octahedral
Cd(OH2)32+ species in place. The solid-state structure is consistent
with the solution NMR spectroscopic data. Remarkably, complex
2a is stable in boiling water for hours despite the known hydrolytic
instability of Schiff bases and the lability of Cd–OAc bonds.
The first evidence for dimerization of 2a came from its solid-
state structure – in the crystal structure, the molecule is packed into
perfect capsules with crystallographically-imposed D3d symmetry
(Fig. 1(c) and (d)). The complementary monomers organize in a
face-to-face interlocking fashion with a 60u rotation between them.
Department of Chemistry, University of British Columbia, 2036 Main
Mall, Vancouver, BC, V6T 1Z1, Canada.
E-mail: mmaclach@chem.ubc.ca; Fax: 604-822-2847; Tel: 604-822-3070
{ Electronic supplementary information (ESI) available: Synthetic proce-
dures, NMR data and crystallographic parameters. See DOI: 10.1039/
b710809e
…
˚
The capsule is stabilized by 12 weak CH p interactions (3.00 A)
as illustrated in Fig. 1(e). A single DMF molecule appears to be
4480 | Chem. Commun., 2007, 4480–4482
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Fig. 2 (a) Variable-temperature 400 MHz 1H NMR spectra of 2a in
DMF-d7 ([2a] = 5 mmol L21). Protons are labeled according to Scheme 1
with the primes referring to dimeric species and an asterisk indicating
solvent. (b) Van’t Hoff plot of 2a in DMF-d7 ([2a] = 2.6 mmol L21) from
integration of resonances assigned to protons Ha and Hc (Scheme 1) in the
1H NMR spectra at 238, 247, 256 and 265 K.
1
protons Ha and Hc in the H NMR spectrum). An enthalpy of
19 ¡ 1 kJ mol21 and entropy of 110 ¡ 2 J mol21 K21 for
dimerization was calculated from the van’t Hoff plot.
Unexpectedly, these thermodynamic parameters indicate that
dimerization in DMF is an entropy-driven process.
In an effort to expand our thermodynamic study to other
solvents, our focus shifted to metallocavitand 2b. Significant
broadening of the imine, aromatic and OCH2 resonances was
observed by 1H NMR spectroscopy in benzene-d6, toluene-d8 and
p-xylene-d10 (but not CDCl3). This preliminary evidence for
dimerization prompted us to undertake VTVC 1H NMR
experiments. In these solvents, it was not possible to resolve
distinct monomer and dimer resonances, and guests could not be
observed directly due to rapid exchange. However, the variation of
the imine chemical shift as a function of concentration was fit to a
dimerization model, enabling us to extract the association
constants at each temperature.15 Thermodynamic parameters for
self-association were then determined from van’t Hoff plots. The
experimental association constants, enthalpies, and entropies of
dimerization for compound 2b are shown in Table 1.
Fig. 1 Solid-state depictions of 2a as determined by single-crystal X-ray
¯
diffraction (crystallized from DMF, R3m space group). (a) Side view of the
metallocavitand. (b) Expanded view of the capping cadmium cluster
(periphery omitted). (c) Top view of the dimeric capsule. (d) Side view of
…
the capsule. (e) Expanded view of the intermolecular CH p interactions
between Hc protons (Scheme 1) and the p cloud of the complementary
monomer moiety (contacts between H7 and C5 are depicted; see CCDC
643623). Hydrogen atoms are omitted for clarity in (a) through (d). Most
H atoms and some C, O, and N atoms are omitted for clarity in (e) (grey =
C, blue = N, red = O, yellow = Cd).
encapsulated in the interior of the complex, but its position could
not be accurately determined due to disorder.
The association constants for dimerization (Kdim) of 2b in the
three aromatic solvents are similar in magnitude. Surprisingly, in
p-bonding solvents dimerization of these cluster-capped macro-
cycles appears to be an entropy-driven process. Most self-
association processes are enthalpy-driven and entropy-opposed since
order is generally being imparted on the system and the dimers are
held together by strong intermolecular interactions.
Much like Cram’s velcrands and Rebek’s molecular capsules,16
we attribute the entropy-driven process to the expulsion of solvent
molecules from monomers upon dimerization. Although entropy-
driven aggregation is common in aqueous media where it is
important in biological systems (hydrophobic effect), it is rarely
observed in non-polar organic solvents. In the case of 2a and 2b,
aromatic solvents can form strong p–p interactions with the
interior of the bowl of the monomeric metallocavitand. When
dimerization of the metallocavitand occurs, solvent is expelled
from the bowl, increasing the net entropy in the system.
To probe the dimerization of compound 2a in solution, we
carried out variable temperature, variable concentration (VTVC)
1H NMR experiments. At room temperature, the resonances of 2a
in DMF-d7 are broad but they sharpen upon heating. When a
sample of 2a in DMF-d7 was cooled to 265 K the resonances
characteristic of the complex split into two sets of peaks (Fig. 2(a)).
As the intensity of the peaks showed concentration dependence, we
were able to assign one set of resonances to the monomer, and the
other to the dimer. Significantly, in the dimer, the aromatic
resonances assigned to the protons on the catechol ring (Hc from
Scheme 1) were observed at 5.8 ppm, more than 0.8 ppm upfield
from the same resonance assigned to the monomeric complex. This
additional shielding is consistent with formation of a face-to-face
dimer, as the protons on the catechol ring are directly over the
p-cloud of the diimine rings of the complementary complex as
shown in Fig. 1(e).14
Fig. 2(b) displays the van’t Hoff plot constructed to establish the
thermodynamics of dimerization of metallocavitand 2a in DMF-
d7. Association constants at 238, 247, 256 and 265 K were obtained
from integration of the monomer and dimer resonances (aromatic
While the entropy changes upon dimerization are consistently
positive, there are no clear trends for the enthalpy changes.
The balance between solvent–solvent, macrocycle–solvent, and
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Table 1 Thermodynamic parameters for dimerization of 2b and 3b (R = C8H17) in different solvents compared to 2a (R = C2H5) in DMF-d7
Complex
Solventa
Kdim (25 uC)b/L mol21
DH/kJ mol21
DS/J mol21 K21
2a
2b
DMF-d7
270 ¡ 10
800 ¡ 100
1500 ¡ 400
1000 ¡ 300
10 ¡ 3
19 ¡ 1
27 ¡ 5
1 ¡ 4
11 ¡ 8
24 ¡ 12
110 ¡ 2
32 ¡ 14
64 ¡ 14
94 ¡ 24
100 ¡ 34
Benzene-d6
Toluene-d8
p-Xylene-d10
Benzene-d6
3b
a
Solubility and the melting/boiling point of the solvents limited the temperature ranges over which the experiments could be performed.
Association constants at 25 uC are calculated from van’t Hoff plots.
b
B. C. Gibb and V. Ramamurthy, J. Am. Chem. Soc., 2004, 126, 14366;
macrocycle–macrocycle interactions leads to near cancellation of
the enthalpy changes that occur upon dimerization.
(c) J. Chen and J. Rebek, Jr., Org. Lett., 2002, 4, 327; (d) J. Kang,
J. Santamaria, G. Hilmersson and J. Rebek, Jr., J. Am. Chem. Soc.,
1998, 120, 7389.
3 For a review, see: (a) L. J. Prins, D. N. Reinhoudt and P. Timmerman,
Angew. Chem., Int. Ed., 2001, 40, 2382. Not included in the review: (b)
I. Vatsouro, V. Rudzevich and V. Bo¨hmer, Org. Lett., 2007, 9, 1375; (c)
M. Yamanaka, K. Ishii, Y. Yamada and K. Kobayashi, J. Org. Chem.,
2006, 71, 8800; (d) A. Bogdan, Y. Rudzevich, M. O. Vysotsky and
V. Bo¨hmer, Chem. Commun., 2006, 2941; (e) T. Amaya and J. Rebek,
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4 (a) N. P. Power, S. J. Dalgarno and J. L. Atwood, New J. Chem., 2007,
31, 17; (b) C. J. Sumby, J. Fisher, T. J. Prior and M. J. Hardie, Chem.–
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A. Decken and F.-G. Fontaine, Angew. Chem., Int. Ed., 2007, 46, 4979;
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7 (a) A. J. Gallant, J. H. Chong and M. J. MacLachlan, Inorg. Chem.,
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Compared with the macrocyclic bowls of the zinc cluster
complexes, the bowls of 2a and 2b are deeper and greater in
volume. This is a consequence of accommodating the larger
cadmium cluster inside the macrocycle, requiring the ring to open
wider. To determine whether the bowl dimensions influence the
dimerization of the complexes, we synthesized zinc complex 3b and
measured its dimerization constants in benzene-d6 using VTVC 1H
NMR spectroscopy. Remarkably, at 298 K the association
constant for the zinc bowl complex 3b is only 10 ¡ 3 mol L21
,
substantially smaller than that of cadmium complex 2b. The zinc
cluster complex also exhibits entropy-driven dimerization. Unlike
organic capsule-forming molecules, which often require several
steps to modify, our results illustrate a simple method to modify
the bowl shape of the metallocavitands, and thus significantly alter
the monomer–dimer equilibrium.
In summary, we have discovered a new stable heptanuclear
cadmium cluster complex that is formed within a Schiff base
macrocycle. A single-crystal X-ray diffraction experiment revealed
that these molecules organize into face-to-face capsules in the solid
state. We have demonstrated the first reversible dimerization of
these metallocavitands, a process that appears to be entropy-driven.
Moreover, we have illustrated the ability to use coordination
chemistry to change the curvature of the bowl, and to modify the
thermodynamics of capsule formation. These tunable metalloca-
vitand capsules with accessible metal sites on their interiors are
alluring candidates for host–guest catalysis and molecular
recognition. We are now expanding the dimerization and guest
inclusion studies of the metallocavitands.
9 A. J. Gallant, J. K.-H. Hui, F. E. Zahariev, Y. A. Wang and
M. J. MacLachlan, J. Org. Chem., 2005, 70, 7936.
We thank Amanda Gallant who carried out some of the initial
experiments, and Jonathan Chong and Brian Patrick for assistance
solving the structure of 2a. We thank NSERC for funding this
research.
10 We have conducted 113Cd NMR on an analogous hexyloxy substituted
metallocavitand and observed three distinct resonances at 139.5 (t,
3JCd–H = 34.2), 10.1 and 1.1 ppm, consistent with the three cadmium
environments in the crystal structure of 2a (CDCl3, 84.86 MHz;
calibrated to 0 ppm with a 0.1 mol L21 solution of Cd(ClO4)2 in D2O).
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Notes and references
{ Crystal data for 2a: C87H121Cd7N13O35, Mr = 2695.77, red plate (0.25 6
¯
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26.128(3) s, V = 18654(4) s3, Z = 6, Dc = 1.440 g cm23, l = 0.710 69 s,
T = 173(2) K, , 46300 reflections collected, 2884 unique (Rint = 0.1841).
Final GoF = 1.005, R1 = 0.0665, wR2 = 0.1847, R indices based on 1816
reflections with I . 2s(I). CCDC 643623. For crystallographic data in CIF
or other electronic format see DOI: 10.1039/b710809e
14 Preliminary attempts to observe guests in DMF-d7 by 1H NMR
spectroscopy have been hindered due to solubility constraints at low
temperature (DMF-d7 is the only solvent in which monomer and dimer
peaks of 2a may be resolved).
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4482 | Chem. Commun., 2007, 4480–4482
This journal is ß The Royal Society of Chemistry 2007