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10.1021/ar020254k CCC: $25.00 2003 American Chemical Society VOL. 36, NO. 8, 2003 / ACCOUNTS OF CHEMICAL RESEARCH 621
Published on Web 05/23/2003
Cucurbituril Homologues and Derivatives Lee et al.
FIGURE 1. X-ray crystal structures of CB[n] (n ) 5-8). Color codes: carbon, gray; nitrogen, blue; oxygen, red.
622 ACCOUNTS OF CHEMICAL RESEARCH / VOL. 36, NO. 8, 2003
Cucurbituril Homologues and Derivatives Lee et al.
Chart 1 strain energy 1 kcal/mol. CB[5] and CB[8] have less than
6 kcal/mol relative strain energy, while this is significantly
high for other homologues. These results nicely cor-
roborate the experimental composition of the homologue
mixture and may explain why only a trace amount of CB-
[n] for n higher than 8 is observed.
Chart 2
Scheme 3
FIGURE 6. X-ray crystal structure of [Cu(cyclen)(H2O)] encapsulated in CB[8]: (a) space-filling model and (b) ball-and-stick model. Color
code: copper, green; oxygen, red; nitrogen, blue; carbon, gray.
VOL. 36, NO. 8, 2003 / ACCOUNTS OF CHEMICAL RESEARCH 625
Cucurbituril Homologues and Derivatives Lee et al.
Scheme 4
9). The portal and cavity sizes of CB*[5] and CB*[6] are
essentially the same as those of the CB counterparts. Both
CB*[5] and CB*[6] are soluble in common solvents such
as water, methanol, DMF, and DMSO. Interestingly, both
are more soluble in water (2 10-1 M) than in organic
FIGURE 10. Responses of an ISE based on CB*[6] to acetylcholine
solvents (3 10-2 M or less). The origin of their high
(Ach+) and other interfering ions including choline (Ch+).
solubility in water is not clearly understood.
FT mass spectrometry.43 The trapped gas molecules fail The remarkable solubility in water at a neutral pH
to escape as the portals are capped with ammonium ions. allowed us to study their host-guest chemistry in neutral
If an ionophore such as 18-crown-6 is present in the gas water. In neutral water, CB*[6] forms a stable 1:1 host-
phase, the ammonium ion lid can be removed, and the guest complex with acetylcholine, an important neu-
guest gets released. The rate of guest release depends on rotransmitter, whereas choline shows little interaction
its size. Recently, Miyahara and co-workers reported the with CB*[6]. CB*[6] therefore behaves as an artificial
synthesis of ammonium ion lid free Me10CB[5], and its receptor that can differentiate acetylcholine from choline
gas absorption and desorption properties.44 Gases of small in neutral water, which may find useful applications in
(such as He, Ne, and H2) or large diameters (such as Kr, neuroscience. Metal ion binding to CB*[5] has been also
Xe, and CH4) compared to the portal size are not absorbed studied in neutral water. The good solubility of CB*[n] in
significantly. However, gases of intermediate sizes (N2, O2, organic solvents allows fabrication of membrane elec-
Ar, N2O, NO, CO, and CO2) are absorbed and released in trodes for ion sensing. The membrane electrode prepared
cycles indicating the possible use of Me10CB[5] in the solid from CB*[6] detects acetylcholine with high selectivity over
state as a molecular sieve. choline and other interfering ions such as Na+, K+, and
4.2. Soluble Cucurbiturils (CB*[n]). Most CB homo- NH4+ (Figure 10). The membrane electrode made with
logues and Me10CB[5] are practically insoluble in common CB*[5] behaves as an ion selective electrode for Pb2+.
solvents limiting their use. Recently we succeeded in Recently, Nakamura and co-workers46 reported the first
synthesizing new soluble CB[n] derivatives, CB*[n] (n ) unsymmetrically substituted cucurbituril, diphenylcucurbit-
5, 6), by the reaction of cyclohexanoglycoluril and form- [6]uril, (Ph2CB[6]). Reaction of a mixture of diphenylgly-
aldehyde (Scheme 6).45 The NMR data revealed cyclic coluril and glycoluril (1:5) with formaldehyde produced a
pentamer and hexamer as major products in a 8:1 ratio, mixture of CB[6] and Ph2CB[6] from which Ph2CB[6] was
with a small amount of unidentified homologues. After a isolated in 30% yield by gel permeation chromatography
series of dissolutions and fractional crystallizations, CB*- (Scheme 7). Comprehensive structural characterization of
[5] and CB*[6] were isolated in 16% and 2% yields, Ph2CB[6] was provided by NMR studies of its soluble
respectively. Their X-ray analyses revealed the expected spermine complex. The synthesis of Ph2CB[6] may be a
structures with cyclohexane rings outside decorating the route for further functionalization of the macrocycle via
equators reminiscent of the ringed planet Saturn (Figure the phenyl rings.
628 ACCOUNTS OF CHEMICAL RESEARCH / VOL. 36, NO. 8, 2003
Cucurbituril Homologues and Derivatives Lee et al.
5. Summary and Perspectives (4) Whang, D.; Jeon, Y.-M.; Heo, J.; Kim, K. Self-Assembly of a
Polyrotaxane Containing a Cyclic Bead in Every Structural Unit
In this Account we covered the new cucurbituril homo- in the Solid State. J. Am. Chem. Soc. 1996, 118, 11333-11334.
(5) Whang, D.; Kim, K. Polycatenated Two-Dimensional Polyrotaxane
logues and derivatives with specific reference to their Net. J. Am. Chem. Soc. 1997, 119, 451-452.
synthesis, host-guest chemistry, and application pros- (6) Lee, E.; Heo J.; Kim, K. A Three-Dimensional Polyrotaxane
pects. A subtle interplay between the homologues of Network. Angew. Chem., Int. Ed. 2000, 39, 2699-2701.
(7) Park, K.-M.; Whang, D.; Lee, E.; Heo, J.; Kim, K. Transition Metal
varying cavity dimensions and the size and nature of the Ion Directed Supramolecular Assembly of One- and Two-
guests has resulted in a broad spectrum of new host- Dimensional Polyrotaxanes Incorporating Cucurbituril. Chem. Eur.
guest systems. The diversity in guest binding behavior has J. 2002, 8, 498-508.
(8) Whang, D.; Park, K.-M.; Heo, J.; Ashton, P.; Kim, K. Molecular
led to several interesting studies such as redox control of Necklace: Quantitative Self-Assembly of a Cyclic Oligorotaxane
guest binding, stabilization of charge-transfer complexes from Nine Molecules. J. Am. Chem. Soc. 1998, 120, 4899-4900.
inside the host cavity, encapsulation of drug molecules, (9) Roh, S.-G.; Park, K.-M.; Sakamoto, S.; Tamaguchi, K.; Kim, K.
Synthesis of a Five-Membered Molecular Necklace. Angew.
formation of redox-controllable vesicles, and so on. On Chem., Int. Ed. 1999, 38, 637-641.
the basis of these recent studies, numerous applications (10) Park, K.-M.; Kim, S.-Y.; Heo, J.; Whang, D.; Sakamoto, S.;
in broad disciplines can be envisaged including separa- Yamaguchi, K.; Kim, K. Designed Self-Assembly of Molecular
Necklaces. J. Am. Chem. Soc. 2002, 124, 2140-2147.
tion, transport, sensor, catalysis, drug/gene delivery, and (11) Lee, J. W.; Ko, Y. H.; Park, S.-H.; Yamaguchi, K.; Kim, K. Novel
controlled drug release. The field of CB-based functional Pseudorotaxane-Terminated Dendrimers. Angew. Chem., Int. Ed.
2001, 40, 746-749.
materials and devices is also only in its infancy and
(12) Jun, S. I.; Lee, J. W.; Sakamoto, S.; Yamaguchi, K.; Kim, K.
prospects are enormous. In particular, CB-based molec- Rotaxane-Based Molecular Switch with Fluorescence Signaling.
ular switches, memories, and machines may be developed Tetrahedron Lett. 2000, 41, 471-475. Lee, J. W.; Kim, K.; Kim K.
A Kinetically Controlled Molecular Switch Based on Bistable [2]-
leading to new nanotechnology.47 Rotaxane. Chem. Commun. 2001, 1042-1043.
With the discovery of new CB homologues and deriva- (13) Isobe, H.; Tomita, N.; Lee, J. W.; Kim, H.-J.; Kim, K.; Nakamura,
tives, new opportunities emerge as well as challenges. The E. Ternary Complexes Between DNA, Polyamine, and Cucurbituril.
Angew. Chem., Int. Ed. 2000, 39, 4257-4260.
mechanism of cyclization and the template effects are (14) Lim, Y.-b.; Kim,T.; Lee, J. W.; Kim, S.-m.; Kim, H.-J.; Kim, K.; Park,
issues to be more elaborately addressed. A major limita- J.-s. Self-Assembled Ternary Complex of Cationic Dendrimer,
tion has been direct functionalization of CB[6] or the Cucurbituril, and DNA: Noncovalent Strategy in Developing Gene
Delivery Carrier. Bioconjugate Chem. 2002, 13, 1181-1185.
homologues leading to their derivatives. Appending reac- (15) Kim, K. Mechanically Interlocked Structures Incorporating Cucur-
tive functionalities directly on the CB surface resulting in bituril. Chem. Soc. Rev. 2002, 31, 96-107. Lee, J. W.; Kim, K.
derivatives with well-defined structures would further Rotaxane Dendrimers. Top. Curr. Chem. 2003, 228, 111-140.
(16) Mock, W. L.; Irra, T. A.; Wepsiec, J. P.; Adhya, M. Catalysis by
broaden the scope of CB chemistry. The covalent func- Cucurbituril. The Significance of Bound-Substrate Destabilization
tionalization of CBs would pave the way to newer ap- for Induced Triazole Formation. J. Org. Chem. 1989, 54, 5302-
5308.
plications in the same manner as the upsurge in appli-
(17) Karcher, S.; Kornmuller, A.; Jekel, M. Cucurbituril for Water
cations of CDs after they were functionalized. CBs with Treatment. Part I: Solubility of Cucurbituril and Sorption of
specialized functions, such as chiral CBs with enantiose- Reactive Dyes. Water Res. 2001, 35, 3309-3316.
(18) Jeon, Y.-M.; Kim, J.; Whang, D.; Kim, K. A Molecular Container
lective properties, may find many uses including chiral Assembly Capable of Controlling Binding and Release of Its Guest
columns for chromatography. Finally, new CB analogues Molecules. J. Am. Chem. Soc. 1996, 118, 9790-9791.
can be synthesized adopting diverse synthetic routes (19) Flinn, A.; Hough, G. C.; Stoddart, J. F.; Williams, D. J. Decamethyl-
cucurbit[5]uril. Angew. Chem., Int. Ed. Engl. 1992, 31, 1475-1477.
resulting in receptors with yet unknown properties. With (20) Kim, J.; Jung, I.-S.; Kim, S.-Y.; Lee, E.; Kang, J.-K.; Sakamoto, S.;
a greater control over the synthesis strategy, discovery of Yamaguchi, K.; Kim, K. New Cucurbituril Homologues: Synthe-
such receptors is a distinct possibility. ses, Isolation, Characterization, and X-ray Crystal Structures of
Cucurbit[n]uril (n ) 5, 7, and 8). J. Am. Chem. Soc. 2000, 122,
Though CB[6] was discovered nearly a century ago, the 540-541.
addition of new CB homologues and derivatives has (21) Day, A.; Arnold, A. P.; Blanch, R. J.; Snushall, B. Controlling
Factors in the Synthesis of Cucurbituril and Its Homologues. J.
widened the scope further. The past two years have
Org. Chem. 2001, 66, 8094-8100.
witnessed a heightened interest in CB chemistry. However, (22) Chakraborty, A.; Wu, A.; Witt, D.; Lagona, J.; Fettinger, J. C.;
the real potential of these intriguing molecular receptors Isaacs, L. Diastereoselective Formation of Glycoluril Dimers:
Isomerization Mechanism and Implications for Cucurbit[n]uril
is only beginning to be defined. Synthesis. J. Am. Chem. Soc. 2002, 124, 8297-8306.
(23) Day, A. I.; Blanch, R. J.; Coe, A.; Arnold, A. P. The Effects of Alkali
We gratefully acknowledge the Creative Research Initiative Metal Cations on Product Distributions in Cucurbit[n]uril Synthe-
Program and International Joint R&D Projects of the Korean sis, J. Incl. Phenom. Macrocylic Chem. 2002, 43, 247-250.
(24) Park, S.-H.; Kim, K., unpublished work.
Ministry of Science and Technology for support of this work, as (25) Kim, H.-J.; Jeon, W. S.; Ko, Y. H.; Kim, K. Inclusion of Methyl
well as partial support by the Brain Korea 21 Program of the viologen in Cucurbit[7]uril. Proc. Natl. Acad. Sci. U.S.A. 2002, 99,
Korean Ministry of Education. 5007-5011.
(26) Ong, W.; Gomez-Kaifer, M.; Kaifer, A. E. Cucurbit[7]uril: A Very
Effective Host for Viologens and Their Cation Radicals. Org. Lett.
References 2002, 4, 1791-1794.
(1) Behrend, R.; Meyer, E.; Rusche, F. Condensation Products from (27) Mirzoian, A.; Kaifer, A. E. Reactive Pseudorotaxanes: Inclusion
Glycoluril and Formaldehyde. Liebigs Ann. Chem. 1905, 339, Complexation of Reduced Viologens by the Host -Cyclodextrin
1-37. and Heptakis(2,6-di-O-methyl)--Cyclodextrin. Chem. Eur. J. 1997,
(2) Freeman, W. A.; Mock, W. L.; Shih, N.-Y. Cucurbituril. J. Am. 3, 1052-1058.
Chem. Soc. 1981, 103, 7367-7368. (28) Jeon, W. S.; Kim, H.-J.; Lee, C.; K. Kim, Control of the Stoichi-
(3) Mock, W. L. Cucurbituril. In Comprehensive Supramolecular ometry in Host-guest Complexation by Redox Chemistry of
Chemistry; Vogtle, F., Ed.; Pergamon: Oxford, 1996; Vol. 2, pp Guests: Inclusion of Methyl-viologen in Cucurbit[8]uril. Chem.
477-493. Commun. 2002, 1828-1829.
(29) Kim, H.-J.; Heo, J.; Jeon, W. S.; Lee, E.; Kim, J.; Sakamoto, S.; (40) Zhang, X. X.; Krakowiak, K. E.; Xue, G.; Bradshaw, J. S.; Izatt, R.
Yamaguchi, K.; Kim, K. Selective Inclusion of a Hetero-Guest Pair M. A Highly Selective Compound for Lead: Complexation Studies
in a Molecular Host: Formation of Stable Charge-Transfer Com- of Decamethylcucurbit[5]uril with Metal Ions. Ind. Eng. Chem. Res.
plexes in Cucurbit[8]uril. Angew. Chem., Int. Ed. 2001, 40, 1526- 2000, 39, 3516-3520.
1529. (41) Buschmann, H.-J.; Cleve, E.; Jansen, K.; K. Wego, A.; Schollmeyer,
(30) Kim, K.; et al. Unpublished work. E. Complex Formation Between Cucurbit[n]urils and Alkali,
(31) Jeon, Y. J.; Bharadwaj, P. K.; Choi, S.W.; Lee, J. W.; Kim, K. Alkaline Earth and Ammonium Ions in Aqueous Solution. J. Incl.
Supramolecular Amphiphiles: Spontaneous Formation of Vesicles Phenom. Macrocyclic Chem. 2001, 40, 117-120.
Triggered by Formation of a Charge-Transfer Complex in a Host. (42) Jansen, K.; Buschmann, H.-J.; Wego, A.; Dopp, D.; Mayer, C.;
Angew. Chem., Int. Ed. 2002, 41, 4474-4476.
Drexler, H.-J.; Holdt, H.-J.; Schollmeyer, E. Cucurbit[5]uril,
(32) Kim, S.-Y.; Jung, I.-S.; Lee, E.; Kim, J.; Sakamoto, S.; Yamaguchi,
Decamethylcucurbit[5]uril and Cucurbit[6]uril. Synthesis, Solubil-
K.; Kim, K. Macrocycles within Macrocycles: Cyclen, Cyclam, and
Their Transition Metal Complexes Encapsulated in Cucurbit[8]- ity and Amine Complex Formation. J. Incl. Phenom. Macrocyclic
uril. Angew. Chem., Int. Ed. 2001, 40, 2119-2121. Chem. 2001, 39, 357-363.
(33) Day, A. I.; Blanch, R. J.; Arnold, A. P.; Lorenzo, S.; Lewis, G. R.; (43) Kellersberger, K. A.; Anderson, J. D.; Ward, S. M.; Krakowiak, K.
Dance, I. A Cucurbituril-Based Gyroscane. Angew. Chem., Int. Ed. E.; Dearden, D. V. Encapsulation of N2, O2, Methanol, or Aceto-
2002, 41, 275-277. nitrile by Decamethylcucurbit[5]uril(NH4+)2 Complexes in the Gas
(34) Jon, S. Y.; Ko, Y. H.; Park, S.-H.; Kim, H.-J.; Kim, K. A Facile, Phase: Influence of the Guest on Lid Tightness. J. Am. Chem.
Stereoselective [2 + 2] Photoreaction Mediated by Cucurbit[8]- Soc. 2001, 123, 11316-11317.
uril. Chem. Commun. 2001, 1938-1939. (44) Miyahara, Y.; Abe, K.; Inazu, T. Molecular Molecular Sieves:
(35) Kim, K.; Jeon, Y. J.; Kim, S.-Y.; Ko, Y. H. Inclusion Compound Lid-Free Decamethylcucurbit[5]uril Absorbs and Desorbs
Comprising Cucurbituril Derivatives as Host Molecule and Phar- Gases Selectively. Angew. Chem., Int. Ed. 2002, 41, 3020-3023.
maceutical Composition Comprising the Same. PCT Int. Appl. (45) Zhao, J.; Kim, H.-J.; Oh, J.; Kim, S.-Y.; Lee, J. W.; Sakamoto, S.;
2003, WO 0324978 A1 20030327. Yamaguchi, K.; Kim, K. Cucurbit[n]uril Derivatives Soluble in
(36) Marquez, C.; Nau, W. M. Polarizabilities Inside Molecular Contain- Water and Organic Solvents. Angew. Chem., Int. Ed. 2001, 40,
ers. Angew. Chem., Int. Ed. 2001, 40, 4387-4390. 4233-4235.
(37) Lorenzo, S.; Day, A. I.; Craig, D.; Blanch, R. J.; Arnold, A. P.; Dance, (46) Isobe, H.; Sato, S.; Nakamura, E. Synthesis of Disubstituted
I. The First Endoannular Metal Halide-Cucurbituril: cis-SnCl4- Cucurbit[6]uril and Its Rotaxane Derivative. Org. Lett. 2002, 4,
(OH2)2@Cucurbit[7]uril. CrystEngComm 2001, 49, 1-7. 1287-1289.
(38) Blanch, R. J.; Sleeman, A. J.; White, T. J.; Arnold, A. P.; Day, A.
(47) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F. Artificial
I. Cucurbit[7]uril and o-Carborane Self-Assemble to Form a
Molecular Machines. Angew. Chem., Int. Ed. 2000, 39, 3348-3391.
Molecular Ball Bearing. Nano Lett. 2002, 2, 147-149.
(39) N.-Y. Shih, Ph.D. Thesis, University of Illinois at Chicago, Chicago,
1981. AR020254K