Reversible control of assembly and disassembly of interlocked supermolecules

Article abstract of DOI:10.1021/jo0490548

Two kinds of interlocked supramolecular complexes that display stimulus-responsive assembly and disassembly have been described. One is a pseudorotaxane driven by hydrogen-bonding interactions between rings 2a and 2b and rods 1a and 1b. The rods contain a

Full text of DOI:10.1021/jo0490548

Rever sible Con tr ol of Assem bly a n d Disa ssem bly of In ter lock ed
Su p er m olecu les
Kyoung-J in Chang, Young-J ae An, Hyounsoo Uh, and Kyu-Sung J eong*
Center for Bioactive Molecular Hybrids and Department of Chemistry, Yonsei University,
Seoul 120-749, Korea
ksjeong@yonsei.ac.kr
Received J une 5, 2004
Two kinds of interlocked supramolecular complexes that display stimulus-responsive assembly and
disassembly have been described. One is a pseudorotaxane driven by hydrogen-bonding interactions
between rings 2a and 2b and rods 1a and 1b. The rods contain a binding site for the ring as well
as a stimulus-responsive diazo group, both of which are conformationally constrained in parallel
by connecting them to a rigid xanthene skeleton. The trans isomer of 1a bearing a rigid binding
site cannot form the pseudorotaxanes with the rings 2a and 2b because the neighboring diazophenyl
group sterically shields the binding site. However, when trans-1a was converted to the corresponding
cis-1a by UV light, the pseudorotaxanes are immediately formed with association constants of 70
( 10 M-1 and (1.1 ( 0.1) × 103 M-1 for 2a and 2b, respectively, in CDCl3 at 24 ( 1 °C. The
pseudorotaxanes are completely disassembled into their molecular component when heated at 80-
85 °C for 20 min. The assembly and disassembly processes can be reversibly cycled by repeating
irradiation and heating alternatively. In the case of the rod 1b that possesses a flexible binding
site, both cis and trans isomers can form the corresponding pseudorotaxanes with association
constants of (2.0 ( 0.3) × 102 M-1 for 2a and trans-1b and of (7.4 ( 0.5) × 102 M-1 for 2a and
cis-1b in CDCl3 at 24 ( 1 °C. In this system, therefore, external stimuli can modulate the relative
distribution of the pseudorotaxane and its components. Finally, the work was extended to the
construction of a kinetically more stable molecular machine based on a rotaxane-like complex 10‚
11 between a metallocycle 11 and a dumbbell 10. In this system, the complex and its components
1
showed separate sets of the signals, not the averaged, in H NMR spectroscopy as expected by the
increased kinetic stability.
In tr od u ction
components that cannot be separated without breaking
a covalent bond. Two components may reversibly change
their relative positions within the interlocked entities,
so-called co-conformations,2 to generate a thermodynam-
ically stable state when an external stimulus is applied.
On the other hand, the pseudorotaxane is a supramo-
lecular complex, and its assembly and disassembly may
be reversibly controlled at will. The switching capability
of these supermolecules is one of the most important
features required for construction of artificial molecular-
level machines.
The supramolecular states of the co-conformations
(rotaxanes and catenanes) or the assembly/disassembly
(pseudorotaxanes) can be controlled by modulation of
noncovalent interactions. The most widely used method
for this purpose is electro- and photochemical redox
chemistry3 that alters effectively the strength of nonco-
valent interactions including hydrogen bonds and metal
coordination. The other is the acid-base chemistry that
induces the protonation and deprotonation at the recog-
nition sites, thus greatly affecting the hydrogen-bonding
capability.4 Light energy has been also used for operation
Interlocked supermolecules such as rotaxanes, cat-
enanes, and pseudorotaxanes have attracted a great deal
of attention in recent years because of their potential
applications to molecular electronics in the future.1
Rotaxanes and catenanes are mechanically interlocked
supermolecules comprised of two distinct molecular
* To whom correspondence should be addressed. Fax: (+) 82-2-364-
7050. Tel: (+) 82-2-2123-2643.
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10.1021/jo0490548 CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/01/2004
6556
J . Org. Chem. 2004, 69, 6556-6563

Assembly and Disassembly of Interlocked Supermolecules
of artificial molecular machines.5,6 In particular, in the
molecular machines based on the diazo functionality, the
trans isomer of the rod is nicely threaded but the cis
isomer poorly fitted in the ring owing to its inherent bent
shape.5
Herein we describe design, self-assembly, and proper-
ties of interlocked supramolecular complexes 1‚2 that
display stimulus-responsive assembly and disassembly
and therefore function like a molecular machine (Figure
1).7 Reversible switching of two supramolecular states
stems from trans-cis isomerization of the diazo func-
tionality in the rod components 1a and 1b, which can be
reversibly controlled by light and thermal stimulations.
The working principle of new molecular machines is
different from the previous diazo-based ones,5 and the
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F IGURE 1. Pseudorotaxane-based molecular machines.
efficiency in the regulation of the supramolecular states
is one of the highest among light-driven molecular
machines reported to date. A rotaxane-like complex 10‚
11 was also prepared from a metallocycle and a dumbbell
and was proven to be a kinetically more stable molecular
machine compared to the pseudorotaxane-based ones 1‚
2.
Resu lts a n d Discu ssion
Design P r in cip le. The pseudorotaxane-based molec-
ular machine designed here is shown schematically in
Figure 1. A main driving force for the assembly of a ring
and a rod is hydrogen-bonding interactions. In the trans
isomer of the rod, the diazo group sterically interferes
the ring encircling the binding site, and consequently,
the pseudorotaxane cannot be formed. However, when
UV light is applied, thus inducing isomersation into the
cis isomer, the binding site is unlocked so that the ring
can be threaded in it. For this purpose, a xanthene
derivative has been found to be an ideal scaffold that
places the binding site and the diazo unit in the proper
positions.
(5) For examples of light-driven machines based on diazo functional-
ity, see: (a) Murakami, H.; Kawabuchi, A.; Kotoo, K.; Kunitake, M.;
Nakashima, N. J . Am. Chem. Soc. 1997, 119, 7605-7606. (b) Asakawa,
M.; Ashton, P. R.; Balzani, V.; Brown, C. L.; Credi, A.; Matthews, O.
A.; Newton, S. P.; Raymo, F. M.; Shipway, A. N.; Spencer, N.; Quick,
A.; Stoddart, J . F.; White, A. P.; Williams, D. J . Chem. Eur. J . 1999,
5, 860-875. (c) Balzani, V.; Credi, A.; Marchioni, F.; Stoddart, J . F.
Chem. Commun. 2001, 1860-1861.
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Comprehensive Supramolecular Chemistry; Lehn, J .-M., Chair Ed.;
Atwood, J . L., Davies. J . E. D., MacNicol, D. D., Vo¨gtle, F., Eds.;
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42, 2296-2300. (g) Crowley, J . D.; Goshe, A. J .; Steele, I. M.; Bosnich,
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Tetralactam macrocycles 2a and 2b were chosen as the
ring component in this study because they are sufficiently
soluble in noncompetitive solvents such as chloroform
and 1,1,2,2-tetrachloroethane.8 On the basis of our previ-
ous studies,9 terephthalamido and adipamido function-
alities that have strong hydrogen-binding affinities to 2a
and 2b are utilized as the binding site in rods 1a and
1b.
(7) For a preliminary communication, see: J eong, K.-S.; Chang, K.-
J .; An, Y.-J . Chem. Commun. 2003, 1450-1451.
J . Org. Chem, Vol. 69, No. 20, 2004 6557

Chang et al.
SCHEME 1. Syn th esis of Rod s 1a a n d 1b a
followed by reduction (H2-Raney Ni, 93%). Alternatively,
bromination (Br2/Fe, 61%) of 3 gave a dibromoxanthene
which was converted into a dicarboxylic acid 5 (n-BuLi
then CO2, 83%)11 and then treated with NaN3/H2SO4 to
give the xanthenediamine 6 in 83% yield.13 Condensation
of 6 with 1 equiv of nitrosobenzene under acidic condi-
tions gave azo compound 7 in 74% yield.14 The rod 1a
containing a rigid binding site was prepared in 26% yield
from the reaction of terephthaloyl dichloride with 1 equiv
each of 7 and diethylamine in one pot. Finally, the other
rod 1b was prepared in 74% yield in the presence of 2,2-
dimethylpropionyl chloride by coupling of 7 and adip-
amide monoacid 8.
The rods 1a and 1b exist as mixtures of the trans and
cis isomers, and the former is a major component (96 (
2%) under ambient conditions based on the 1H NMR
spectra. The relative populations of the cis isomers
increase up to 76 ( 2% based on the 1H NMR integration
when irradiated with UV light (365 nm)15 for approxi-
mately 10 min. The 1H NMR spectra of trans and cis
isomers are noticeably different from each other (Figure
2a). In particular, the signals for the aromatic hydrogens
Hd* and He* of the diarylazo unit in the cis isomer were
considerably upfield shifted (∆δ ) 0.9-1.2 ppm) relative
to those in the trans isomer. These spectral behaviors
are consistent with computer modeling (Figure 3),16
showing that two aryl planes of the diarylazo units stack
together in the cis isomer, thus making the aromatic
signals upfield shifted due to ring current effects. As
shown in Figure 2b, the absorption band (λmax ) 358 nm),
a characteristic band of the trans isomer, is greatly
reduced in the UV-vis spectrum as expected for the
trans-cis isomerization of the diarylazo functionality.17
a
Reaction conditions: (i) HNO3/CH3CO2H, rt, 49%; (ii) Raney
Ni, H2, THF, rt, 93%; (iii) Br2, Fe, CHCl3, rt, 61%; (iv) n-BuLi(1.6
M in hexane), CO2 gas, concd HCl, THF, 83%; (v) NaN3, H2SO4,
CHCl3, 83%; (vi) nitrosobenzene, CH3CO2H, CHCl3, 74%; (vii)
Et3N, CHCl3, then Et2NH, 26%; (viii) (CH3)3CCOCl, i-Pr2NEt,
CH2Cl2, 74%.
Assem bly a n d Disa ssem bly of P seu d or ota xa n es.
The initial study for the pseudorotaxane-based machine
was conducted with a rod 1a and a ring 2a . When
thermally stable trans-1a was added to a solution of 2a
at room temperature, no change in the NH chemical
Syn th esis a n d Isom er iza tion . Tetralactam macro-
cycles 2a and 2b were synthesized according to literature
procedures.10 Syntheses of rod molecules 1a and 1b
containing diazo functionality are outlined in Scheme 1.
A xanthenediamine 6 was synthesized in two different
manners from 2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene
(3), which was derived from xanthene-9-one following
literature procedure.11 The xanthenediamine 6 was first
prepared by nitration(HNO3/CH3COOH, 49%) of 3,12
1
shifts was observed in the H NMR spectrum. However,
the NH signal of the ring was moderately downfield
shifted (∆δ ) ∼0.25 ppm) when trans-1a was converted
into cis-1a by UV irradiation (365 nm). The association
constant between 2a and cis-1a was calculated to be only
70 ( 10 M-1 in CDCl3 at 24 ( 1 °C (Table 1).18 Although
this system demonstrated that our new system was
working as designed, the binding affinity between two
(8) For some examples of rotaxanes, pseudorotaxanes, and catenanes
based on tetralactam macrocycles, see: (a) Vo¨gtle, F.; Du¨nnwald, T.;
Schmidt, T. Acc. Chem. Res. 1996, 29, 451-460. (b) Schalley, C. A.;
Beizai, K.; Vo¨gtle, F. Acc. Chem. Res. 2001, 34, 465-476. (c) Reuter,
C.; Wienand, W.; Schmuck, C.; Vo¨gtle, F. Chem. Eur. J . 2001, 7, 1728-
1733. (d) Gatti, F. G.; Leigh, D. A.; Nepogodiev, S. A.; Slawin, A. M. Z.
Teat, S. J .; Wong, J . K. Y. J . Am. Chem. Soc. 2001, 123, 5983-5989.
(e) Asakawa, M.; Brancato, G,; Fanti, M.; Leigh, D. A.; Shimizu, T.;
Slawin, A. M. Z.; Wong, J . K. Y.; Zerbetto, F.; Zhang, S. J . Am. Chem.
Soc. 2002, 124, 2939-2950. (f) Schalley, C. A.; Silva, G.; Nising, C. F.;
Linnartz, P. Helv. Chim. Acta 2002, 85, 1578-1596. (g) Leigh, D. A.;
Wong, J . K. Y.; Dehez, F.; Zerbetto, F. Nature 2003, 424, 174-179.
(9) (a) J eong, K.-S.; Cho, Y. L.; Song, J . U.; Chang, H.-Y.; Choi, M.-
G. J . Am. Chem. Soc. 1998, 120, 10982-10983. (b) J eong, K.-S.; Cho,
Y. L.; Chang, S.-Y.; Park, T.-Y.; Song, J . U. J . Org. Chem. 1999, 64,
9459-9466. (c) J eong, K.-S.; Lee, J . W.; Park, T.-Y.; Chang, S.-Y. Chem.
Commun. 1999, 2069-2070.
(10) (a) Hunter, C. A. J . Chem. Soc., Chem. Commun. 1991, 749-
751. (b) Hunter, C. A. J . Am. Chem. Soc. 1992, 114, 5303-5311. (c)
Vo¨gtle, F.; Meier, S.; Hoss, R. Angew. Chem., Int. Ed. Engl. 1992, 33,
1767-1770. (d) Hunter, C. A.; Shannon, R. J . Chem. Commun. 1996,
1361-1362.
(11) (a) Nowick, J . S.; Ballester, P.; Ebmeyer, F.; Rebek, J ., J r. J .
Am. Chem. Soc. 1990, 112, 8902-8906. (b) Hamann, B. C.; Branda,
N. R.; Rebek, J ., J r. Tetrahedron Lett. 1993, 34, 6837-6840.
(12) Tashiro, M.; Mataka, S.; Takezaki, Y.; Takeshita, M.; Arimura,
T.; Tsuge, A.; Yamato, T. J . Org. Chem. 1989, 54, 451-458.
(13) (a) Wolff, H. Org. React. 1946, 3, 307-336. (b) Wiberg, K. B.;
Ross, B. S.; Isbell, J . J . McMurdie, N. J . Org. Chem. 1993, 58, 1372-
1376.
(14) (a) Davey, M. H.; Lee, V. Y.; Miller R. D.; Marks, T. J . J . Org.
Chem. 1999, 64, 4976-4979. (b) Shuangxi W.; Rigiberto, C. A. Org.
Lett. 2001, 3, 3831-3834.
(15) The solution in a NMR tube or in a UV cuvette was directly
irradiated with a UV light source (365 nm, 100 W long wave, UVP,
Inc., B-100A).
(16) The energy-minimized structures were generated with the
MM2* force field implemented in MacroModel 7.1 program on a Silicon
Graphics Indigo IMPACT workstation: Mohamedi, F.; Richards, N.
G. J .; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.;
Hendrickson, T.; Still, W. C. J . Comput. Chem. 1990, 11, 440-467.
(17) (a) Tamai, N.; Miyasaka, H. Chem. Rev. 2000, 100, 1875-1890.
(b) Dugave, C.; Demange, L. Chem. Rev. 2003, 103, 2475-2532.
(18) The association constant was calculated by nonlinear least-
squares fitting of the titration curve, plotting NH chemical shifts of
the ring vs equivalents of the rod. See: (a) Macomber, R. S. J . Chem.
Educ. 1992, 69, 375-378. (b) Fielding, L. Tetrahedron 2000, 56, 6151-
6169 and also see the Experimental Section for more details.
6558 J . Org. Chem., Vol. 69, No. 20, 2004

Assembly and Disassembly of Interlocked Supermolecules
F IGURE 3. Energy-minimized structures of trans-1a and cis-
1a using the MM2* force field implemented in MacroModel
7.1 program.
TABLE 1. Associa tion Con sta n ts (Ka , M-1) of th e Rod s
a n d Rin gs a t 24 ( 1 °C in CDCl3
association constant (Ka, M-1
)
rod
ring
trans rod cis rod
1a
1a
1b
10
2a
2b
2a
11
a
a
70 ( 10
(1.1 ( 0.1) × 103
(7.4 ( 0.5) × 102
(3.0 ( 0.2) × 102
(2.0 ( 0.3) × 102
(1.0 ( 0.1) × 102
Too small to determine the binding affinity (Ka < 1 M-1).
a
(Figure 4b), the chemical shift change of the ring NH
signal is negligible (∆δ ∼0.02 ppm), implying that the
trans isomer cannot form the pseudorotaxane complex
as expected. However, the NH signal was considerably
downfield shifted from 8.82 to 9.96 ppm on irradiation
of the solution, which results in an increase of the cis-1a
population up to approximately 78% (Figure 4c). The NH
signal came back to the original position upon heating
the solution at 80-85 °C for 20 min, a process which
converted cis-1a to trans-1a (Figure 4d). As illustrated
in Figure 4 (inset), the assembly and disassembly of the
pseudorotaxane 1a ‚2b can be repeatedly cycled by alter-
nating irradiation and heating. The association constant
between 2b and cis-1a was found to be (1.1 ( 0.1) × 103
M-1 in CDCl3 at 24 ( 1 °C.18 In addition, the association
constant between 2b and cis-1a was (5.2 ( 0.1) × 103
M-1 at 5 °C.
Another approach we examined to augment the bind-
ing affinity between two components is to modify the
binding site in the rod into more flexible adipamide
functionality as in the rod 1b. In contrast to the rigid
rod 1a , addition of trans-1b to a C2D2Cl4 solution of the
ring 2a induces the NH signal considerably downfield
shifted (∆δ ∼0.70 ppm, Figure 5b). This result is not
surprising because the binding site in trans-1b is flexible
F IGURE 2. (a) Partial 1H NMR spectra of 1a before (bottom)
and after (top) UV irradiation (10 min, cis/ trans ) 78:22) and
(b) UV-vis spectral changes of 1a (2.0 × 10-5 M in CHCl3)
upon irradiation for 0, 2, 4, 6, and 8 s.
components was too small for efficient assembly of the
pseudorotaxane in solution.
To increase the binding affinity, we first modified the
ring component. Recently, we reported that binding
affinities between tetralactam macrocycles and diamide
guests greatly increased when electron-withdrawing
groups were introduced at the para position of the
pyridine ring.19 A nitro-substituted tetralactam 2b was
therefore prepared and used as the ring for more efficient
1
formation of the pseudorotaxane. The H NMR spectra
nicely illustrate a dramatic difference in the binding
affinities of 2b with two isomers, trans-1a and cis-1a
(Figure 4).
When trans-1a (4 equiv) was added to a solution of the
ring 2b (2.0 × 10-3 M) in C2D2Cl4 at room temperature
(19) (a) Chang, S,-Y.; Kim, H. S.; Chang, K.-J .; J eong, K.-S. Org.
Lett. 2004, 6, 181-184. (b) Carver, F. J .; Hunter, C. A.; Shannon, R.
J . J . Chem. Soc., Chem. Commun. 1994, 1277-1280. (c) Bradshaw, J .
S.; Mass, G. E.; Lamb, J . D.; Izatt, R. M.; Christensen, J . J . J . Am.
Chem. Soc. 1980, 102, 467-474.
J . Org. Chem, Vol. 69, No. 20, 2004 6559

Chang et al.
be (2.0 ( 0.3) × 102 M-1 and (7.4 ( 0.5) × 102 M-1
,
respectively, in CDCl3 at 24 ( 1 °C. It is also worth
mentioning that the binding affinity of cis-1b is 1 order
of the magnitude higher than that of the cis-1a bearing
a rigid binding site, terephthalamido functionality. Un-
like in the rod 1a , both isomers of the rod 1b can form
the corresponding pseudorotaxanes, and therefore exter-
nal stimuli can modulate the relative distribution of the
pseudorotaxane and its components.
Assem b ly a n d Disa ssem b ly of a R ot a xa n e-Lik e
Com p lex. We have extended this work to the construc-
tion of a kinetically more stable machine based on a
rotaxane-like complex20 between a metallocycle and a
stimulus-responsive dumbbell. We previously described
self-assembly of a metallocycle 11 from a bispyridyl
ligand9c and Stang’s palladium complex Pd(dppp)OTf2
21
and its application to the preparation of rotaxanes.22 In
dumbbell 10, the adipamide functionality was incorpo-
rated as the binding site for the metallocycle 11, a
diazoxanthene unit is attached to one end, and a bulky
tritylphenoxy stopper is placed at the other to prevent
the ring slipping off the dumbbell. The synthesis of
dumbbell 10 is outlined in Scheme 2.
F IGURE 4. Partial 1H NMR spectra in C2D2Cl4 at 25 °C of
(a) ring 2b (2.0 × 10-3 M) (b) ring 2b (2.0 × 10-3 M) + trans-
1a (4 equiv) (c) after 10 min irradiation (365 nm, ∼78% cis-
1a ) (d) after heating (80-85 °C) for 20 min. Inset: Plot of
chemical shift changes by alternating irradiation (9.96 ppm)
and heating (8.82 ppm).
Because of the weak, reversible nature of Pd(II)-N
coordinate bonds, a rotaxane-like complex is immediately
formed when two components 10 and 11 were mixed
1
together at room temperature. In the H NMR spectrum,
the complex 10‚11 showed separate signals from its
components 10 and 11 at room temperature in CDCl3
owing to a slow exchange on the 1H NMR time scale
(Figure 6). This is direct evidence for that the rotaxane-
like complex 10‚11 is kinetically more stable, relative to
the pseudorotaxanes 1‚2, which showed time-averaged
1H NMR signals as described above. Upon formation of
the complex 10‚11, two NH signals of metallocycle 11 are
downfield shifted (∆δ ) 1.1 ppm) as a result of hydrogen-
bond formation. Moreover, the methylene (-CH2-) sig-
nals in the adipamido binding site in the dumbbell are
upfield shifted (∆δ ) 0.8-1.2 ppm), suggesting that the
ring encircles around the adipamide part. Relative in-
tensities of the signals corresponding to the complex are
increased upon irradiation of the solution containing 10
and 11 (Figure 6c). This result implies that cis-10 binds
more strongly than trans-10 does. Indeed, the association
constants (Ka) of trans-10 and cis-10 were calculated to
be (1.0 ( 0.1) × 102 M-1 and (3.0 ( 0.2) × 102 M-1
,
1
respectively, on the basis of the H NMR integration in
CDCl3 at 25 °C.
F IGURE 5. Partial 1H NMR spectra in C2D2Cl4 at 25 °C of
(a) 2a (2.0 × 10-3 M), (b) 2a (2.0 × 10-3 M) + trans-1b (4
equiv), (c) after 10 min irradiation (365 nm, ∼76% cis-1b), and
(d) after heating (80-85 °C) for 20 min. Inset: Plot of chemical
shift changes by alternating irradiation (10.02 ppm) and
heating (9.60 ppm).
(20) The complex looks like a rotaxane with bulky stoppers at ends,
but behaves like a pseudorotaxane in equilibrium with its components.
The distinction between a pseudorotaxane and a rotaxane is sometimes
vague. See: (a) Ashton, P. R.; Baxter, I.; Fyfe, M. C. T.; Raymo, F. M.;
Spencer, N.; Stoddart, J . F.; White, A. J . P.; Williams, D. J . J . Am.
Chem. Soc. 1998, 120, 2297-2307. (b) Chiu, S.-H.; Rowan, S. J .;
Cantrill, S. J .; Glink, P. T.; Garrell, R. L.; Stoddart, J . F. Org. Lett.
2000, 2, 3631-3634. (c) J eppesen, J . O.; Becher, J .; Stoddart, J . F.
Org. Lett. 2002, 4, 557-560.
enough to rotate away from the diazo blocker, thus
minimizing the steric interference on the formation of
the pseudorotaxane with the ring 2a . Irradiation of the
solution with UV light leads to further shift of the NH
signal (Figure 5c), implying that cis-1b binds more
strongly to the ring 2a relative to trans-1b. Again, the
NH signal moves back to the original position when cis-
1b is transformed to the corresponding trans-1b by
heating the solution (Figure 5d). The association con-
stants of 2a with trans-1b and cis-1b are determined to
(21) (a) Stang, P. J .; Cao, D. H.; J . Am. Chem. Soc. 1994, 116, 4981-
4982. (b) Stang, P. J .; Cao, D. H.; Saito, S.; Arif, A. M. J . Am. Chem.
Soc. 1995, 117, 6273-6283.
(22) For rotaxanes derived from metallocycles, see: (a) J eong, K.-
S.; Choi, J . S.; Chang, S.-Y.; Chang, H.-Y. Angew. Chem., Int. Ed. 2000,
39, 1692-1695. (b) Hunter, C. A.; Low, C. M. R.; Packer, M. J .; Spey,
S. E.; Vinter, J . G.; Vysotsky, M. O.; Zonta, C. Angew. Chem., Int. Ed.
2001, 40, 2678-2682. (c) Chang, S.-Y.; Choi, J . S.; J eong, K.-S. Chem.
Eur. J . 2001, 7, 2687-2697. (d) Chang, S.-Y.; J ang, H.-Y.; J eong, K.-
S. Chem. Eur. J . 2003, 9, 1535-1541. (e) Chang, S.-Y.; J eong, K.-S. J .
Org. Chem. 2003, 68, 4014-4019.
6560 J . Org. Chem., Vol. 69, No. 20, 2004

Assembly and Disassembly of Interlocked Supermolecules
SCHEME 2. Syn th esis of Du m bbell 10a a n d
Str u ctu r e of Meta llocycle 11a
a
Reaction conditions: (i) (CH3)3CCOCl, i-Pr2NEt, rt, CH2Cl2,
74%.
Con clu sion
Reversible control of two supramolecular states that
may impart different physical, electrochemical, or optical
properties is a central feature for the construction of
molecular-level switches, machines, and devices. We here
describe interlocked supramolecular complexes that dis-
play stimulus-responsive assembly and disassembly driven
by hydrogen-bonding interactions. In this system, revers-
ible switching between two states is based on the trans-
cis isomerism of diazo functionality induced by light and
thermal energy, which leads to blocking and opening of
the binding site in the rod component. The design
principle and method applied in this study can be further
extended to design and construction of new molecular
machines using different pairs of molecular components.
1
F IGURE 6. Partial H NMR spectra (CDCl3, 25 °C) of (a) 11
(5.0 × 10-3 M), (b) 11 (5.0 × 10-3 M) + trans-10 (1 equiv), (c)
after 10 min irradiation (365 nm, 74% of cis-10), and (d) after
heating (80-85 °C) for 20 min. The NH signals for the free 11
(O, 0) and the rotaxane complex (b, 9) are indicated.
Exp er im en ta l Section
2,7-Di-t er t -b u t yl-9,9-d im e t h yl-9H -xa n t h e n e -4,5-d i-
a m in e (6). The compound 6 was prepared by two different
methods from 2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene (3).
Meth od A. To a suspension of 3 11 (2.7 g, 0.73 mol) in acetic
acid (300 mL) was added dropwise a solution of fuming nitric
acid (30 mL) in acetic acid (30 mL) over 1 h, and the solution
was stirred for 42 h at room temperature. Precipitates were
collected, washed with water and dried in a vacuum to yield
2,7-di-tert-butyl-9,9-dimethyl-4,5-dinitro-9H-xanthene 4 as white
133.5, 127.5, 113.1, 111.8, 110.4, 35.8, 32.5, 32.0, 31.0. Anal.
Calcd for C23H32N2O: C, 78.36; H, 9.15; N, 7.95. Found: C,
78.35; H, 9.13, N, 7.94.
Meth od B. 2,7-Di-tert-butyl-9,9-dimethyl-9H-xanthene-4,5-
dicarboxylic acid (5) was prepared from 2,7-di-tert-butyl-9,9-
dimethyl-9H-xanthene (3) according to literature procedures.11
Compound 5 (0.60 g, 1.4 mmol) was dissolved in CHCl3 (15
mL) containing fuming H2SO4 (0.10 mL), and NaN3 (0.34 g,
5.8 mmol) was added. The solution was stirred for 1.5 h at
room temperature, then for 1 h at 50-51 °C, and cooled to
room temperature. The pH of the solution was adjusted to 12-
13 with 1 N aqueous KOH, and the organic layer was washed
with water and brine. The solution was dried over anhydrous
Na2SO4, filtered, and concentrated to give 6 in 83% yield,
which gave the same physical and spectroscopic properties as
those of the sample obtained from method A.
solids (1.7 g, 49%): mp 296-298 °C; IR (KBr) 1600, 1265 cm-1
;
1H NMR (500 MHz, CDCl3) δ 7.78 (d, J ) 2.4 Hz, 2H), 7.65 (d,
J ) 2.4 Hz, 2H), 1.67 (s, 6H), 1.36 (s, 18H); 13C NMR (126
MHz, CDCl3) δ 147.7, 141.1, 139.3, 132.4, 127.5, 121.4, 35.8,
35.5, 32.6, 31.8. Anal. Calcd for C23H28N2O5: C, 66.97; H, 6.84;
N, 6.79. Found: C, 66.92; H, 6.87, N, 6.76.
To a solution of 4 (0.90 g, 2.4 mmol) in THF (50 mL) was
added a catalytic amount of Raney Ni, and the solution was
stirred under a H2 balloon for 1 h. The catalyst was filtered,
and the solvent was removed to give 6 as a white solid (0.71
2,7-Di-ter t-bu tyl-9,9-dim eth yl-5-ph en ylazo-9H-xan th en -
4-yla m in e (7). A solution of 6 (0.16 g, 0.45 mmol), nitrosoben-
zene (0.48 mg, 0.45 mmol), and two drops of acetic acid in
CHCl3 (6 mL) was stirred at room temperature under argon.14
After 12 h of stirring, the solution was diluted with CHCl3 (20
1
g, 93%): mp 210-211 °C; IR (KBr) 3400 cm-1; H NMR (500
MHz, CDCl3) δ 6.84 (s, 2H), 6.69 (s, 2H), 3.80 (s, 4H, NH2),
1.61(s, 6H), 1.30 (s, 18H); 13C NMR (126 MHz, CDCl3) δ 135.6,
J . Org. Chem, Vol. 69, No. 20, 2004 6561

Chang et al.
mL), washed with saturated NaHCO3 solution and brine, and
dried over anhydrous MgSO4. After concentration, the residue
was purified by silica gel column chromatography (CH2Cl2/n-
hexane ) 1:1) to give 7 as a reddish solid (0.12 g, 61%): mp
139.9, 137.0, 132.0, 131.2, 129.1, 126.5, 125.9, 122.6, 116.2,
115.3, 112.3, 41.9, 40.0, 37.8, 35.0, 34.9, 32.8, 31.5, 25.2, 25.0,
14.3, 13.1; HRMS (FAB) m/z calcd 625.4118 for C39H53N4O3,
found 625.4118. Anal. Calcd for C39H52N4O3: C, 74.96; H, 8.39;
N, 8.97; O, 7.68. Found: C, 74.99; H, 8.32; N, 8.93.
1
180-182 °C; IR (KBr) 3390, 1480 cm-1; H NMR (500 MHz,
CDCl3) δ 7.97 (d, J ) 6.7 Hz, 2H), 7.62-7.46 (m, 5H), 6.85 (d,
J ) 2.1 Hz, 1H), 6.73 (d, J ) 2.1 Hz, 1H), 4.04 (s, 2H, NH2),
1.69 (s, 6H), 1.34 (s, 9H), 1.32 (s, 9H); 13C NMR (126 MHz,
CDCl3) δ 146.7, 145.8, 140.6, 137.1, 135.6, 133.5, 133.0, 130.7,
129.2, 128.8, 127.0, 126.5, 123.4, 122.7, 116.6, 112.8, 112.1,
111.5, 35.1, 32.3, 32.2, 32.1. Anal. Calcd for C29H35N3O: C,
78.87; H, 7.99; N, 9.52. Found: C, 78.87; H, 7.98; N, 9.51.
Du m bbell 10. To a solution of compound 9 (0.31 g, 0.55
mmol) in CH2Cl2 (15 mL) at 0 °C (iced water bath) were added
2,2-dimethylpropionyl chloride (0.06 mL, 0.50 mmol) and N,N-
diisopropylethylamine (0.24 mL, 1.4 mmol). The solution was
stirred under argon for 1.5 h at room temperature, and 7 (0.20
g, 0.46 mmol) was added. After being stirred for 24 h at room
temperature, the mixture was washed with saturated NaHCO3
solution and brine and dried over anhydrous Na2SO4. After
concentration, the residue was purified by silica gel column
chromatography (CH2Cl2/MeOH ) 19:1) to give 10 as a reddish
solid (0.33 g, 73%): mp 83-85 °C; IR (KBr) 3300, 1640, 1480
5-Dieth ylca r ba m oylp en ta n oic Acid (8). A solution of
adipoyl dichloride (1.0 g, 5.5 mol), benzyl alcohol (0.57 mL,
5.5 mmol), 4-(N,N-dimethylamino)pyridine (DMAP, 65 mg, 0.1
equiv), and Et3N (1.5 mL, 11 mmol) in CH2Cl2 (15 mL) was
stirred for 14 h at room temperature under nitrogen. After
the solution was cooled to 0 °C (iced water bath), excess
diethylamine (2.3 mL, 4 equiv) was added, and the solution
was stirred for 1 h at room temperature. The mixture was
washed with 1 N HCl, saturated NaHCO3 solution, and brine
and dried over anhydrous Na2SO4. After concentration, the
residue was purified by silica gel column chromatography
(EtOAc/n-hexane ) 9:1) to yield 5-diethylcarbamoylpentanoic
acid benzyl ester as a colorless oil (0.56 g, 35%). This benzyl
ester was directly subjected to catalytic hydrogenolysis (H2
balloon, 5% Pd/C, MeOH) to give quantitatively 8 as colorless
oil: IR (thin film) 1729, 1606, 1281 cm-1; 1H NMR (500 MHz,
CDCl3) δ 3.37 (m, 2H), 3.30 (m, 2H), 2.40 (s, 2H), 2.34 (s, 2H),
1.71 (s, 4H), 1.18 (m, 3H), 1.11 (m, 3H); 13C NMR (126 MHz,
CDCl3) δ 177.7, 172.2, 42.1, 40.3, 33.9, 32.7, 24.7, 24.6, 14.3,
13.0. Anal. Calcd for C10H19NO3: C, 59.68; H, 9.52; N, 6.96;
O, 23.85. Found: C, 59.65; H, 9.55; N, 6.93.
1
cm-1; H NMR (500 MHz, CDCl3) δ 8.42 (s, 1H, NH), 8.18 (s,
1H), 7.95 (d, J ) 7.0 Hz, 2H), 7.65 (s, 1H), 7.60 (s, 1H), 7.55-
7.51 (m, 3H), 7.26-7.17 (m, 16H), 7.07 (d, J ) 8.7 Hz, 2H),
6.74 (d, J ) 8.7 Hz, 2H), 5.61 (s, 1H, -NH), 3.91-3.89 (m,
2H), 3.23-3.22 (m, 2H), 2.44-2.43 (m, 2H), 2.15-2.14 (m, 2H),
1.74-1.70 (m, 12H), 1.55-1.33 (m, 24H); 13C NMR (126 MHz,
CDCl3) δ 172.4, 170.9, 157.0, 153.3, 147.1, 146.4, 146.1, 145.4,
139.9, 138.7, 137.0, 132.1, 132.0, 131.1, 129.1, 127.4, 126.4,
125.9, 125.8, 122.6, 116.3, 115.3, 113.2, 112.4, 67.6, 39.4, 37.3,
36.3, 35.0, 34.9, 31.5, 29.6, 29.2, 26.7, 25.8, 25.1, 24.7; HRMS
(FAB) m/z calcd for C66H75N4O4 987.5788, found 987.5788.
Anal. Calcd for C66H74N4O4: C, 80.29; H, 7.55; N, 5.67; O, 6.48.
Found: C, 80.35; H, 7.40; N, 5.53.
1H NMR Tit r a t ion s a n d Ca lcu la t ion of Associa t ion
Con sta n ts. Chloroform was stored over 4 Å molecular sieves
and filtered through basic alumina prior to use. Two stock
solutions of a ring (2.0 × 10-3 M, e.g., 2a (1.90 mg) in 1.00 mL
of CDCl3) and a rod (2.0 × 10-2 M, e.g., 1a (39.0 mg) in 3.00
mL of CDCl3) were separately prepared at 24 ( 1 °C. The stock
solutions of rods were covered with aluminum foil for mini-
mum exposure to light. A 500 µL portion of the ring solution
was transferred to an NMR tube, and an initial NMR spectrum
was taken to determine the initial chemical shift of the free
ring. Aliquots of the rod solution (10 µL initially, then 80-
100 µL, and finally 300-700 µL) were added to the NMR tube
containing 500 µL of the ring solution. The spectrum was
recorded after each addition, and 13-18 data points were
obtained. This titration experiment generally took approxi-
mately 2 h, and before and after the titration, change in the
cis and trans ratio of the stock solution was negligible on the
basis of the 1H NMR integration. The association constants
were calculated to nonlinear least-squares fitting of the
titration curves,18 plotting the chemical shift changes of the
ring NH signal against the equivalent of the rod added.
Titration experiments were at least duplicated, and errors in
the association constants (Ka, M-1) were found to be less than
15% in all cases.
Rod 1a . To a solution of terephthaloyl dichloride (0.11 g,
0.56 mmol) in CHCl3 (35 mL) was added dropwise a solution
of 7 (0.25 g, 0.56 mmol) in CHCl3 (20 mL) containing triethyl-
amine (0.20 mL, 1.1 mmol) over 2 h at 0 °C (iced water bath)
under argon. After being stirred for 2.5 h at room temperature,
the solution was cooled to 0 °C, and excess diethylamine (0.30
mL, 3.4 mmol) was added. After being stirred for 1 h at room
temperature, the solution was washed with saturated NaHCO3
solution and brine, dried over anhydrous MgSO4, and concen-
trated. The residue was purified by silica gel column chroma-
tography (EtOAc) to give 1a as a reddish solid (90 mg, 26%):
mp 238-240 °C; IR (KBr) 3287, 1640, 1480 cm-1 1H NMR
;
(500 MHz, CDCl3) δ 8.98 (s, 1H, NH), 8.63 (s, 1H), 7.87 (d, J
) 7.8 Hz, 2H), 7.79 (s, 2H), 7.62 (s, 1H), 7.55 (s, 1H), 7.50-
7.41 (m, 3H), 7.24 (s, 1H), 7.09 (d, J ) 7.8 Hz, 2H), 3.58 (m,
2H), 3.16 (m, 2H), 1.74 (s, 6H), 1.59 (s, 6H), 1.38 (s, 9H); 13C
NMR (126 MHz, CDCl3) δ 164.5, 152.5, 147.1, 146.3, 141.4,
140.4, 137.1, 135.3, 131.6, 130.1, 128.8, 127.6, 126.5, 125.2,
123.3, 122.7, 122.0, 117.6, 116.3, 114.9, 112.9, 40.8, 34.9, 31.9,
31.7, 31.5, 13.2; HRMS (FAB) m/z calcd for
C41H49N4O3
645.3805, found 645.3805. Anal. Calcd for C41H48N4O3: C,
76.37; H, 7.50; N, 8.69. Found: C, 76.36; H, 7.48; N, 8.68.
As mentioned earlier, the rods 1a and 1b exist as mixtures
of the trans and cis isomers. Here, the populations of the trans
isomers can be increased >98% by heating at 80-85 °C for 20
min prior to the preparation of the stock solution for titration
experiments. On the other hand, the ratios of the cis isomers
were increased up to 76 ( 2% upon irradiation of the stock
solution, which were directly used for titration experiments.
In the case of 1a bearing a rigid binding site, the chemical
shift changes of the ring NH are attributed only to complex-
ation of the ring with cis-1a because the existing trans-1a
(∼22%) could not bind at all. Therefore, the association
constant can be calculated by simply correcting the concentra-
tions of cis-1a . For 1b with a flexible binding site, the situation
is more complicated because both isomers, trans-1b (24%) and
cis-1b (76%), bind to the ring and induce the NH chemical shift
changes under fast equilibrium. The association constant
between cis-1b and 2a was calculated to solve the following
equations simultaneously by an iterative procedure
Rod 1b. To a solution of compound 8 (0.21 g, 0.86 mmol) in
CH2Cl2 (15 mL) were added 2,2-dimethylpropionyl chloride
(0.11 mL, 0.79 mmol) and N,N-diisopropylethylamine (0.44
mL, 2.2 mmol) at 0 °C. The solution was stirred under argon
for 2 h at room temperature and cooled to 0 °C; 7 (0.32 g, 0.72
mmol) was then added. After being stirred for 24 h at room
temperature, the mixture was washed with water and brine
and dried over anhydrous Na2SO4. After concentration, the
residue was purified by silica gel column chromatography
(CH2Cl2/EtOAc ) 1:1) to give 1b as a reddish solid (0.33 g,
1
74%): mp 166-168 °C; IR (KBr) 3292, 1642, 1482 cm-1; H
NMR (500 MHz, CDCl3) δ 8.44 (s, 1H, NH), 8.19 (s,1H), 7.96
(d, J ) 7.4 Hz, 2H), 7.65 (s, 1H), 7.60 (s, 1H), 7.57-7.51 (m,
3H), 7.16 (s, 1H), 3.38-3.34 (m, 2H), 3.26-3.22 (m, 2H), 2.46-
2.43 (m, 2H), 2.29-2.26 (m, 2H), 1.77-1.74 (m, 4H), 1.70 (s,
6H), 1.38 (s, 9H), 1.36 (s, 9H), 1.13-1.09 (m, 6H); 13C NMR
(126 MHz, CDCl3) δ 71.6, 170.9, 153.3, 146.4, 146.0, 145.4,
6562 J . Org. Chem., Vol. 69, No. 20, 2004

Assembly and Disassembly of Interlocked Supermolecules
here fix θ ) 1.0 × 10-8
.
[HGt]
H + Gt ) HGt Kt )
H + Gc ) HGc Kc )
(1)
(2)
[H][Gt]
[HGt]n ) 0.5 × [([H]0 + [Gt]0 + Kt-1 - [HGc]n-1) -
[HGc]
([H] + [G ] + K -1 - [HGc]n-1)2 - 4[Gt]0([H]0 - [HGc]n-1)]
x
0
t
t
[H][Gc]
-1
[HGc]n ) 0.5[([H]0 + [Gc]0 + Kc - [HGt]n) -
where H, Gt, Gc, and HG stand for a ring, trans and cis
isomers, and a complex, respectively. The association constant
Kt can be determined independently using the trans isomer,
trans-1b (>98%). The observed chemical shift δobs at each
titration point is a weighted average of free ring H and two
complexes HGt and HGc that exist all in fast equilibrium under
titration conditions.
-1
([H] + [G ] + K
c
- [HGt]n)2 - 4[Gc]0([H]0 - [HGt]n)]
x
0
c 0
Here, [ ]0 represents total concentration of the species in the
bracket, and [ ]n-1 and [ ]n are concentrations obtained from
n-1th and nth iterations, respectively.
Ack n ow led gm en t. This work was supported by the
Korea Research Foundation (KRF-2002-041-C00163).
[Hfree
[H]0
]
[HGt]
[H]0
[HGc]
[H]0
δobs ) δfree
+ δHGt
+ δHGc
(3)
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal methods, 1H-1H NOESY of 1a , and 1H NMR spectral
changes of 1a ,b and 10 upon irradiation and heating. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Here, δfree, δHGt, and δHGc are the NH chemical shifts of free
ring H and two complexes HGt and HGc, respectively. The
concentration of two complexes, [HGt] and [HGc], can be
calculated by iterating the following equations until [|[HGt]n
- [HGt]n-1|]/[[HGt]n] eθ, where n is the number of iteration
and θ is an arbitrary small number. For the calculation, we
J O0490548
J . Org. Chem, Vol. 69, No. 20, 2004 6563