Toward interlocked molecules beyond catenanes and rotaxanes

Article abstract of DOI:10.1021/ol006187g

A linear bis secondary dialkylammonium ion-containing scaffold - based upon an anthracenyl core-has been synthesized. It has been demonstrated that it is possible to dock either one or two dibenzo[24]crown-8 (DB24C8) macrocycles onto this scaffold to affo

Full text of DOI:10.1021/ol006187g

ORGANIC
LETTERS
2000
Vol. 2, No. 19
2943-2946
Toward Interlocked Molecules beyond
Catenanes and Rotaxanes
Theresa Chang,† Aaron M. Heiss,† Stuart J. Cantrill,† Matthew C. T. Fyfe,†
,†
Anthony R. Pease,† Stuart J. Rowan,† J. Fraser Stoddart,* and
David J. Williams‡
Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles,
405 Hilgard AVenue, Los Angeles, California 90095-1569, and Chemical
Crystallography Laboratory, Department of Chemistry, Imperial College,
South Kensington, London SW7 2AY, U.K.
stoddart@chem.ucla.edu
Received June 9, 2000
ABSTRACT
A linear bis secondary dialkylammonium ion-containing scaffoldsbased upon an anthracenyl coreshas been synthesized. It has been
demonstrated that it is possible to dock either one or two dibenzo[24]crown-8 (DB24C8) macrocycles onto this scaffold to afford either a [2]-
or [3]pseudorotaxane, respectively. In solution, the association constants for the formation of each of these species has been quantified by
employing 1H NMR spectroscopy, and both species survive in the “gas phase” as evidenced by FAB mass spectrometry. Additionally, the
X-ray crystal superstructure of the [3]pseudorotaxane has been determined.
During the past 35 years, several different protocols have
been developed1 for the synthesis of mechanically interlocked
molecular compounds. These compounds, which include
catenanes,1,2 rotaxanes,1,3 and carceplexes,1,4 are constituted
of molecules composed of two or more components that
cannot be separated from each other for mechanical reasons.
The synthetic protocols used by chemists have evolved1 from
being all but statistical5 in the beginning to utilizing,
successfully, covalent,6 coordinative,7 and noncovalent8
templates under both kinetic9 and thermodynamic10 control.
We envisage the existence of a further class of interlocked
molecules, beyond catenanes and rotaxanes, that are remi-
niscent of carceplexes, yet distinguishable from them. In their
simplest forms, these molecules would consist of two
componentssa somewhat rigid scaffold and a reasonably
flexible netswherein the scaffold would be enmeshed by
the net. With a judicious choice of cores and branches, a
dendritic-like scaffold could be employed to template, under
(2) A catenane comprises two or more interlocking rings. (a) Hunter, C.
A. J. Am. Chem. Soc. 1992, 114, 5303-5311. (b) Leigh, D. A.; Murphy,
A.; Smart, J. P.; Deleuze, M. S.; Zerbetto, F. J. Am. Chem. Soc. 1998, 120,
6458-6467. (c) Andrievsky, A.; Ahuis, F.; Sessler, J. L.; Vo¨gtle, F.; Gudat,
D.; Moini, M. J. Am. Chem. Soc. 1998, 120, 9712-9713. (d) Ibukuro, F.;
Fujita, M.; Yamaguchi, K.; Sauvage, J.-P. J. Am. Chem. Soc. 1999, 121,
11014-11015. (e) McArdle, C. P.; Irwin, M. J.; Jennings, M. C.; Puddephatt,
R. J. Angew. Chem., Int. Ed. 1999, 38, 3376-3378. (f) Hamilton, D. G.;
Montalti, M.; Prodi, L.; Fontani, M.; Zanello, P.; Sanders, J. K. M. Chem.
Eur. J. 2000, 6, 608-617. (g) Balzani, V.; Credi, A.; Langford, S. J.; Raymo,
F. M.; Stoddart, J. F.; Venturi, M. J. Am. Chem. Soc. 2000, 122, 3542-
3543.
† University of California, Los Angeles.
‡ Imperial College, London.
(1) (a) Schill, G. Catenanes, Rotaxanes, and Knots; Acadmic: New York,
1971. (b) Cram, D. J.; Cram, J. M. In Container Molecules and their Guests;
Stoddart, J. F., Ed.; RSC: Cambridge, 1994. (c) Amabilino, D. B.; Stoddart,
J. F. Chem. ReV. 1995, 95, 2725-2828. (d) Hubin, T. J.; Kolchinski, A.
G.; Vance, A. L.; Busch, D. H. AdV. Supramol. Chem. 1999, 5, 237-357.
(e) Molecular Catenanes, Rotaxanes and Knots; Sauvage, J.-P., Dietrich-
Buchecker, C., Eds.; VCH-Wiley: Weinheim, 1999.
10.1021/ol006187g CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/19/2000

thermodynamic control, the formation of a matching net
comprising macrocycles and links around the scaffold. These
two components would be inseparable from each other prior
to cleavage of at least one covalent bond somewhere in the
molecular architecture. For example, the attempted departure
of one macrocycle of the net from the scaffold would
necessitate the passing of another macrocycle over the core
of the scaffold which would be impossible for steric reasons.
One of the simplest examples is portrayed in Figure 1 which
scaffold and then demonstrate that it will form a 2:1
complexsnamely, a [3]pseudorotaxaneswhich can subse-
quently be functionalized in order that the rigid linkers can
be introduced during the covalent modification of the initially
formed supermolecule. In this manner, the macrocycles can
be covalently linked together after self-assembly of the [3]-
pseudorotaxane, thus trapping the scaffoldswhich templates
the formation of the netsinside the net.
The well-established11 recognition motif that leads to the
threading of secondary dialkylammonium centers through
crown ethers, such as dibenzo[24]crown-8 (DB24C8), was
chosen as the starting point for this research. Herein, we (a)
report the synthesis (Scheme 1) of a bisammonium scaffold
Scheme 1a
Figure 1. A schematic representation of the approach to be taken
in the construction of a new class of interlocked molecular
compounds. The “+” sign on the scaffold represents NH2+ centers,
and the rectangles introduced at step A are crown ethers with [24]-
crown-8 constitutions. In step A, noncovalent bonding leads to
complexes (pseudorotaxanes) that are covalently linked in step B.
schematically illustrates the formation of an interlocked
molecule containing (i) a linear rigid scaffold comprising a
rod with a centrally located bulky core and (ii) a net-like
macropolycycle built of two macrocycles joined by two rigid
linkers. The first step toward making such an interlocked
molecular compound is to identify and synthesize a ditopic
a Reagents and conditions: i, PhMe, reflux; ii, NaBH4, MeOH,
H2O, rt; iii, HCl, H2O, rt; iv, NH4PF6, H2O, rt.
(3) A rotaxane is a molecule that comprises a dumbbell-shaped compo-
nent on which one or more rings are trapped mechanically by virtue of the
bulky nature of the dumbbell’s terminal groups. (a) Anelli, P. L.; Spencer,
N.; Stoddart, J. F. J. Am. Chem. Soc. 1991, 113, 5131-5133. (b) Kolchinski,
A. G.; Alcock, N. W.; Roesner, R. A.; Busch, D. H. Chem. Commun. 1998,
1437-1438. (c) Clegg, W.; Gimenez-Saiz, C.; Leigh, D. A.; Murphy, A.;
Slawin, A. M. Z.; Teat, S. J. J. Am. Chem. Soc. 1999, 121, 4124-4129. (d)
Kawasaki, H.; Kihara, N.; Takata, T. Chem. Lett. 1999, 1015-1016. (e)
Raehm, L.; Kern, J.-M.; Sauvage, J.-P. Chem. Eur. J. 1999, 5, 3310-3317.
(f) Seel, C.; Vo¨gtle, F. Chem. Eur. J. 2000, 6, 21-24. (g) Loeb, S. J.;
Wisner, J. A. Chem. Commun. 2000, 845-846.
(4) Jasat, A.; Sherman, J. C. Chem. ReV. 1999, 99, 931-967.
(5) (a) Wasserman, E. J. Am. Chem. Soc. 1960, 82, 4433-4434. (b)
Harrison, I. T.; Harrison, S. J. Am. Chem. Soc. 1967, 89, 5723-5724.
(6) Schill, G.; Lu¨ttringhaus, A. Angew. Chem., Int. Ed. Engl. 1964, 3,
546-547.
(7) (a) Sauvage, J.-P. Acc. Chem. Res. 1998, 31, 611-619. (b) Try, A.
C.; Harding, M. M.; Hamilton, D. G.; Sanders, J. K. M. Chem. Commun.
1998, 723-724. (c) Fujita, M. Acc. Chem. Res. 1999, 32, 53-61.
(8) (a) Glink, P. T.; Schiavo, C.; Stoddart, J. F.; Williams, D. J. Chem.
Commun. 1996, 1483-1490. (b) Philp, D.; Stoddart, J. F. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1154-1196. (c) Fyfe, M. C. T.; Stoddart, J. F.
Acc. Chem. Res. 1997, 30, 393-401. (d) Vo¨gtle, F.; Safarowsky, O.; Heim,
C.; Affeld, A.; Braun, O.; Mohry, A. Pure Appl. Chem. 1999, 71, 247-
251.
based on a 9,10-anthracenyl core and (b) demonstrate its
ability to form a [3]pseudorotaxane with DB24C8, both in
the solid state and in solution.
9,10-Bis(aminomethyl)anthracene12 was condensed with
2 equiv of benzaldehyde. The resulting diimine was reduced
to yield the diamine which was protonated and subjected to
13
counterion exchange to give the salt 1-H2‚2PF6 as a
crystalline compound. X-ray quality single crystals of the
[3]pseudorotaxane14 [(DB24C8)2‚1-H2][PF6]2 were obtained
by vapor diffusion of i-Pr2O into a 2:1 solution (CH2Cl2/
(11) (a) Kolchinski, A. G.; Busch, D. H.; Alcock, N. W. J. Chem. Soc.,
Chem. Commun. 1995, 1289-1291. (b) Ashton, P. R.; Chrystal, E. J. T.;
Glink, P. T.; Menzer, S.; Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker.
P. A.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2, 709-728. (c)
Fyfe, M. C. T.; Stoddart, J. F. AdV. Supramol. Chem. 1999, 5, 1-53. (d)
Yamaguchi, N.; Gibson, H. W. Angew. Chem., Int. Ed. 1999, 38, 143-
147.
(9) (a) Amabilino, D. B.; Ashton, P. R.; Pe´rez-Garc´ıa, L.; Stoddart, J. F.
Angew. Chem., Int. Ed. Engl. 1995, 34, 2378-2380. (b) Rowan, S. J.;
Stoddart, J. F. J. Am. Chem. Soc. 2000, 122, 164-165.
(12) Morgan, H.; Fukushima, H.; Taylor, D. M. J. Polym. Sci.: Part A:
Polym. Chem. 1994, 32, 1331-1340.
(13) Synthetic details for, and characterization data relating to compounds
1 and 1-H2‚2PF6, can be found in the Supporting Information.
(14) The crystalline 2:1 complex was also examined using FABMS. In
addition to a major peak at m/z 865, corresponding to a [2]pseudorotaxane
(10) (a) Fujita, M.; Ibukuro, F.; Hagihara, H.; Ogura, K. Nature 1994,
367, 720-723. (b) Kidd, T. J.; Leigh, D. A.; Wilson, A. J. J. Am. Chem.
Soc. 1999, 121, 1599-1600. (c) Cantrill, S. J.; Rowan, S. J.; Stoddart, J. F.
Org. Lett. 1999, 1, 1363-1366. (d) Rowan, S. J.; Stoddart, J. F. Org. Lett.
1999, 1, 1913-1916. (e) Furusho, Y.; Hasegawa, T.; Tsuboi, A.; Kihara,
N.; Takata, T. Chem. Lett. 2000, 18-19. (f) Chichak, K.; Walsh, M. C.;
Branda, N. R. Chem. Commun. 2000, 847-848. (g) Jeong, K.-S.; Choi, J.
S.; Chang, S.-Y.; Chang, H.-Y. Angew. Chem., Int. Ed. 2000, 39, 1692-
1695. (h) Ro, S.; Rowan, S. J.; Pease, A. R.; Cram, D. J.; Stoddart, J. F.
Org. Lett. 2000, 2, 2411-2414.
-
that has lost two of its PF6 counterions, there is a significant peak at m/z
-
1459, corresponding to the [3]pseudorotaxane with the loss of one PF6
counterion, as well as a prominent peak at m/z 657, representing the doubly
charged [3]pseudorotaxane without any counterions. A similar fragmentation
pattern has been reported for a related [3]pseudorotaxane in which the
2+
9,10-anthracenyl core of 1-H2 is replaced by a p-phenylene unit. See:
ref 11b.
2944
Org. Lett., Vol. 2, No. 19, 2000

MeNO2, 1:1) of DB24C8 and 1-H2‚2PF6. The X-ray analy-
sis15 of these crystals revealed (Figure 2) the anticipated
Figure 2. Solid-state superstructure of [(DB24C8)2‚1-H2]2+. The
hydrogen bonding geometries are X-H‚‚‚O, H‚‚‚O distances (Å)
and X-H‚‚‚O angles (deg); (a) 2.94, 2.09, 159; (b) 3.05, 2.23, 152;
(c) 3.17, 2.28, 174; (d) 3.00, 2.12, 167; (e) 3.41, 2.45, 172. The
centroid‚‚‚centroid and mean interplanar separations between ring
A and ring C and between ring C and ring B are 3.72, 3.39 and
3.61, 3.45 Å, respectively.
Figure 3. Partial 1H NMR spectrum (400 MHz) of a 1:1 mixture
of DB24C8 and 1-H2‚2PF6 (10 mM each) in CD3CN at 298 K.
The subscripts “c” and “uc” denote signals arising from protons
that are complexed and uncomplexed, respectively. The resonances
for the protons corresponding to the 1:1 [(DB24C8)‚1-H2][PF6]2
complexswhich contains one complexed and one uncomplexed
+
NH2 centersare labeled in red while those corresponding to the
2:1 complex are in blue.
threading of the benzylammonium portions of the dication
through the centers of the two DB24C8 macrocycles to create
a near Ci symmetric superstructure geometry. Intercomponent
equimolar mixture (10 mM each) of DB24C8 and 1-H2‚2PF6
in CD3CN gives rise to a H NMR spectrum with all four
1
bonding is via
a
combination of N+-H‚‚‚O and
speciessthe 1:1 and 2:1 complexes, in addition to the
uncomplexed speciesspresent. In this spectrum, downfield
shifts, relative to the signals for 1-H2‚2PF6, are observed for
C-H‚‚‚O hydrogen bonds as well as π-π stacking between
one of the catechol rings of each of the DB24C8 units and
the central portion of the anthracene unit of the dication
1-H22+. There are no interactions involving the terminal
phenyl rings.
+
the methylene protons (Ha and Hb) adjacent to the NH2
centers in the 2:1 (∆δ ) +0.02 and +0.83 ppm for Hac and
Hbc, respectively) and 1:1 complexes (∆δ ) +0.20 and
+0.93 ppm for Hac and Hbc, respectively). Similar downfield
shifts have been reported16 for the resonances of the
methylene protons in the 1H NMR spectra of pseudorotaxanes
formed between DB24C8 and a number of substituted
dibenzylammonium cations, including the sterically analo-
gous N-(9-anthracenylmethyl)-N-benzylammonium cation.17
It is also evident that the downfield shift for the benzylic
methylene protons (Hb) is more dramatic than that of the
anthracenyl methylene protons (Ha). This larger shift for the
former suggests that, upon complexation with DB24C8, the
benzylic methylene protons interact with the crown ether
through C-H‚‚‚O hydrogen bonds. In the 1:1 complex, the
signal for the anthracenyl methylene protons (Hauc) of the
free ammonium site is shifted upfield, possibly as a
The complexation of 1-H2‚2PF6 by DB24C8 in CD3CN
solution has also been investigated by 1H NMR spectroscopy
starting with different stoichiometric ratios of macrocyclic
polyether to scaffold. Since the equilibrium kinetics between
1
complexed and uncomplexed species are slow on the H
NMR time scale at 400 MHz, sharp peaks for these species
1
are observed (Figure 3) in the spectrum. In the H NMR
spectrum, obtained using a solution that is 50 mM in
DB24C8 and 10 mM in 1-H2‚2PF6, only signals for the [3]-
pseudorotaxane (2:1 complex) can be observed easily.
Conversely, a solution that is 10 mM in DB24C8 and 50
1
mM in 1-H2‚2PF6 gives rise to an H NMR spectrum of,
almost exclusively, the [2]pseudorotaxane (1:1 complex). An
(15) Crystal data for [(DB24C8)2‚1-H2][PF6]2‚2MeNO2: C78H94N2O16‚
2PF6‚2MeNO2, M ) 1727.6, monoclinic, P21 (No. 4), a ) 12.044(2), b )
25.471(2), c ) 14.632(2) Å, â ) 113.52(1)°, V ) 4115.7(8) Å3, Z ) 2, Dc
) 1.394 g cm-3, µ(Cu KR) ) 13.5 cm-1, F(000) ) 1812, T ) 183 K;
clear needles, 0.67 × 0.43 × 0.30 mm, refined based on F2 to give R1 )
0.062, wR2 ) 0.163 for 6389 independent observed absorption corrected
reflections [|Fo| > 4σ(|Fo|), 2θ e 128°] and 1091 parameters. The absolute
chirality of the structure was determined by an R-factor test [R1+ ) 0.0615,
(16) Ashton, P. R.; Campbell, P. J.; Chrystal, E. J. T.; Glink, P. T.;
Menzer, S.; Philp, D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Williams,
D. J. Angew. Chem., Int. Ed. Engl. 1995, 34, 1869-1871.
(17) Ashton, P. R.; Ballardini, R.; Balzani, V.; Go´mez-Lo´pez, M.;
Lawrence, S. E.; Mart´ınez-D´ıaz, M.-V.; Montalti, M.; Piersanti, A.; Prodi,
L.; Stoddart, J. F.; Williams, D. J. J. Am. Chem. Soc. 1997, 119, 10641-
10651.
-
R1 ) 0.0626].
Org. Lett., Vol. 2, No. 19, 2000
2945

consequence of shielding from a π-stacked catechol ring,
while the signal for the other anthracenyl methylene protons
(Hac) in the bound ammonium ion is shifted downfield (vide
supra), presumably as a result of being encircled by a
DB24C8 macrocycle. However, on complexation with a
second macrocycle to give the 2:1 complex, the chemical
shift changes are reversed so that the resonance correspond-
ing to Hac is only slightly downfield (vide supra) from that
for the free dication 1-H22+. The benzylic methylene protons
(Hb) show a similar behavior. In summary, the chemical
shifts of Ha and Hb depend on the conformations adopted
by the DB24C8 macrocycles in the 1:1 and 2:1 complexes
wherein the catechol rings can shield or not shield Ha and
Hb as the case might be, while C-H‚‚‚O interactions with
the macrocycles has a direct and profound effect. It is also
of interest to note that the resonances for the catechol ring
protons (He and Hf) in DB24C8 are shifted upfield (∆δ )
-0.65, -0.60 ppm for He and ∆δ ) -0.30 and -0.40 ppm
for Hf) in the 1:1 and 2:1 complexes, respectively, as a
consequence of their stacking with the anthracene core.
In solutions of known concentrations, the absolute con-
centrations of both complexes (2:1 and 1:1), DB24C8, and
1-H2‚2PF6 can be determined from integrations performed
five times larger than K2 suggests that a small amount of
negative cooperativity20 is in operation for the binding of
the second macrocycle. It appears that binding of the first
+
2+
macrocycle by an NH2 center in the 1-H2 dication
decreases very slightly the affinity of the other NH2+ center
for the second macrocycle. A possible reason for this slight
damping effect could be the fact that in the 1:1 complex
both catechol rings in the macrocycle can π-π stack with
the anthracene core if it adopts a U-shaped conformation,21
whereas when two macrocycles are bound to the dication
2+
1-H2 in the 2:1 complex, only two of the four catechol
rings can interact relatively strongly with the anthracene core.
Nonetheless, despite the small amount of negative cooper-
2+
ativity, we have established that dications of the type 1-H2
do bind to DB24C8. With appropriately functionalized crown
ethers, we hope to construct interlocked molecules of the
type depicted in Figure 1.
We have noted that monofunctionalization of the catechol
rings22 of DB24C8sthe obvious sites for functionalizing this
macrocycleswill reduce its symmetry and therefore result
in the production of a number of different isomeric com-
pounds. Since this situation increases the complexity of the
synthesis using DB24C8 macrocycles, we are looking to
develop23 macrocycles that retain the [24]crown-8 constitu-
tion yet can be functionalized in a symmetrical manner.
1
on resonances for suitable probe protons in the H NMR
spectra and thus the binding constants can be calculated18
by the single point method. The overall association constant
Ka for two DB24C8 macrocycles in equilibrium with 1-H2‚
2PF6 was found19 to be 7.4 × 106 M-2 in CD3CN/CD3NO2
(1:1) and 1.4 × 106 M-2 in CD3CN. The equilibrium
Acknowledgment. We thank the National Science Foun-
dation for their support of this research.
Supporting Information Available: Synthetic procedure
and relevant characterization data for 1-H2‚2PF6 and crystal
data for [(DB24C8)2‚1-H2][PF6]2. This material is available
free of charge via the Internet at http://pubs.acs.org.
+
constant, K1, for the binding of one DB24C8 to one NH2
center in the dication 1-H22+ was calculated to be 6200 M-1
in CD3CN/CD3NO2 (1:1) and 2800 M-1 in CD3CN. Likewise
K2, the equilibrium constant for the binding of a second
DB24C8 to the 1:1 complex, was found to be 1200 M-1 in
CD3CN/CD3NO2 (1:1) and 510 M-1 in CD3CN. The ∆G°
values arising from Ka, K1, and K2 (1:1 CD3CN/CD3NO2)
are -9.4, -5.2, and -4.2 kcal mol-1, respectively. The fact
that K1 for the formation of the [2]pseudorotaxane is over
OL006187G
(20) In a system where a substrate has two identical binding sites, K1 )
4K2 if the binding sites are independent. A system is positively cooperative
if K1/K2 is smaller than 4, noncooperative if equal to 4, and negatively
cooperative if greater than 4. See ref 12.
(21) Fyfe, M. C. T.; Stoddart, J. F.; Williams, D. J. Struct. Chem. 1999,
10, 243-259.
(18) Connors, K. A. Binding Constants; Wiley: New York, 1987.
(19) Association constants given for 1:1 DB24C8 and 1-H2‚2PF6
[CD3CN/CD3NO2 (1:1)] were obtained at concentrations of 7.0 and 3.5 mM,
respectively, while the Ka value given for CD3CN was an averaged value
for two different experiments, (a) 10 and 5 mM and (b) 20 and 10 mM in
DB24C8 and 1-H2‚2PF6, respectively. The overall association constant, Ka
) K1 × K2 where Ka ) [2:1]/([DB24C8][scaffold]), K1 ) [1:1]/([DB24C8]-
[scaffold]), and K2 ) [2:1]/([1:1][DB24C8]).
(22) For an example of an asymmetric monofunctionalized DB24C8
derivative that results in diastereoisomeric mixtures of complexes, see:
Ashton, P. R.; Baxter, I.; Cantrill, S. J.; Fyfe, M. C. T.; Glink, P. T.; Stoddart,
J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. 1998, 37,
1294-1297.
(23) See the following paper in this issue: Chang, T.; Heiss, A. M.;
Cantrill, S. J.; Fyfe, M. C. T.; Pease, A. R.; Rowan, S. J.; Stoddart, J. F.;
White, A. J. P.; Williams, D. J. Org. Lett. 2000, 2, 2947-2950.
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