Hydrogen-Bonded Molecular Shuttles
A R T I C L E S
positional isomer or co-conformation.6 In stimuli-responsive
molecular shuttles,7-11 an external trigger is used to chemically
modify the system and alter the noncovalent intercomponent
interactions such that the second macrocycle-binding site
becomes energetically more favored causing translocation of
the macrocycle along the thread to the second station (Figure
1). The system can be returned to its original state by using a
second chemical transformation to restore the initial order of
station binding affinities. Performed consecutively, these two
steps allow the ‘machine’ to carry out a complete cycle of
shuttling motion. The movement of the macrocycle from station
to station is thus caused by using chemical reactions to put the
molecule into nonequilibrium co-conformations and then al-
lowing the background thermal energy to drive the macrocycle
to the new global minimum (i.e., through biased Brownian
motion).
Figure 1. Translational submolecular motion in a stimuli-responsive
molecular shuttle: (i) the macrocycle initially resides on the preferred (green)
station; (ii) a reaction occurs (red f blue) changing the relative binding
potentials of the two stations such that (iii) the macrocycle ‘shuttles’ to the
now-preferred (blue) station. If the reverse reaction (blue f red) now occurs,
(iv) the components return to their original positions. The energy available
to do mechanical work through shuttling in such a cycle is the sum of the
difference in macrocycle binding energies of the two stations in each of
the two states (i.e., ∆∆Ggreen-red + ∆∆Gblue-green).
(5) For reviews on the development of interlocked molecules as molecular
machines, see: (a) Balzani, V.; Go´mez-Lo´pez, M.; Stoddart, J. F. Acc.
Chem. Res. 1998, 31, 405-414. (b) Sauvage, J.-P. Acc. Chem. Res. 1998,
31, 611-619. (c) Chambron, J.-C.; Sauvage, J.-P. Chem. Eur. J. 1998, 4,
1362-1366. (d) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart, J. F.
Angew. Chem., Int. Ed. 2000, 39, 3348-3391. (e) Asfari, Z.; Vicens, J. J.
Inclusion Phenom. Macro. Chem. 2000, 36, 103-118. (f) Pease, A. R.;
Jeppesen, J. O.; Stoddart, J. F.; Luo, Y.; Collier, C. P.; Heath, J. R. Acc.
Chem. Res. 2001, 34, 433-444. (g) Ballardini, R.; Balzani, V.; Credi, A.;
Gandolfi, M. T.; Venturi, M. Acc. Chem. Res. 2001, 34, 445-455. (h)
Collin, J.-P.; Dietrich-Buchecker, C.; Gavin˜a, P.; Jimenez-Molero, M. C.;
Sauvage, J.-P. Acc. Chem. Res. 2001, 34, 477-487. (i) Molecular Machines
and Motors: Structure and Bonding; Sauvage, J.-P., Ed.; Springer: Berlin,
2001;Vol. 99. (j) Venturi, M.; Credi, A.; Balzani, V. Molecular DeVices
and MachinessA Journey into the Nanoworld, Wiley-VCH: Weinheim,
2003.
(6) “Co-conformation” refers to the relative positions of the mechanically
interlocked components with respect to each other, see: Fyfe, M. C. T.;
Glink, P. T.; Menzer, S.; Stoddart, J. F.; White, A. J. P.; Williams, D. J.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2068-2070. Energy differences
between two translational isomers or co-conformations of greater than 1.18
kcal mol-1 imply >90% station occupancy for the more favored site at
298 K.
(7) For examples of chemically responsive molecular shuttles, see: (a) Lane,
A. S.; Leigh, D. A.; Murphy, A. J. Am. Chem. Soc. 1997, 119, 11092-
11093. (b) Mart´ınez-D´ıaz, M.-V.; Spencer, N.; Stoddart, J. F. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1904-1907. (c) Gong, C.; Gibson, H. W. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2331-2333. (d) Ashton, P. R.; Ballardini,
R.; Balzani, V.; Baxter, I.; Credi, A.; Fyfe, M. C. T.; Gandolfi, M. T.;
Go´mez-Lo´pez, M.; Mart´ınez-D´ıaz, M.-V.; Piersanti, A.; Spencer, N.;
Stoddart, J. F.; Venturi, M.; White, A. J. P.; Williams, D. J. J. Am. Chem.
Soc. 1998, 120, 11932-11942. (e) Jime´nez, M. C.; Dietrich-Buchecker,
C.; Sauvage, J.-P Angew. Chem., Int. Ed. 2000, 39, 3284-3287. (f) Lee, J.
W.; Kim, K.; Kim, K. Chem. Commun. 2001, 1042-1043. (g) Elizarov,
A. M.; Chiu, S.-H.; Stoddart, J. F. J. Org. Chem. 2002, 67, 9175-9181.
(h) Jimenez-Molero, M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P. Chem.
Eur. J. 2002, 8, 1456-1466. (i) Da Ross, T.; Guldi, D. M.; Farran Morales,
A.; Leigh, D. A.; Prato, M.; Turco, R. Org. Lett. 2003, 5, 689-691. (j)
Tseng, H.-R.; Vignon, S. A.; Stoddart, J. F. Angew. Chem., Int. Ed. 2003,
42, 1491-1495.
(8) For examples of photochemically responsive molecular shuttles, see: (a)
Benniston, A. C. Chem. Soc. ReV. 1996, 25, 427-435. (b) Murakami, H.;
Kawabuchi, A.; Kotoo, K.; Kunitake, M.; Nakashima, N. J. Am. Chem.
Soc. 1997, 119, 7605-7606. (c) Blanco, M.-J.; Jime´nez, M. C.; Chambron,
J.-C.; Heitz, V.; Linke, M.; Sauvage, J.-P Chem. Soc. ReV. 1999, 28, 293-
305. (d) Ashton, P. R.; Ballardini, R.; Balzani, V.; Credi, A.; Dress, K. R.;
Ishow, E.; Kleverlaan, C. J.; Kocian, O.; Preece, J. A.; Spencer, N.; Stoddart,
J. F.; Venturi, M.; Wenger, S. Chem. Eur. J. 2000, 6, 3558-3574. (e)
Wurpel, G. W. H.; Brouwer, A. M.; van Stokkum, I. H. M.; Farran, A.;
Leigh, D. A. J. Am. Chem. Soc. 2001, 123, 11327-11328. (f) Brouwer, A.
M.; Frochot, C.; Gatti, F. G.; Leigh, D. A.; Mottier, L.; Paolucci, F.; Roffia,
S.; Wurpel, G. W. H. Science 2001, 291, 2124-2128. (g) Stanier, C. A.;
Alderman, S. J.; Claridge, T. D. W.; Anderson, H. L. Angew. Chem., Int.
Ed. 2002, 41, 1769-1772. (h) Altieri, A.; Bottari, G.; Dehez, F.; Leigh,
D. A.; Wong, J. K. Y.; Zerbetto, F. Angew. Chem., Int. Ed. 2003, 42, in
press.
We recently reported the real-time observation of macrocycle
translocation in such a stimuli-responsive molecular shuttle
following the photochemically induced reduction of the naph-
thalimide unit in rotaxane 1.8f In fact, we originally designed 1
as an electrochemically switchable system.12 Electrochemistry
is potentially an attractive method through which to modulate
the behavior of molecular devices because it can be easily and
rapidly turned on and off while also offering a reagent and
waste-free procedure. Obviously, an important attribute of any
‘molecular machine’ is that for the submolecular motion to be
useful it must be detectable through some change in the system’s
(10) For examples of the use of electrical and electrochemical stimuli to control
ring rotation in catenanes, catenates, and rotaxanes, see: (a) Amabilino,
D. B.; Dietrich-Buchecker, C. O.; Livoreil, A.; Pe´rez-Garc´ıa, L.; Sauvage,
J.-P.; Stoddart, J. F. J. Am. Chem. Soc. 1996, 118, 3905-3913. (b) Ca´rdenas,
D. J.; Livoreil, A.; Sauvage, J.-P. J. Am. Chem. Soc. 1996, 118, 11980-
11981. (c) Livoreil, A.; Sauvage, J.-P.; Armaroli, N.; Balzani, V.; Flamigni,
L.; Ventura, B. J. Am. Chem. Soc. 1997, 119, 12114-12124. (d) Asakawa,
M.; Ashton, P. R.; Balzani, V.; Credi, A.; Hamers, C.; Mattersteig, G.;
Montalti, M.; Shipway, A. N.; Spencer, N.; Stoddart, J. F.; Tolley, M. S.;
Venturi, M.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. Engl.
1998, 37, 333-337. (e) Raehm, L.; Kern, J.-M.; Sauvage, J.-P. Chem. Eur.
J. 1999, 5, 3310-3317. (f) Collier, C. P.; Mattersteig, G.; Wong, E. W.;
Luo, Y.; Beverly, K.; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J.
R. Science 2000, 289, 1172-1175. (g) Asakawa, M.; Higuchi, M.;
Mattersteig, G.; Nakamura, T.; Pease, R.; Raymo, F. M.; Shimizu, T.;
Stoddart, J. F. AdV. Mater. 2000, 12, 1099-1102. (h) Bermudez, V.;
Capron, N.; Gase, T.; Gatti, F. G.; Kajzar, F.; Leigh, D. A.; Zerbetto, F.;
Zhang, S. Nature 2000, 406, 608-611. (i) Ashton, P. R.; Baldoni, V.;
Balzani, V.; Credi, A.; Hoffmann, H. D. A.; Mart´ınez-D´ıaz, M.-V.; Raymo,
F. M.; Stoddart, J. F.; Venturi, M. Chem. Eur. J. 2001, 7, 3482-3493.
(11) For examples of the use of electrochemical stimuli to control threading
and dethreading in pseudorotaxanes and other host-guest systems, see:
(a) Bernardo, A. R.; Stoddart, J. F.; Kaifer, A. E. J. Am. Chem. Soc. 1992,
114, 10624-10631. (b) Collin, J.-P.; Gavin˜a, P.; Sauvage, J.-P. Chem.
Commun. 1996, 2005-2006. (c) Asakawa, M.; Ashton, P. R.; Balzani, V.;
Credi, A.; Mattersteig, G.; Matthews, O. A.; Montalti, M.; Spencer, N.;
Stoddart, J. F.; Venturi, M. Chem. Eur. J. 1997, 3, 1992-1996. (d)
Devonport, W.; Blower, M. A.; Bryce, M. R.; Goldenberg, L. M. J. Org.
Chem. 1997, 62, 885-887. (e) Credi, A.; Montalti, M.; Balzani, V.;
Langford, S. J.; Raymo, F. M.; Stoddart, J. F. New. J. Chem. 1998, 22,
1061-1065. (f) Asakawa, M.; Ashton, P. R.; Balzani, V.; Boyd, S. E.;
Credi, A.; Mattersteig, G.; Menzer, S.; Montalti, M.; Raymo, F. M.; Ruffilli,
C.; Stoddart, J. F.; Venturi, M.; Williams, D. J. Eur. J. Org. Chem. 1999,
985-994. (g) Ashton, P. R.; Balzani, V.; Becher, J.; Credi, A.; Fyfe, M.
C. T.; Mattersteig, G.; Menzer, S.; Nielsen, M. B.; Raymo, F. M.; Stoddart,
J. F.; Venturi, M.; Williams, D. J. J. Am. Chem. Soc. 1999, 121, 3951-
3957. (h) Cooke, G.; Duclairoir, F. M. A.; Rotello, V. M.; Stoddart, J. F.
Tetrahedron Lett. 2000, 41, 8163-8166. (i) Balzani, V.; Credi, A.;
Mattersteig, G.; Matthews, O. A.; Raymo, F. M.; Stoddart, J. F.; Venturi,
M.; White, A. J. P.; Williams, D. J. J. Org. Chem. 2000, 65, 1924-1936.
(j) Balzani, V.; Becher, J.; Credi, A.; Nielsen, M. B.; Raymo, F. M.;
Stoddart, J. F.; Talarico, A. M.; Venturi, M. J. Org. Chem. 2000, 65, 1947-
1956. (k) Lahav, M.; Shipway, A. N.; Willner, I.; Nielsen, M. B.; Stoddart,
J. F. J. Electroanal. Chem. 2000, 482, 217-221.
(9) For examples of electrochemically responsive molecular shuttles, see ref
8a and the following: (a) Bissell, R. A.; Co´rdova, E.; Kaifer, A. E.; Stoddart,
J. F. Nature 1994, 369, 133-136. (b) Anelli, P.-L.; Asakawa, M.; Ashton,
P. R.; Bissell, R. A.; Clavier, G.; Go´rski, R.; Kaifer, A. E.; Langford, S.
J.; Mattersteig, G.; Menzer, S.; Philp, D.; Slawin, A. M. Z.; Spencer, N.;
Stoddart, J. F.; Tolley, M. S.; Williams, D. J. Chem. Eur. J. 1997, 3, 1113-
1135. (c) Collin, J.-P.; Gavin˜a, P.; Sauvage, J.-P. New J. Chem. 1997, 21,
525-528. (d) Armaroli, N.; Balzani, V.; Collin, J.-P.; Gavin˜a, P.; Sauvage,
J.-P.; Ventura, B. J. Am. Chem. Soc. 1999, 121, 4397-4408. (e) Ballardini,
R.; Balzani, V.; Dehaen, W.; Dell’Erba, A. E.; Raymo, F. M.; Stoddart, J.
F.; Venturi, M. Eur. J. Org. Chem. 2000, 591-602.
(12) Earlier attempts to make redox-active hydrogen-bonded molecular shuttles
based on anthraquinone subunits were unsuccessful (Dunnett, J. A. Ph.D.
Thesis, University of Manchester Institute of Science and Technology, U.K.,
2000).
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