Linear artificial molecular muscles

Article abstract of DOI:10.1021/ja051088p

Two switchable, palindromically constituted bistable [3]rotaxanes have been designed and synthesized with a pair of mechanically mobile rings encircling a single dumbbell. These designs are reminiscent of a "molecular muscle" for the purposes of amplifyin

Full text of DOI:10.1021/ja051088p

Published on Web 06/15/2005
Linear Artificial Molecular Muscles
Yi Liu,† Amar H. Flood,† Paul A. Bonvallet,†,| Scott A. Vignon,† Brian H. Northrop,†
Hsian-Rong Tseng,† Jan O. Jeppesen,# Tony J. Huang, Branden Brough,
Marko Baller,§ Sergei Magonov,§ Santiago D. Solares,‡ William A. Goddard,‡
Chih-Ming Ho,*, and J. Fraser Stoddart*,†
Contribution from the California NanoSystems Institute (CNSI), Department of Chemistry and
Biochemistry, Institute for Cell Mimetic Space Exploration (CMISE), and Mechanical and
Aerospace Engineering Department, UniVersity of California, Los Angeles, California 90095,
Department of Chemistry, UniVersity of Southern Denmark, Odense UniVersity, Denmark, Veeco
Instruments, 112 Robin Hills Road, Santa Barbara, California 93117, and Materials and
Process Simulation Center, DiVision of Chemistry and Chemical Engineering, California
Institute of Technology, Pasadena, California 91125
Received February 20, 2005; E-mail: chihming@ucla.edu; stoddart@chem.ucla.edu
Abstract: Two switchable, palindromically constituted bistable [3]rotaxanes have been designed and
synthesized with a pair of mechanically mobile rings encircling a single dumbbell. These designs are
reminiscent of a “molecular muscle” for the purposes of amplifying and harnessing molecular mechanical
motions. The location of the two cyclobis(paraquat-p-phenylene) (CBPQT4+) rings can be controlled to be
on either tetrathiafulvalene (TTF) or naphthalene (NP) stations, either chemically (1H NMR spectroscopy)
or electrochemically (cyclic voltammetry), such that switching of inter-ring distances from 4.2 to 1.4 nm
mimics the contraction and extension of skeletal muscle, albeit on a shorter length scale. Fast scan-rate
cyclic voltammetry at low temperatures reveals stepwise oxidations and movements of one-half of the
[3]rotaxane and then of the other, a process that appears to be concerted at room temperature. The active
form of the bistable [3]rotaxane bears disulfide tethers attached covalently to both of the CBPQT4+ ring
components for the purpose of its self-assembly onto a gold surface. An array of flexible microcantilever
beams, each coated on one side with a monolayer of 6 billion of the active bistable [3]rotaxane molecules,
undergoes controllable and reversible bending up and down when it is exposed to the synchronous addition
of aqueous chemical oxidants and reductants. The beam bending is correlated with flexing of the surface-
bound molecular muscles, whereas a monolayer of the dumbbell alone is inactive under the same conditions.
This observation supports the hypothesis that the cumulative nanoscale movements within surface-bound
“molecular muscles” can be harnessed to perform larger-scale mechanical work.
Introduction
tromechanical systems (NEMS). The most current investigations
have focused9 upon the transduction of chemical, electrical, or
As microscale electronic1 and mechanical devices2 continue
to be miniaturized, it has become clear that conventional “top-
down” lithographic techniques are not suited by themselves for
the fabrication of nanoscale components. Thus, a “bottom-up”
involvement,3 centered upon the design and manipulation of
molecular assembliessboth biological4,5 and artificial6-8shas
emerged as a potential tool for the development of nanoelec-
photochemical energy10 into controllable molecular motion and
hold potential for producing controllable nano- and mesoscale
mechanical systems driven by molecular machinery.11 A range
of hybrid nanomechanical systems, based upon phenomena such
as hydrogel swelling,12 the osmotic expansion of conjugated
polymers,13 motions associated with molecular recognition in
a supramolecular polymer system,14 ion intercalation in nano-
† The California NanoSystems Institute and Department of Chemistry
and Biochemistry, University of California, Los Angeles.
| Present address: Department of Chemistry, The College of Wooster,
Wooster, OH 44691.
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J. J.; Bachand, G. D.; Rizk, S. S.; Looger, L. L.; Hellinga, H. W.;
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# University of Southern Denmark, Odense University.
The Institute for Cell Mimetic Space Exploration (CMISE) and
Mechanical and Aerospace Engineering Department, University of Cali-
fornia, Los Angeles.
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10.1021/ja051088p CCC: $30.25 © 2005 American Chemical Society
J. AM. CHEM. SOC. 2005, 127, 9745-9759
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A R T I C L E S
Liu et al.
particle films,15 surface stress changes resulting from DNA
hybridization,16 and the electromechanical expansion of carbon
nanotubes,17 have been successful in transferring molecular
phenomena into macroscopic-scale motion. These systems,
however, rely primarily upon the response of a bulk material,
rather than upon individual molecular behavior. Recent advances
in the molecular arena include a crown-annelated oligoth-
iophene,18 a thiophene-fused [8] annulene,19 a unidirectional
three-station [2]catenane,20 a series of unidirectional chiroptical
rotary switches,21 ion-triggered contraction/extension molecular
motions22 and an array of rotaxane-based molecular switches
and shuttles.9,23 Pioneering work in the development of linear
molecular muscles6,11g,24 has been investigated, based on com-
pounds prepared using transition metal-based templates for the
formation of two-component interlocked molecules in which
the design is bioinspired to display contraction and extension
movements. These molecular systems have been shown to
undergo actuation, albeit in an incoherent manner in a solution
environment, heralding their potential utilization6 in mechanical
applications including nano- and microrobots for medicine and
everyday-life pursuits. Although not insurmountable, the har-
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manner within an ordered mechanical setting is proving to be
much more challenging. The alignment of liquid crystals has
been effected25 over large distances by controllable chiroptical
switches to achieve a range of colors. Although the bending of
an AFM beam by photoisomerization of a polymer strand
containing a single pendant azobenzene has been demonstrated26
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stringent demands of processability, cooperativity, addressability,
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9746 J. AM. CHEM. SOC. VOL. 127, NO. 27, 2005

Linear Artificial Molecular Muscles
A R T I C L E S
To date, the most complete and efficient forms of molecular
machinery come, not from the laboratory, but from the biological
world, e.g., the rotary motion of F0F1-ATPase, which has been
extensively investigated.5,27,28 In another example, the sarcomere,
the cellular unit in the contraction of natural skeletal muscle, is
composed primarily of alternately stacked filaments of the
globular proteins actin and myosin.29 During muscle contraction,
the myosin and actin filaments slide relative to each other as
the result of a powerful stroke within each of the many pendant
myosin heads.30 This movement, which is reminiscent of a
rowing action and is powered chemically through the hydrolysis
of ATP, suggests that a biomimetic approach6,8 to the design
of artificial molecular machinery may lie in the incorporation
of linear, mutually sliding components that can undergo
contraction and extension in response to a chemical stimulus.
In the realm of artificial molecular machinery,11 motor-
molecules, such as bistable catenanes and bistable rotaxanes,31
are particularly well-suited for nanomechanical work on account
of their structural composition and ease of addressability. Most
notable, however, is the fact that their mutually interlocked
components can usually undergo controllable movements (Fig-
ure 1). The redox-active tetrathiafulvalene (TTF) unit serves32
as an excellent recognition site for the tetracationic cyclophane,
cyclobis(paraquat-para-phenylene) (CBPQT4+), as a result of
electron donor and acceptor (π-π stacking) interactions. In an
unperturbed bistable [2]rotaxane,23b the CBPQT4+ ring possesses
a dramatically greater affinity for the TTF unit than for the
competing naphthalene (NP) ring system. Upon one- or two-
electron oxidation of the TTF unit, the CBPQT4+ ring is
electrostatically repelled and moves immediately to the NP
station.23b,c The Coulombic repulsion of the TTF2+ unit, coupled
with the π-donor ability of the NP station, provides a powerful
“push-pull” mechanism for the translocation of the CBPQT4+
ring within the rotaxane’s dumbbell component. Chemical or
electrochemical reduction of the TTF2+ unit back to its neutral
state allows the ring to return to its original thermodynamically
Figure 1. Structural formulas of the bistable [2]rotaxane motif that forms
the basis for the design of a palindromic [3]rotaxane.
favored position23b,c by a thermally activated diffusive process.
The bistable nature and the “all-or-nothing” switching behavior
(i.e., only one of the translational isomers is significantly
populated) of rotaxanes and catenanes have provided the basis
for several molecular electronic devices.33 The switches,
however, have yet to be harnessed in the mechanical sense for
the performing of molecular-scale work. The mechanical
sequence of “power stroke” and recovery step34 in rotaxane
switching resembles the cooperative and progressive cycle of
force production in natural biological machinery, thus inviting
concept transfer35 from the life sciences into materials science
during the design of a rotaxane-based molecular muscle.
Building upon knowledge gained23,36 in the design, syn-
thesis, and operation of bistable [2]rotaxanes, a prototypical
palindromic [3]rotaxane (molecular muscle) PPR‚8PF6 was
identified (Figure 2) in order to mimic the contraction and
extension motion of skeletal muscles. This rational design
incorporates two pairs of complementary TTF (green) and
NP (red) recognition stations arranged symmetrically along a
rod component which is encircled by two CBPQT4+ (blue) ring
components. It was decided to introduce a rigid spacer between
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Y.; Collier, C. P.; Heath, J. R. Acc. Chem. Res. 2001, 34, 433-444. (c)
Collier, C. P.; Jeppesen, J. O.; Luo, Y.; Perkins, J.; Wong, E. W.; Heath,
J. R.; Stoddart, J. F. J. Am. Chem. Soc. 2001, 123, 12632-12641. (d) Luo,
Y.; Collier, P.; Jeppesen, J. O.; Nielsen, K. A.; DeIonno, E.; Ho, G.; Perkins,
J.; Tseng, H.-R.; Yamamoto, T.; Stoddart, J. F.; Heath, J. R. ChemPhysChem
2002, 3, 519-525. (e) Diehl, M. R.; Steuerman, D. W.; Tseng, H.-R.;
Vignon, S. A.; Star, A.; Celestre, P. C.; Stoddart, J. F.; Heath, J. R.
ChemPhysChem 2003, 4, 1335-1339. (f) Steuerman, D. W.; Tseng, H.-
R.; Peters, A. J.; Flood, A. H.; Jeppesen, J. O.; Nielsen, K. A.; Stoddart, J.
F.; Heath, J. R. Angew. Chem., Int. Ed. 2004, 43, 6486-6491. (g) Flood,
A. H.; Peters, A. J.; Vignon, S. A.; Steuerman, D. W.; Tseng, H.-R.; Kang,
S.; Heath, J. R.; Stoddart, J. F. Chem. Eur. J. 2004, 10, 6558-6564. (h)
Flood, A. H.; Stoddart, J. F.; Steuerman, D. W.; Heath, J. R. Science 2004,
306, 2055-2056. (i) Mendes, P. M.; Flood, A. H.; Stoddart, J. F. Appl.
Phys. A 2005, 80, 1197-1209.
(29) Spudich, J. A.; Rock, R. S. Nature Cell Biol. 2002, 4, E8-E10.
(30) Geeves, M. A. Nature 2002, 415, 129-131.
(31) For a representative selection of monographs and reviews on catenanes
and rotaxanes, see: (a) Schill, G. Catenanes, Rotaxanes and Knots;
Academic: New York, 1971. (b) Amabilino, D. B.; Stoddart, J. F. Chem.
ReV. 1995, 95, 2725-2828. (c) Vo¨gtle, F.; Dunnwald, T.; Schmidt, T. Acc.
Chem. Res. 1996, 29, 451-460. (d) Breault, G. A.; Hunter, C. A.; Mayers,
P. C. Tetrahedron 1999, 55, 5265-5293. (e) Hubin, T. J.; Kolchinski, A.
G.; Vance, A. L.; Busch, D. H. AdV. Supramol. Chem. 1999, 5, 237-357.
(f) Sauvage, J.-P.; Dietrich-Buchecker, C., Eds. Molecular Catenanes,
Rotaxanes and Knots; VCH-Wiley: Weinheim, 1999. (g) Raehm, L.;
Hamilton, D. G.; Sanders, J. K. M. Synlett 2002, 1743-1761.
(34) A power stroke is an activation-less process, and the results of ongoing
studies are not able to distinguish between whether or not the electrostati-
cally driven movement is barrier-less.
(35) Glink, P. T.; Stoddart, J. F. Pure Appl. Chem. 1998, 70, 419-424.
(36) (a) Bissell, R. A.; Co´rdova, E.; Kaifer, A. E.; Stoddart, J. F. Nature 1994,
369, 133-137. (b) Jeppesen, J. O.; Perkins, J.; Becher, J.; Stoddart, J. F.
Angew. Chem., Int. Ed. 2001, 40, 1216-1221. (c) Jeppesen, J. O.; Nielsen,
K. A.; Perkins, J.; Vignon, S. A.; Di Fabio, A.; Ballardini, R.; Gandolfi,
M. T.; Venturi, M.; Balzani, V.; Becher, J.; Stoddart, J. F. Chem. Eur. J.
2003, 9, 2982-3007. (d) Yamamoto, T.; Tseng, H.-R.; Stoddart, J. F.;
Balzani, V.; Credi, A.; Marchioni, F.; Venturi, M. Collect. Czech. Chem.
Commun. 2003, 68, 1488-1514. (e) Kang, S.; Vignon, S. A.; Tseng, H.-
R.; Stoddart, J. F. Chem. Eur. J. 2004, 10, 2555-2564.
(32) (a) Philp, D.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.; Williams, D.
J. Chem. Commun. 1991, 1584-1586. (b) 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. (c) 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. (d) Nielsen, M. B.; Jeppesen, J. O.; Lau, J.;
Lomholt, C.; Damgaard, D.; Jacobsen, J. P.; Becher, J.; Stoddart, J. F. J.
Org. Chem. 2001, 66, 3559-3563.
9
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A R T I C L E S
Liu et al.
Figure 2. (a) Graphical representations of the constitution and cycle of contraction and extension of the sarcomeres that form basic element of movement
in skeletal muscle. (b) Structural formulas of the contracted (PPR8+) and the extended (PPR12+) states of the prototypical molecular muscle. The distances
between the adjacent recognition unit is around 1.4 nm.
the two NP stations with a distance37 of about 1.4 nm as a
compromise between the rigidity of the backbone, while
retaining flexible di(ethylene glycol) chains for maintaining38
enhanced yields for the template-directed synthesis of the
rotaxane. In common with the parent (Figure 1) two-station [2]-
rotaxanes, the location of the CBPQT4+ rings can be activated
to switch between TTF stations and NP stations as a function
of the TTF stations’ redox state. Provided that the molecule is
fully stretched, the distance between the CBPQT4+ rings can
be varied from between ca. 4.2 to ca. 1.4 nm apart. This inter-
ring distance change of ca. 2.8 nm represents a dramatic
mechanical strain of 67%. By contrast, a linear strain of 12%
was recently reported for a conducting polymer actuator,13 and
the maximum twitch sarcomere shortening in natural skeletal
muscle is39 ca. 8%. The [3]rotaxane TPR.8PF6 was designed
(Figure 3) to incorporate a disulfide tether on each of the
CBPQT4+ ring components. The introduction of the tethers
provides an anchoring point by which the [3]rotaxane molecules
can be attached to a gold surface, allowing the transduction of
redox-driven mechanical movements of those molecules to
impose strain on the underlying solid substrate. As the movable
rings are Coulombically driven to different locations along the
dumbbell, the strain generated by the molecular motions is
expected to be transduced to the bound substrate.
(37) A fragment of PPR8+, constrained to its fully elongated conformation, was
minimized with the AMBER* (Assisted Model Building and Energy
Refinement) force field and GB/SA (Generalized Born/Surface Area)
solvent model for CHCl3 as implemented in Maestro 3.0.038 module of
the Schro¨dinger molecular modeling suite.
(38) The stabilizing C-H‚‚‚O interactions between the diethylene glycol oxygen
atoms and the R-bipyridinium hydrogen atoms greatly enhance the yield
of the clipping reaction, see, for example, (a) Brown, C. L.; Philp, D.;
Stoddart, J. F. Synlett 1991, 462-464. (b) Asakawa, M.; Dehaen, W.;
L′abbe´, G.; Menzer, S.; Nouwen, J.; Raymo, F. M.; Stoddart, J. F.; Williams,
D. J. J. Org. Chem. 1996, 61, 9591-9595. (c) Castro, R.; Nixo, K. R.;
Evanseck, J. D.; Kaifer, A. E. J. Org. Chem. 1996, 61, 7298-7303. (d)
Houk, K. N.; Menzer, S.; Newton, S. P.; Raymo, F. M.; Stoddart, J. F.;
Williams, D. J. J. Am. Chem. Soc. 1999, 121, 1479-1487. (e) Raymo, F.
M.; Bartberger, M. D.; Houk, K. N.; Stoddart, J. F. J. Am. Chem. Soc.
2001, 123, 9264-9267.
In a recent communication,7 we described the operation of a
NEMS device in which TPR8+ becomes self-assembled to the
gold surface on an array of microcantilever beams of dimension
(39) Mutungi, G.; Ranatunga, K. W. J. Muscle Res. Cell Motil. 2000, 21, 565-
575.
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Linear Artificial Molecular Muscles
A R T I C L E S
Figure 3. Structural formula and graphical representation of a disulfide-tethered molecular muscle TPR8+
.
Scheme 1. Synthesis of the Dumbbell-Shaped Compounds 11 and TPD
500 × 100 × 1 µm with a spring constant of 0.02 N m-1
.
necessary control studies that verify the active role that the flex-
ing of the molecular muscle plays in bending the cantilever beams.
Cantilever arrays were utilized on account of their design for
optimal flexibility, which is one reason they are being utilized
for sensors40a and as microcalorimeters.40b The deflection of a
cantilever is sensitive not only to temperature, pH, electrostatic
charges, and photothermal effects but also to chemical factors
such as protein-ligand binding and DNA hybridization.16 In
the latter example, control studies are critical for identifying
the cause of the effect. In this context, we performed the
In this full paper, we describe (i) the synthesis (Scheme 1)
of a prototypical palindromic molecular muscle PPR.8PF6, a
disulfide-tethered molecular muscle TPR.8PF6, and a control
dumbbell-shaped component TPD and (ii) the spectroscopic
characterization of the redox-controllable biomimetic contrac-
tion-extension mechanical movement of the molecular muscles
in solution, with respect to chemical or electrochemical stimulus.
Finally, we return to the mechanism of force production in the
molecular muscles and consider the details of how the chemo-
mechanical transduction of nanometer movements causes a
micron-scale cantilever to bend controllably.
(40) (a) Baller, M. K.; Lang, H. P.; Fritz, J.; Gerber, C.; Gimzewski, J. K.;
Drechsler, U.; Rothuizen, H.; Despont, M.; Vettiger, P.; Battiston, F. M.;
Ramseyer, J. P.; Fornaro, P.; Meyer, E.; Guntherodt, H. J. Ultramicroscopy
2000, 82, 1-9. (b) Berger, R.; Gerber, C.; Gimzewski, J. K.; Meyer, E.;
Guntherodt, H. J. Appl. Phys. Lett. 1996, 69, 40-42.
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A R T I C L E S
Liu et al.
Scheme 2. Synthesis of the Prototype Palindromic [3]Rotaxane PPR.8PF6 and a [2]Rotaxane 15.4PF6
[3]rotaxane TPR.8PF6 was prepared, after stirring a mixture of
PPD, the disulfide-containing bis(hexafluorophosphate) salt
22.2PF6, 1,4-bis(bromomethyl)benzene (14), and NH4PF6 in
DMF for 7 days. Ultrahigh-pressure conditions (12 kbar) were
employed in order to increase the yield of the [3]rotaxane. The
[3]rotaxane TPR.8PF6 and [2]rotaxane 23.4PF6 were separated
by column chromatography on SiO2 and isolated as green solids
in yields of 10% and 14%, respectively.
Results and Discussion
Synthesis. The routes employed in the synthesis of the [3]-
rotaxanes PPR.8PF6 and TPR.8PF6, and the control dumbbell-
shaped compound TPD are outlined in Schemes 1-3. Reaction
(Scheme 1) of the TTF-containing tosylate 1 and 2,6-diisopro-
pylphenol (2) or 4-hydroxy-3,5-diisopropyl-benzaldehyde (3)41
in the presence of K2CO3 afforded, respectively, the alcohols 4
and 5, which were tosylated subsequently to give 6 and 7. The
synthesis of the rigid dinaphthol 10 was achieved by a
Sonogashira coupling42 between 1,4-diacetylenebenzene (8) and
the iodide43 9 in 85% yield. Reaction of the dinaphthol 10 and
2.2 equiv of the tosylate 6 or 7 in the presence of K2CO3
afforded the dumbbell-shaped compound 11 (PPD) or 12. The
dialdehyde 12 was further reduced to a diol, followed by its
esterification (DCC/DMAP/CH2Cl2) with thioctic acid, to give
the disulfide-tethered dumbbell-shaped compound TPD. The
prototypical palindromic [3]rotaxane PPR.8PF6 and a [2]-
rotaxane 15.4PF6 were separated (Scheme 2) after stirring a
mixture of PPD, the bis(hexafluorophosphate) salt44 13.2PF6,
1,4-bis(bromomethyl)benzene (14) and NH4PF6 in DMF under
ambient conditions, followed by preparative thin-layer chro-
matography (PTLC) on SiO2 using Me2CO/NH4PF6 (1.0 g NH4-
PF6 in 100 mL Me2CO) as the eluent.
Structural Characterization of [3]- and [2]Rotaxanes by
1H NMR Spectroscopy and Mass Spectrometry. The 1H NMR
spectrum (CD3COCD3/298 K) of the [3]rotaxane PPR.8PF6
revealed (Figure 4a) two pairs of signals of equal intensities at
δ ) 6.25 and 6.30 ppm, and at δ ) 6.33 and 6.38 ppm,
respectively, which correspond to the TTF protons in the units,
cis- and trans-isomers.23b A 1:2 integration ratio between the
signals of the dumbbell and the CBPQT4+ ring indicates that,
for each dumbbell component, there are two encircling CB-
PQT4+ rings in keeping with the molecular structure of a [3]-
rotaxane. For the [2]rotaxane 15.4PF6, integration between the
dumbbell signals and the CBPQT4+ signals gives a ratio of 1:1,
indicating that only one ring encircles the dumbbell component.
In both cases, no resonancessthat could be ascribed to encircled
NP ring protonsswere observed, clearly suggesting close to an
“all-or-nothing” equilibrium. Electrospray ionization mass spec-
trometry (ESI-MS) unambiguously distinguishes the [3]rotax-
anes from the corresponding [2]rotaxanes. The mass spectrum
of [3]rotaxane PPR.8PF6 reveals46 (Table 1) a singly charged
peak at m/z values 1742.4 ([M - 2PF6]2+), together with doubly
Scheme 3 outlines the preparation of the active disulfide-
tethered [3]rotaxane TPR.8PF6. The dibromide45 16 underwent
esterification (DCC/DMAP/CH2Cl2) with ethylene glycol (17)
to give the alcohol 18 in 33% yield. Refluxing a mixture of 18
and 4,4′-bipyridine (19) in MeCN afforded the dicationic salt
20.2PF6, after counterion exchange (NH4PF6/H2O). Compound
22.2PF6 was obtained in a yield of 98% by esterification of
20.2PF6 with thioctic acid (21). The active disulfide-tethered
and triply charged peaks at m/z values 1113.3 ([M - 3PF6]3+
)
and 798.7 ([M - 4PF6]4+), an observation which corresponds
to the consecutive loss of two, three and four hexafluorophos-
phate ions (mol. wt. ) 145 Da each), and a molecular mass of
3774.8. In comparison, the mass spectrum of the [2]rotaxane
15.4PF6 reveals peaks at m/z values 1192.4, 746.6 and 523.7,
corresponding to the mass of [M - 2PF6]2+, [M - 3PF6]3+ and
(41) Roth, B.; Baccanari, D. P.; Sigel, C. W.; Hubbell, J. P.; Eaddy, J.; Kao, J.
C.; Grace, M. E.; Rauckman, B. S. J. Med. Chem. 1988, 31, 122-129.
(42) Taylor, R. J. K., Ed. Organocopper Reagents; IRL Press: Oxford, 1994.
(43) Ishii, H., Harada, Y.; Asaka, T.; Murakami, Y.; Honaoka, T.; Ikeda, N.
Yakugaku Zasshi 1976, 96, 1259-1264.
(44) Stoddart, J. F. et al. J. Am. Chem. Soc. 1992, 114, 193-218.
(45) Stoddart, J. F. et al. Chem. Eur. J. 1997, 3, 152-169.
(46) Molecular weight and m/z values apply to the lowest mass component of
any isotope distribution and are based on a scale in which 12C ) 12.000.
9
9750 J. AM. CHEM. SOC. VOL. 127, NO. 27, 2005

Linear Artificial Molecular Muscles
A R T I C L E S
Scheme 3. Synthesis of a Disulfide-Tethered [3]Rotaxane TPR.8PF6 and a [2]Rotaxane 23.4PF6
[M - 4PF6]4+ (M ) 2674.8). The mass difference between the
two compounds is 1100.0, corresponding to the mass of one
CBPQT4+ ring component. Similarly, the mass spectra of the
active disulfide-tethered [3]rotaxane TPR.8PF6 and [2]rotaxane
23.4PF6 reveal (Table 1) the consecutive loss of up to five
hexafluorophosphate ions and a mass difference of one disulfide-
tethered CBPQT4+ ring component between their molecular
weights.
tions with the para-phenylene bridges in the CBPQT4+ rings
resonate upfield (Figure 5) at δ ) 2.95 and 2.88 ppm. Other
peaks, corresponding to NP protons, resonate (Figures 4 and 5)
at δ ) 7.39, 6.41, 6.35, and 6.02. Examination of the 1H DQF-
COSY (double quantum filtered correlation spectroscopy)
spectrum for the oxidized [3]rotaxane shows clearly the scalar
coupling between the protons of the NP stations. Addition of
Zn powder to the CD3COCD3 solution, followed by vigorous
shaking, leads to reduction of the TTF2+ dications back to their
neutral state and the consequent shuttling back of the CBPQT4+
Chemical Switching of the Palindromic [3]Rotaxane
1
1
Monitored by H NMR Spectroscopy. A series of H NMR
spectroscopic experiments were performed to reveal the precise
nature23b of the redox-controllable switching process undergone
by the [3]rotaxane PPR‚8PF6. After recording the spectrum
(Figure 4a) of a solution of PPR‚8PF6 in CD3COCD3 at 233
K, 4.6 equiv of the one-electron oxidant, tri(p-bromophenyl)-
amminium hexafluoroantimonate, was added and the sample
was cooled back down immediately47 to 233 K. Examination
of the spectrum (Figure 4b) for the oxidized sample provides
evidence for complete oxidation of both TTF units to their bis-
oxidized forms, i.e., PPR8+ is oxidized to PPR12+. The two
peaks, corresponding to the dicationic TTF2+ units, can be
identified at δ ) 9.42 and 9.41 ppm. As a result of the
deshielding effect of these aromatic units, the signals corre-
sponding to the adjacent CH2 groups are moved downfield away
from the CH2O signals and can be observed at δ ) 5.38 and
5.34 ppm. Evidence for movement of the CBPQT4+ rings from
the TTF unit to the NP ring systems is apparent from the
observation of upfield shifts of the peaks corresponding to the
protons of the NP stations. Dramatically, the H-4/8 protons of
the encircled NP sitesswhich participate in C-H‚‚‚π interac-
1
rings from the NP stations to the TTF ones. The original H
NMR spectrum is restored (Figure 4c) in all its glory!
Electrochemical Switching Monitored by CV and UV/Vis
Spectroelectrochemistry. The redox-controlled contraction and
extension of the inter-ring distance in the bistable [3]rotaxane
PPR8+ has been investigated using cyclic voltammetry (CV)
and UV-visible spectroelectrochemistry. In the presence of two
mechanically mobile CBPQT4+ rings, it is important to under-
stand how the mechanism of electromechanical switching is
coupled to the sequence of TTF-based oxidations. In particular,
do the two CBPQT4+ rings move in a stepwise or in concerted
manner? To answer this question, CVs were recorded at different
scan rates and at two temperaturessroom temperature and -25
°Csin order to time-resolve the mechanical switching. In
addition, slow scan-rate CV, in conjunction with controlled-
potential UV-visible spectroelectrochemistry, was employed48
to detect any changes in the switching mechanism that occur at
slow switching speeds. The bistable [2]rotaxane 154+ was48
investigated in order to identify whether the presence of an
additional unpopulated station influences its switching perfor-
(47) It is necessary to keep the sample at low temperature to increase the stability
over the time period necessary to collect the 2D spectra.
(48) Liu, Y.; Flood, A. H.; Moscowitz, R. M.; Stoddart, J. F. Chem. Eur. J.
2004, 10, 369-385.
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A R T I C L E S
Liu et al.
Figure 4. 1H NMR spectra of (a) PPR8+ at room temperature, (b) bis-oxidized PPR12+ at 243 K, and (c) reduced PPR8+ at room temperature. All spectra
were recorded in CD3COCD3 at 500 MHz. The green box highlights peaks from TTF protons and the red box indicates peaks of three of the “inside” NP
protons.
Table 1. The ESI-MS Characterizationa of [2]- and [3]Rotaxanes
PPD, as well as a disubstituted diethylene glycol TTF compound
(TTF thread) and the CBPQT4+ cyclophane were utilized as
no. of
-
lost PF6
counterions
PPR.8PF6
MW 3774.8
15.4PF6
MW 2674.8
TPR.8PF6
MW 4326.8
23.4PF6
MW 2950.6
mechanically inactive control systems.
)
)
)
)
The redox-mediated mechanical switching of PPR8+ and the
corresponding dumbbell PPD were characterized using CV
(Figure 6) at fast scan rates. The oxidative region of the CV of
PPR8+ displays (Figure 6a) a single anodic peak at +800 mV
and two cathodic reduction peaks at +700 and +400 mV. This
CV profile is qualitatively similar to those that have been
obtained for bistable [2]catenanes and [2]rotaxanes.32c,49 Con-
sequently, the first process can be assigned to the formation of
the two TTF2+ dications, concomitant with the mechanical
movements of the CBPQT4+ rings to the two NP ring systems.
The cathodic peaks on the return sweep can be assigned to the
stepwise reductions of the dications to the monocations TTF+•
and subsequently the neutral TTF. By contrast, the dumbbell
component PPD displays (Figure 6d) two well-separated
processes, corresponding to the oxidations of both TTF units
at the same potentials. The TTF-based oxidation processes lie
at E1/2(PPD)2+/0 ) +350 mV and E1/2(PPD)4+/2+ ) +800 mV,
respectively, and the two-electron oxidation product is more
stable in CH2Cl2 than in MeCN by comparison with the CV of
the TTF thread. The reduction region of the CV of PPR8+
displays two processes with cathodic peaks at approximately
-400 and -800 mV. Each redox process can be assigned by
analogy (Figure 6c) to the free CBPQT4+ cyclophane. Conse-
quently, the first process corresponds32c to the reduction of the
two CBPQT4+ rings, and expresses itself in two closely spaced
peaks. The first is revealed as a weak shoulder at -355 mV,
occurring at the same potential as that (-357 mV) of the free
cyclophane while the second process is shifted by 100 mV to
more negative potentials (-452 mV). The splitting has previ-
2
3
4
5
1742.4 (18%) 1192.4 (32%) 2018.4 (55%) 1330.3 (30%)
1113.3 (100%) 746.6 (97%) 1297.3 (87%) 838.6 (100%)
523.7 (100%) 936.8 (100%) 592.7 (21%)
720.4 (22%)
798.7 (16%)
-
-
-
a Data are presented as m/z ratio and (relative abundance). Molecular
weight and m/z values apply to the lowest mass component of any isotope
distribution and are based on a scale in which 12C ) 12.000.
Figure 5. 2D DQF-COSY of the bis-oxidized PPR12+, showing the
correlation between the NP proton resonances. The H4/8 protons of NP
ring system resonate at very high field δ ) 3.20 and 3.15 ppm, indicating
the location of the NP ring system inside the CBPQT4+ macrocycle.
mance or if it behaves, somewhat trivially, as a linear combina-
tion of the dumbbell-like moiety plus that of the [2]rotaxane-
like other half. For both rotaxanes, the dumbbell compound
(49) Flood, A. H.; Peters, A. J.; Vignon, S. A.; Steuerman, D. W.; Tseng, H.-
R.; Kang, S.; Heath, J. R.; Stoddart, J. F., Chem. Eur. J. 2004, 24, 6558-
6561.
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Linear Artificial Molecular Muscles
A R T I C L E S
(+1050 mV), the reduction peaks are only half their expected
intensities, consistent with oxidation occurring in only one-half
of the rotaxane. Moreover, the reduction peak at 700 mV,
assigned to the dication, can only be present if the dication is
formed after the first of the two oxidation processes.
In addition, the second cycle of the fast-scan rate CV at 248
K reveals a small peak at 570 mV that is assigned to a small
proportion (<5%) of the switched metastable state49 remaining
after 0.9 s. Consequently, the movement of the ring back to the
TTF unit is estimated to relax over a free energy barrier of less
than 14 kcal mol-1. Attempts to erase51 the metastable state by
reducing the CBPQT4+ rings at ∼-400 mV during the CV cycle
were effective for the singly switched half but not when both
sides are oxidatively switched. A full quantitative analysis of
the metastable state in solution was not possible with such low
barriers.
The bistable [2]rotaxane 154+ displays (Figure 6b) a complex
CV that is, quite simply, a linear combination of half of the
[3]rotaxane PPR8+ and the dumbbell PPD. The oxidation region
of the CV displays a redox couple of the bare dumbbell-like
TTF unit (oxidation and reduction, E1/2 ) +340 mV) that is
achieved at a similar potential to that of the dumbbell. The
second oxidation peak at +760 mV corresponds to the peak
observed for the [3]rotaxane PPR8+, and it can be assigned to
a three-electron process in which two electrons are removed
from the encircled TTF unit and one from the bare monocation
TTF+•. The reduction process at +675 mV corresponds closely
to that noted for PPR8+ and can be assigned to the reformation
the monocationic TTF+• units at both ends of the rotaxane. The
peak at +410 mV can be assigned to the reduction of the TTF+•
monocation back to its neutral form, producing a metastable
state at one end of the [2]rotaxane that is in a dynamic
equilibrium with the ground state. The reduction of the
CBPQT4+ ring is similar to that observed for both the [3]-
rotaxane PPR8+ and the free CBPQT4+ cyclophane. However,
the fully reduced state 150 appears to become precipitated onto
the electrode.
Figure 6. Cyclic voltammetry of the (a) molecular muscle PPR8+, and its
precursor compounds in the form of (b) [2]rotaxane 154+, (c) CBPQT4+
,
(d) PPD, and (e) the TTF thread. The data have been scaled for ease of
comparison of the CVs and the scale bars at 0.0 V correspond to 5 µA. All
data presented was recorded at 200 mV s-1 in argon purged MeCN except
for PPD (CH2Cl2), 1.0-0.5 × 10-3 mol L-1, 0.1 M TBAPF6, room
temperature, glassy carbon working electrode (0.0178 cm2).
ously been taken44,50 to imply that the two bipyridinium subunits
in a single CBPQT4+ ring are no longer chemically equivalent.
However, in the bistable [3]rotaxane PPR8+, another interpreta-
tion is possiblesnamely, that the two CBPQT4+ rings reside in
different chemical environments. It is significant that the shapes
of the two anodic reoxidation processes are both tall and thin.
This behavior is more pronounced at slower scan rates of around
10 mV s-1 and more or less absent at fast scan rates in the
region of 1000 mV s-1 and is assigned to precipitation of the
reduced forms on the electrode surface.
The CVs of PPR8+ recorded (Figure 7) at 248 K by contrast
to the room temperature studies reveal, not only a stepwise
mechanism for the cyclophanes’ movements following oxidation
of the TTF units, but also the presence of a metastable state. At
1000 mV s-1, two broad overlapping peaks are observed at 900
and 1150 mV, when the scan direction of the CV is switched
back at a vertex potential of +1500 mV. Moreover, the
characteristic reduction peaks, observed during the cathodic
sweep, indicate the return of the dication in a standard fashion,
first to the monocation and then subsequently back to the neutral
form. The first of the oxidation peaks can be assigned to
oxidation and movement of a single CBPQT4+ ring on only
one-half of the [3]rotaxane and the second peak to the same
process in the other half of the rotaxane. When the CV is
switched at a vertex potential halfway between the two peaks
UV/Visible Spectroelectrochemistry. The UV-visible spec-
troscopic changes (Figure 8) associated with the electrochemical
oxidation processes of PPR8+ were recorded in order to identify
the mechanical location of the CBPQT4+ cyclophanes, as well
as the mechanism of switching. The observed changes are
compared to those of the dumbbell PPD in order to identify
these changes that are solely associated with the mechanically
mobile cyclophanes. The ground-state UV-visible spectrum of
PPR8+ displays (Figure 8a) the characteristic52 charge-transfer
band at 850 nm assigned to the TTF f CBPQT4+ electronic
transition. Upon oxidation over the potential range 650-730
mV employing a controlled-potential protocol, the ground-state
bands bleach and are replaced by characteristic bands in the
visible region at 600 and 450 nm that signify the formation of
the two monocations, TTF+•. Concomitant with the changes in
the visible region, the UV band at 360 nm, assigned to a π-π*
transition of the conjugated naphthalene phenylenevinylene core,
is observed to red-shift and to lose some of its intensity. These
(51) Tseng, H. R.; Wu, D.; Fang, N.; Zhang, X.; Stoddart, J. F. ChemPhysChem
2004, 5, 111-116.
(52) 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.
1998, 37, 333-337.
(50) Asakawa, M.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Belohradsky, M.;
Gandolfi, M. T.; Kocian, O.; Prodi, L.; Raymo, F. M.; Stoddart, J. F.;
Venturi, M. J. Am. Chem. Soc. 1997, 119, 302-310.
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A R T I C L E S
Liu et al.
Figure 7. Cyclic voltammetry of the molecular muscle PPR8+ recorded at a low temperature (248 K) and at a fast scan rate (1000 mV s-1) with two
different vertex potentials. The inset shows a small peak at 570 mV has grow-in for the second cycle of the CV.
changes indicate that the π-π* transition is sensitive to the
movement of the two rings to encircle the NP rings systems.
After holding the potential at 730 mV until all the spectroscopic
changes have stopped, a second oxidation process is initiated a
mere 10 mV after the first process has ended. The spectra display
a bleaching of the TTF+• bands with formation of a shoulder at
∼380 nm characteristic with the formation of the TTF2+
dication. Bleaching the TTF+• chromophore reveals a weak band
at 520 nm, which is assigned to the NP f CBPQT4+ CT
electronic transition. Moreover, the weakened and red-shifted
UV band assigned to the rigid NP-based core of the dumbbell
does not alter. Both of these observations indicate that the
CBPQT4+ cyclophanes have relocated to the NP ring systems
and that their movements occurred after the initial formation
of the TTF+• monocations.
By comparison, the dumbbell-only component, PPD, displays
(Figure 9) much simpler spectroscopic changes that occur at
well-separated oxidation potentials. The spectroscopic changes
were recorded at the beginning of 60 mV windows during a
slow scan rate (0.5 mV s-1) CV in an optically transparent thin-
layer electrochemical cell. The thin layer CV displays (inset to
Figure 9) the same features as the solution CV. The first
oxidation process generates the TTF+• state, PPD2•/2+, evidenced
by the visible bands at 450 and 600 nm. There are no changes
observed in the UV band of the rigid core at 360 nm that were
otherwise observed for the [3]rotaxane. The second oxidation
is verified by the bleach in the visible region and growth of the
shoulder at 400 nm with a weak shoulder revealed at 440 nm.
The spectrum is flat at 510 nm attesting to the absence of the
mechanically mobile CBPQT4+ cyclophanes. The returning
cathodic sweep of the CV through the two reductions generates
spectroscopic changes that are virtual facsimiles of those
observed throughout the anodic sweep. In a separate experiment
that utilizes a controlled-potential protocol, the spectroscopic
changes of PPD were the same as those observed using the
slow scan-rate CV protocol (Figure 9). It is noteworthy that
the first oxidation of PPD (400-500 mV) recorded in the
controlled-potential experiment is well-separated by 350 mV
from the second oxidation (850-1000 mV) by comparison to
PPR8+, which exhibits almost no separation (10 mV) at all.
This difference indicates that the presence of the tetracationic
rings significantly alter the oxidation potentials of the TTF units
and is a spectroelectrochemical observation that is consistent
with the CV.
The spectroelectrochemistry of the [2]rotaxane 154+ was
recorded throughout the single cycle of a CV (0.5 mV s-1).
The linear combination of the dumbbell and rotaxane halves
observed in the solution-phase CV is represented (Figure 10,
insets) in the thin-layer CV with concomitant spectroscopic
changes. The distinct (Figure 10a) TTF-based oxidation of the
dumbbell end, observed at +400 mV, is followed in the UV-
visible spectrum by a bleach at 300 nm and the growth of the
monocation based visible bands, although the 850 nm CT band
is completely unaltered. Subsequently, a shoulder in the CV at
700 mV is unambiguously assigned to the mono-oxidation of
the rotaxane end by the UV-visible changes; i.e., the 850 nm
CT band is finally bleached and (Figure 10b) the TTF+•
chromophore doubles in its intensity from 0.25 to 0.50. The
oxidation to the dicationic form occurs simultaneously (Figure
10c) at each end of the [2]rotaxane producing only a weak NP
f CBPQT4+ band at 510 nm assigned to the single CT
chromophore. The anodic return to the monocation is a reverse
of the dications’ formation. The rotaxane end is reformed at
550 mV although the spectroscopic changes are not so well
resolved from those of the dumbbell end at 350 mV. It is noted
that the CV of the thin-layer spectrolectrochemical cell corre-
sponds to that CV recorded in bulk solution with a scan rate of
8 mV s-1, indicating the usefulness of the spectroelectrochemical
technique for assigning features in the CV.
In summary, the solution-phase CV and the spectroscopic
changes following the oxidation and reduction cycle of the [3]-
rotaxane, its dumbbell and the [2]rotaxane are self-consistent
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Linear Artificial Molecular Muscles
A R T I C L E S
Figure 8. UV-visible spectroelectrochemistry of PPR8+ (∼0.3 × 10-3
mol L-1, MeCN, 0.1 mol L-1 TBAPF6) recorded over a range of potentials
in order to resolve (a) the formation of the TTF-based monocationic and
switched form (650-730 mV) and then (b) the formation of the corre-
sponding dicationic forms (>730 mV). The chromophoric components
responsible for each absorption are marked.
Figure 9. UV-visible spectroelectrochemistry of the dumbbell PPD (∼1
× 10-3 mol L-1, CH2Cl2, 0.1 mol L-1 TBAPF6) recorded simultaneously
with a CV (inset, 0.2 mV s-1) showing the corresponding growth and bleach
of the related chromophores. The voltage ranges that account for the
spectroscopic changes are marked on the CV in bold and correspond to the
formation of TTF-based (a) monocations PPD2•/2+ and (b) dications PPD4+
together with the reverse reformation of (c) the monocations and (d) neutral
forms.
and attest to the movement of the cyclophane(s) following
oxidation of the TTF unit(s). For PPR8+, the spectroelectro-
chemistry confirms the movement of the cyclophanes after the
first oxidation, and for 154+, the assignment of each of the
oxidation redox processes were unambiguously distinguished.
In addition, the mechanism of mechanical switching of the
molecular muscle can be changed (Scheme 4) from concerted
at ambient temperatures to one that operates in a stepwise
manner at cryogenic temperatures.
Mechanical Actuation of Cantilever Arrays Using Mo-
lecular Muscles. The reversible chemical switching of PPR8+
in solution provided a basis for the design (Figure 11a) of a
chemomechanical actuator7 utilizing the linear molecular muscle
TPR8+ self-assembled by Au-S bonds onto cantilever beams.
The oxidation-induced contraction of the inter-ring distance
generated a tensile stress that was transduced to the underlying
substrate through the tethers. The resulting cumulative effect
of a randomly oriented ensemble of 6 billion molecular muscles
in a SAM on the cantilever beam, produced an upward
mechanical bending of the beam. Subsequently, reduction-
induced extension of the inter-ring distance in TPR8+ was
observed to relieve the stress upon the beam, thus resulting in
a downward motion and a return to the beam’s original
equilibrium position.
Briefly, a silicon cantilever array coated on its topside with
a 20 nm thin layer of gold was coated2 with the muscle
molecules and placed in the transparent fluid cell of a Digital
Instruments Scentris Research Tool modified for the deflection
experiments. No attempt was made to align the molecules in
the monolayer, thus determining that only the component of
the contraction that is aligned with the long axis of the cantilever
contributes effectively to the beam’s bending. Aqueous Fe-
(ClO4)3 (oxidant) and ascorbic acid (reductant) solutions were
sequentially and alternatively introduced into the fluid cell under
constant flow (250-300 µL/min). The deflection of the beams
versus time (Figure 11) indicate that synchronous with addition
of the oxidant solution (1.0 mM), all four cantilever beams
(Figure 10b, only one beam deflection is shown) bend upward
by ca. 35 nm to an apparent saturation point in 1 min.
Introduction of the reductant solution (2.0 mM) caused the
cantilever beams to bend back downward to their starting
positions. In the original study, a number of the alternative
factors that could lead to synchronous deflection were dis-
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A R T I C L E S
Liu et al.
Figure 10. UV-visible spectroelectrochemistry of the [2]rotaxane 154+ (∼0.3 × 10-3 mol L-1, MeCN, 0.1 mol L-1 TBAPF6) recorded simultaneously
with a CV (inset, 0.2 mV s-1) showing the corresponding growth and bleach of the related chromophores. The voltage ranges that account for the spectroscopic
changes are marked on the CV in bold and correspond to the stepwise formation of the TTF-based (a) monocation of the dumbbell-like end 15•/3+ of the
[2]rotaxane and the (b) monocationic and switched form of the rotaxane-like end 152•/2+ followed by formation of the (c) dicationic form at both ends 154+
.
counted.7 A control compound TPD bearing disulfide tethers
at either end was tested under identical conditions (Figure 11c)
and revealed that changes in the electrostatic charge, confor-
mational rearrangements, and thermal effects do not bend the
beams. pH Changes were found to contribute insignificantly
using an experimental setup with the molecular muscle. Pho-
tothermal effects would be insignificant with such small laser
beam diameters (∼3 µm). In any event, these alternative factors
would more likely bend the beam downward in marked contrast
to what is observed.
The binary bending behavior was observed for 25 cycles with
a noticeable decrease of the magnitude of the beam bending.
This effect may be attributed to one or a combination of gradual
chemical and/or physical passivation of the SAM including
chemical degradation of the molecular muscle, movement of
individual gold atoms, and/or the S-Au attachment sites by
virtue of the dynamic self-assembly process.53 Nevertheless, the
movement of the cantilever beams is directly correlated with
the cycling of the oxidant and reductant solutions. While it may
be possible for any number of the heretofore unobserved (yet
reversible) molecular conformational rearrangements to take
place within the molecules or within the monolayer’s structure,
the simplest explanation lies with the collective effect of
molecular-scale contraction and extension of the inter-ring dis-
tance in the [3]rotaxanes. This result suggests that the cumulative
effect of individual molecular-scale motions within disulfide-
tethered [3]rotaxane molecules, even when randomly aligned,
can be harnessed to perform larger-scale mechanical work.
To gain a more quantitative understanding of the chemo-
mechanical transduction and amplification process, the beams’
deflection was analyzed based on the molecular force generated
from the contraction of the molecular muscle. The mean
molecular force of each individual TTF2+/CBPQT4+ interaction
can be calculated based on Coulomb’s law
(53) Ulman, A. An Introduction to Ultrathin Organic Films From Langmuir-
Blodgett to Self-Assembly; Academic Press: San Diego, 1991.
F ) q1q2/4πꢀ0ꢀr2
(1)
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Linear Artificial Molecular Muscles
A R T I C L E S
Scheme 4. Electrochemically-Stimulated Switching Cycle from Extended to Contracted Forms of PPR8+ under Normal Conditions as Well
as at Slow and Fast Switching Speeds (superscripts on the square brackets relate to intermediates (I) and metastable states (MS))
where F is the instantaneous electrostatic force that exists
between two charges, q1 (+2) and q2 (+4), that are a distance
r apart from each other within a surrounding medium of
dielectric ꢀ (80, H2O) and where ꢀ0 is the permittivity of free
space. One-half of the rotaxane system was modeled by placing
(Figure 12a) four positive charges distributed evenly on a ring
with two positive charges located at the ring’s center. The total
force and its x-component (Fx) aligned along the dumbbell was
calculated as a function of the distance along the dumbbell.
to water (ꢀ ) 80). Any specific ion pairing is assumed to be
-
negligible, given the aqueous solubilities of the ClO4 coun-
terions that will be present in exchange10e for the PF6- anions.
On balance, while the tetracationic rings come within 1.4 nm
Fx ) F × x/r
(2)
where
r2 ) x2 × R2
(3)
in which x is the distance along the dumbbell and R is the radius
of the tetracationic ring. The rotaxane in an idealized linear
conformation of the dumbbell can be considered as an upper
limit for the force that can be produced in a single molecular
muscle. The maximum mean force Fm was determined by
integrating the area under the force curve (Fx) from 0 to 1.4
nm and then dividing this value by the distance that the ring
moves, 1.4 nm. As a means to consider how the force would
change if the dumbbell component of the molecular muscle
begins in a folded state on account of side-on interactions with
the NP stations and favorable H-bonding with the intervening
diethylene glycol spacer, a second minimum-force scenario was
evaluated (Figure 12). In this case, the oxidized, surface-bound
compound TPR12+ is expected to be linear to reduce any
Coulombic repulsion. This transformation is akin to the net
movement of the ring from its origin toward the NP site by 0.6
nm (equivalent to twice the π-π stacking distance) coupled
with a movement of the TTF2+ unit 0.8 nm away from the
origin. Consequently, the final linear conformational arrange-
ment of the molecular muscle is used to approximate the
minimum mean force by integrating the area under the curve
from 1.4 to 0.8 nm. Finally, the dielectric constant for the
aqueous solution is assumed to remain unaffected54 on the
addition of 1-2 mM of the redox reagent and thus equivalent
Figure 11. (a) Schematic diagram of the proposed mechanism of the
device’s operation. Experimental data showing (b) 25 cycles of the upward
and downward bending of one cantilever beam coated with TPR8+ and (c)
the limited deflection of the cantilever array coated with the control dumbbell
compound TPD under alternative oxidation and reduction conditions. The
red and green arrows indicate the time when oxidant or reductant solution
is injected into the fluidic cell. A negative deflection corresponds to an
upward bending of the cantilever beams.
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A R T I C L E S
Liu et al.
of 50 and 34 nm, respectively, which is in good agreement with
the experimental result (35 nm).
Alternatively, from the force constant of the cantilever and
the measured deflection, the force per molecule can be estimated
(Supporting Information), based on simple geometrical assump-
tions and continuum calculations related to Hooke’s law. Given
a deflection of 35 nm, the force per molecule is 10.2 pN. This
value is in the order of magnitude of the force calculated as a
result of electrostatic interactions within each molecular muscle,
although smaller in magnitude. This observation is reasonable
since, in this analysis, the tension is assumed to be uniformly
distributed on the top surface of the cantilever. This assumption
is not strictly true since tension only occurs between the anchors
of the two rings, so that the forces required of each surface-
bound [3]rotaxane is greater than what has been calculated.
These calculations reveal that the top surface of the beam
shortens by 0.14 nm corresponding to an average compression
of 0.001 pm per molecule between the anchoring points of the
rings.
Given that the time required for the beams to bend is
attributed to mixing within the solution, it is difficult to analyze
the mechanistic details of the molecular muscle’s contraction
and extension. Nevertheless, one could consider a number of
possible scenarios. Primarily, the rings move in order to
minimize Coulombic forces (push). They are believed to move
toward the NP donor stations because (1) they can bind with
the NP stations (pull), a situation that will additionally (2)
mediate the four positive charges on each ring on account of
favorable charge-transfer mixing. This inter-ring contraction is
counterbalanced by the cantilever’s spring constant and thus
the movements of the individual rings in molecular muscles
may well occur in an stepwise fashion, one ring first and then
the other, in a thermally activated process until each molecular
movement is complete. Beyond such considerations about the
mechanism of the chemomechanical transduction, it remains
unambiguous that the surface-bound mechanically mobile rings
are essential for the beam’s bending.
Figure 12. The electrostatic force produced from one end of the rotaxane
can be estimated on the basis of (a) a simple model describing the geometry
and charges present from which can be derived and (b) a graph that describes
how the total and x-component force changes depending on the distance
between the tetracationic ring (4+) and the origin of the TTF2+ charges.
(c) The maximum and minimum force can be estimated from the two
reasonable extremes of the surface-bound molecular muscle’s conformation.
In the maximum, the rings move the largest distance, whereas for the
minimum-force case, the rings close up only a little while the dumbbell
becomes elongated.
Conclusions
Artificial molecular motors, based on a palindromic [3]-
rotaxane constitution, have been constructed and shown sub-
sequently to display a unique biomimicry of natural muscles.
1H NMR spectroscopic and UV-visible spectroelectrochemical
experiments show clearly that the voltage-addressable oxidation/
reduction cycle of the TTF unit can control precisely the
locations of the two ring components of a palindromic [3]-
rotaxane along its dumbbell-shaped component. At normal
electrochemical stimulation speeds, the extended inter-ring state
becomes contracted when each TTF unit is dicationic. At slower
stimulation speeds, the monocationic forms can be identified.
At low temperatures and faster speeds, the two rings move
stepwise from their respective ends of the rotaxane and the
metastable state relaxes much faster than 10 s-1 at 248 K. The
ring movements under redox conditions provide an optimal
change of 2.8 nm in terms of the inter-ring distance, representing
a strain of 67% with respect to the original inter-ring distance.
The ability to control the movement of the rings between the
two switched states in response to external stimuli makes this
molecule an excellent candidate for constructing a molecular
device. Disulfide tethers attached to the rings enable the
of each other, the 1H NMR spectroscopic study (Figure 4, 233
K) reveals that they have >95% occupancy on the NP sites.
These two scenarios for the mean molecular force determine
the maximum and minimum values of 21 and 14 pN from which
it is possible to calculate theoretically how much the cantilever
beam of the dimension (500 × 100 × 1 µm) and spring constant
(0.02 N m-1) should bend when it is covered completely by 6
billion molecular muscles that are randomly aligned yet all
switching simultaneously. A mechanical analysis, akin to the
analysis of stresses and strains in plate tectonics,55 reveals7 that
the collective effect of the generated molecular forces can
generate a bending moment, which will result in an out-of-plane
beam displacement with a maximum and minimum magnitude
(54) Hubbard, J. B.; Onsager, L.; Vanbeek, W. M.; Mandel, M. Proc. Natl.
Acad. Sci. U.S.A. 1977, 74, 401-404.
(55) Turcotte, D. L.; Schubert, G. Geodynamics; Cambridge University Press:
Cambridge, 2002.
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Linear Artificial Molecular Muscles
A R T I C L E S
anchoring of molecular motors to solid substrates. By formation
of a SAM on the gold surface of an array of microcantilever
beams, the molecular motors are incorporated into a NEMS
device that undergoes controllable and reversible bending as
they are subjected to chemical oxidants and reductants. Control
studies indicate that it is the contraction and extension of the
surface-bound nanoscale molecular muscles that lead to the
bending of a beam that is five orders of magnitude larger in
size. A logical developmentsby replacing the chemically driven
redox process with direct electrical or optical stimulationswould
contribute to a technological basis for the production of a new
class of multi-scale NEMS devices based upon nanomechanical
motion in switchable interlocked molecules.
NASA’s Institute for Cell Mimetic Space Exploration, and by
the Defense Advanced Research Projects Agency (DARPA)
Biomolecular Motors program. Some of the compound char-
acterizations are supported by the National Science Foundation
under equipment grant numbers CHE-9974928 and CHE-
0092036. In Denmark, this work was supported by the Danish
Natural Science Research Council (SNF, grants 21-03-0014 and
21-03-0317).
Supporting Information Available: Syntheses of all com-
pounds. Detailed analysis of cantilever bending mechanics based
on Hooke’s law. Complete refs 44 and 45. This material is
available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was funded in part by a
National Science Foundation NIRT grant (ECS-0103559), by
JA051088P
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