A generic basis for some simple light-operated mechanical molecular machines

Article abstract of DOI:10.1021/ja0484193

A novel type of mechanical switch is described in which light-induced translation of a macrocycle in a [2]rotaxane quenches anthracene fluorescence. Features of the system include the remarkable 200:1 difference in fluorescence intensity between the two p

Full text of DOI:10.1021/ja0484193

Published on Web 09/11/2004
A Generic Basis for Some Simple Light-Operated Mechanical Molecular
Machines
Emilio M. Pe´rez,† David T. F. Dryden,† David A. Leigh,*,† Gilberto Teobaldi,‡ and
Francesco Zerbetto*,‡
School of Chemistry, UniVersity of Edinburgh, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK,
and Dipartimento di Chimica “G. Ciamician”, UniVersita` di Bologna, V. F. Selmi 2, 40126 Bologna, Italy
Received March 19, 2004; E-mail: David.Leigh@ed.ac.uk; Francesco.Zerbetto@unibo.it
The widespread utilization of submolecular motion in key bio-
logical processes is inspiring scientists to try to bridge the gap be-
tween synthetic chemical systems, which, by and large, rely upon
electronic and chemical effects and do not exploit molecular-level
motion (a notable exception being liquid crystals), and the macro-
scopic world, where our everyday machines rely upon the controlled
movement of multiple components to perform specific tasks. Most
efforts toward this goal have focused on establishing methods (for
example, the use of light) to control the positioning or movement
of submolecular fragments,1 but relatively little attention2 has been
given to what the effects of such motion might be. A bi-stable [2]-
rotaxane (a “molecular shuttle”) was recently described in which a
macrocycle could be moved with great positional integrity between
two well-separated binding sites in response to a photostimulus.3,4
Here we show how this large positional change can be used to
create a light-activated switch for fluorescence, exhibiting an
exceptional 200:1 on-off intensity ratio between the translational
states (∼85:1 between the photostationary state and the cis-isomer).5
We suggest that such “mechanical switching” could form the basis
for many different types of synthetic property-changing devices
and materials that, like biological systems, function through
mechanical motion at the molecular level (Figure 1).
Figure 1. Exploiting a well-defined, large-amplitude positional change to
trigger property changes. (i) A and B interact to produce a physical response
(fluorescence quenching, specific dipole or magnetic moment, NLO proper-
ties, color, creation/concealment of a binding site or reactive/catalytic group,
hydrophobic/hydrophilic region, etc.); (ii) moving A and B far apart mechan-
ically switches off the interaction and the corresponding property effect.
Scheme 1. Synthesis of Molecular Shuttle E/Z-1a
Molecular shuttle E/Z-1 (Scheme 1) has several key features:
A fumaramide-maleamide unit (dark blue-pink) provides a means
of changing the position of the macrocycle on the thread by altering
the binding affinity of one station for the macrocycle by several
kilocalories per mole using various olefin isomerization reactions
(photochemical, chemical, or thermal).3 A glycylglycine unit
(orange) offers a nonreactive station of intermediate binding affinity
between fumaramide and maleamide.2c The spacer between the
stations, here a C11 alkyl chain, can be chosen to suit the distance
dependency of the property one wishes to influence. Here we
illustrate the concept using fluorescence, introduced by attaching
a 9-carboxyanthracene residue (which is sufficiently bulky to also
act as a “stopper”) to the peptide station. The macrocycle contains
two pyridinium units, which are known to quench anthracene
fluorescence through electron transfer.6 Since electron transfer can
sometimes be remarkably efficient over long distances, we carried
out INDO/S calculations (see Supporting Information) to confirm
that the quenching should have the required high distance and
orientation dependency in E/Z-1.
a Reaction conditions: (i) potassium phthalimide, DMF, 80 °C, 16 h,
98%; (ii) NH2NH2‚H2O, EtOH, reflux, 1 h, then (Boc)2O, KOH, MeOH,
∼100%; (iii) 1-[3-dimethylaminopropyl]-3-ethylcarbodiimide hydrochloride
(EDCI), 4-(dimethylamino)pyridine (DMAP), CH2Cl2, 60%; (iv) trifluo-
roacetic acid (TFA), CH2Cl2; (v) EDCI, DMAP, CH2Cl2/DMF, (E)-3-(2,2-
diphenylethylcarbamoyl)acrylic acid 60%; (vi) 3,5-pyridinedicarbonyl
dichloride, p-xylylenediamine, Et3N, CHCl3, 48%; (vii) TFA, CH2Cl2; (viii)
312 nm, CH2Cl2, 20 min, 60%; (ix) 312 nm, CH2Cl2, 20 min, 40%, or
piperidine (3 equiv), CH2Cl2, rt, 16 h ∼100% or C2H2Cl4, 115 °C, 2 days,
90%. Z-2 is the cis-olefin isomer of E-2, its chemical structure is formally
provided in the SI.
Rotaxane E-1 was prepared in 48% yield from thread E-2 and
converted into Z-1 by photoisomerization (Scheme 1). The 1H NMR
of Z-1 in CDCl37 (Figure 2) confirms the location of the macrocycle
to be predominantly over the GlyGly residue. Hg and Hi are shielded
by 0.6 and 0.8 ppm with respect to their position in Z-2, and no
significant shifts are observed for Ho′ or Hp′. In contrast, in E-1 the
macrocycle resides overwhelmingly over the fumaramide station.
Ho and Hp are shifted 1.1 ppm upfield with respect to their positions
in the thread, while Hi and Hg occur at identical chemical shifts in
rotaxane and thread. The 1H NMR signal for HA and the significant
shifts in the pyridine signals compared to the free base rotaxanes
(see SI) confirm the protonation of the pyridine rings.
The photostationary state (PSS) of E-1/Z-1 (or E-2/Z-2) at 312
nm in CH2Cl2 is 40:60 (electronic absorption spectra are provided
† University of Edinburgh.
‡ Universita` di Bologna.
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J. AM. CHEM. SOC. 2004, 126, 12210-12211
10.1021/ja0484193 CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
decreases with this trend (opposite to the normally observed polarity
effects on electron transfer and excited-state relaxation processes)
as the macrocycle increasingly spends time away from the fumar-
amide station in positions within efficient quenching distance of
the anthracene. The exception, the reduced fluorescence intensity
of E-1 in CH2Cl2 compared to that in CH3CN and CH3OH, is
presumably a result of some H-bond-induced intramolecular folding.
The bi-stability and integrity of the macrocycle positioning in
CH2Cl2 means that starting with pure Z-1 (the “off” state) the system
can be written with light at 312 nm to give a photostationary E/Z-1
state which emits ∼85 times more light than the starting material
when addressed at a remote wavelength (λexc ) 365 nm).11 Once
written, it is essentially stable (T1/2 ≈ 24 h at 115 °C) unless treated
with piperidine. The most important feature of the system, however,
is that it demonstrates a principle which could be used to make
switches that can change any property that can be made to depend
on the spatial separation of submolecular fragments (Figure 1). The
use of stimuli-induced motion to bring individual components
together to perform specific tasks (e.g. electron transfer from one
part to another) which produce an effect (e.g., fluorescence
quenching), arguably makes such structures true mechanical mo-
lecular machines.
Figure 2. Partial 1H NMR spectra (400 MHz, CDCl3, 298 K) of (a) thread
Z-2, (b) [2]rotaxane Z-1 (HA δ ) 13.36 ppm), (c) thread E-2, and (d) [2]-
rotaxane E-1 (HA δ ) 13.45 ppm). All samples contained 2 equiv of CF3-
COOH. The assignments correspond to the lettering shown in Scheme 1.
Acknowledgment. This work was supported by the European
Union FET Program MechMol, the EPSRC, and the MURST project
“DispositiVi Supramolecolari”.
Supporting Information Available: Synthetic experimental pro-
cedures and INDO/S calculations. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) (a) Balzani, V.; Credi, A.; Raymo, F. M.; Stoddart J. F. Angew. Chem.,
Int. Ed. 2000, 39, 3348-3391. (b) Special issue on Molecular Machines:
Acc. Chem. Res. 2001, 34, 409-522.
(2) For systems where large-amplitude translational motion in a rotaxane
architecture brings about a property change, see: (a) size/shape variation
in a molecular “muscle”: Jimenez-Molero, M. C.; Dietrich-Buchecker,
C.; Sauvage, J.-P. Chem. Eur. J. 2002, 8, 1456-1466. (b) Changes in
conductivity: Collier, C. P.; Wong, E. W.; Beˇlohradsky´, M.; Raymo, F.
M.; Stoddart, J. F.; Kuekes, P. J.; Williams, R. S.; Heath, J. R. Science
1999, 285, 391-394. (c) Changes in circular dichroism: Bottari, G.; Leigh,
D. A.; Pe´rez, E. M. J. Am. Chem. Soc. 2003, 125, 13360-13361.
(3) (a) Altieri, A.; Bottari, G.; Dehez, F.; Leigh, D. A.; Wong, J. K. Y.;
Zerbetto, F. Angew. Chem., Int. Ed. 2003, 42, 2296-2300. (b) Bottari,
G.; Dehez, F.; Leigh, D. A.; Nash, P. J.; Pe´rez, E. M.; Wong, J. K. Y.;
Zerbetto, F. Angew. Chem., Int. Ed. 2003, 42, 5886-5889.
(4) For other light-switchable molecular shuttles, see: (a) Murakami, H.;
Kawabuchi, A.; Kotoo, K.; Kunitake, M.; Nakashima, N. J. Am. Chem.
Soc. 1997, 119, 7605-7606. (b) Armaroli, N.; Balzani, V.; Collin, J. P.;
Gavin˜a, P.; Sauvage, J. P.; Ventura, B. J. Am. Chem. Soc. 1999, 121,
4397-4408. (c) 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. (d) 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.
(e) Stanier, C. A.; Alderman, S. J.; Claridge, T. D. W.; Anderson, H. L.
Angew. Chem., Int. Ed. 2002, 41, 1769-1772.
Figure 3. (a) Fluorescence emission spectra (λexc ) 365 nm, 0.8 µM, 298
K) of E-1 (blue), Z-1 (pink), and the photostationary state (PSS, mauve).
The difference in fluorescence intensity between Z-1 and E-1 or the PSS is
clearly visible to the naked eye (inset: picture of the cuvettes under 365
nm UV light). (b) Fluorescence emission spectra (λexc ) 365 nm, 0.8 µM,
298 K) of E-1 (blue) and Z-1 (pink) in each of CH2Cl2, CH3CN, CH3OH,
and DMF. All the experiments were carried out after the addition of 2 equiv
of CF3COOH (TFA). Similar quenching and red-shifting was observed for
the bis(methylpyridinium tetrafluoroborate) analogue of Z-1 ((i) Z-1, MeI,
CH3CN, (ii) AgBF4). In the absence of TFA, E-1 and Z-1 exhibit
fluorescence spectra similar to those of the corresponding isophthalamide
macrocycle-based rotaxanes (i.e. nonquenched and, for Z-1, broadened and
red-shifted).4d In contrast, both threads (E/Z-2) have fluorescence spectra
indistinguishable from those of anthracene 9-carboxyamide and are unaf-
fected by the addition of TFA.
in the Supporting Information) and, starting from either isomer, is
reached within 20 min with no evidence of any decomposition.
Fluorescence spectra (λexc ) 365 nm) were obtained from 0.8
µM solutions of E-1 and Z-1 in CH2Cl2, CH3CN, CH3OH, and DMF
(Figure 3). A remarkable 200:1 intensity ratio between the trans
and cis shuttles (∼85:1 between Z-1 and the PSS) is observed for
the CH2Cl2 solutions at the maximum of E-1 emission (λmax ) 417
nm), Z-1’s fluorescence being almost completely quenched by the
pyridinium units and strongly red-shifted (Supporting Information)
by intercomponent hydrogen bonding of the anthracene carboxyam-
ide group to the macrocycle.4d,8,9 The emission spectra in the vari-
ous solvents show an increase in Z-1 luminescence with increasing
hydrogen bond basicity10 (CH2Cl2 < CH3CN < CH3OH < DMF),
consistent with a reduction in positional integrity of the macrocycle
at the GlyGly station as the intercomponent hydrogen bonds are
weakened. Conversely, the fluorescence intensity of E-1 generally
(5) For an example of a positionally switchable fluorescent pseudorotaxane,
see: Jun, S. I.; Lee, J. W.; Sakamoto, S.; Yamaguchi, K.; Kim, K.
Tetrahedron Lett. 2000, 41, 471-475.
(6) Clements, J. H.; Webber, S. E. Macromolecules 2004, 37, 1531-1536.
(7) The shift differences in CD2Cl2 are similar to those in CDCl3, but residual
CHDCl2 obscures part of the olefin region.
(8) Werner, T. C.; Rodgers, J. J. Photochem. 1986, 32, 59-68.
(9) Although Z-1 is shown in Scheme 1 with the macrocycle H-bonded to
the anthracenecarboxyamide group, this is actually only significant in the
excited state of the fluorophore. In the ground-state minimum energy co-
conformation it bridges the nonterminal amide group and the ester carbonyl
(see ref 4d and 1H NMR shifts of Hi and Hj in Figure 3, a and b)].
(10) (a) Marcus, Y. Chem. Soc. ReV. 1993, 22, 409-416. (b) Abraham, M. H.
Chem. Soc. ReV. 1993, 22, 73-83.
(11) After this manuscript was submitted, some fascinating light-switchable
shuttles were reported in which a small change in the position of a
cyclodextrin on a rotaxane thread changes the solvation sphere of a
fluorophore stopper sufficiently to alter the fluorescence intensity by a
ratio of ∼1.5:1 [Wang, Q.-C.; Qu, D.-H.; Ren, J.; Chen, K.; Tian, H.
Angew. Chem., Int. Ed. 2004, 43, 2661-2665].
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