Remarkable positional discrimination in bistable light- and heat-switchable hydrogen-bonded molecular shuttles

Article abstract of DOI:10.1002/anie.200250745

A tale of two stations: Molecular shuttles, in which a macrocyclic unit can move between two stations over a relatively large distance (1.5 nm), exhibit bistability that can be induced using either light or heat as stimuli, and exhibit large required vari

Full text of DOI:10.1002/anie.200250745

Communications
Bistable Molecular Shuttles
Remarkable Positional Discrimination in Bistable
Light- and Heat-Switchable Hydrogen-Bonded
Molecular Shuttles**
Andrea Altieri, Giovanni Bottari, Francois Dehez,
David A. Leigh,* Jenny K. Y. Wong, and
Francesco Zerbetto*
Stimuli-responsive molecular “shuttles”[1–11] (that is, mechan-
ically interlocked molecules in which a macrocycle can be
translocated between different sites in response to an external
signal) all operate through the same basic principle. The
external stimulus does not intrinsically induce directional
motion of the macrocycle. Rather, it alters the equilibrium
between different translational co-conformers by increasing
the binding strength of the less populated station and/or
destabilizing the initially preferred binding site. The motion
of the components arises from the background thermal
energy, the net result being a change in the position of the
macrocycle through biased Brownian motion (Figure 1).
Given this mode of action, a major problem in designing
photoactive shuttles that can function as practical compo-
nents for molecular machinery is finding ways of generating
sufficiently large, long lived, binding-energy differences
between pairs of positional isomers.[2–10] A Boltzmann dis-
tribution at 298 K requires a value of DDG between transla-
tional co-conformers of approximately 2 kcalmolꢀ1 for 95%
occupancy of one station. Achieving such discrimination in
two states to form a positionally bistable shuttle (that is, both
DDGorange-blue and DDGorange-green ꢁ 2 kcalmolꢀ1) by modifying
only intrinsically weak, noncovalent binding modes, without
adding external reagents, presents a significant challenge. The
problem has previously been overcome, in part, by using
photochemistry to block the position of the macrocycle in
single-binding-site rotaxanes.[5,10] In these systems the macro-
cycle is only able to sit on an azobenzene[5] or stilbene unit[10]
in the E diastereomer of the rotaxane and must reside
elsewhere in the Z form. Unfortunately, the integrity of
macrocycle positioning in such systems is likely to be limited
[*] Prof. D. A. Leigh, A. Altieri, Dr. G. Bottari, Dr. J. K. Y. Wong
School of Chemistry, University of Edinburgh
The King's Buildings, West Mains Road, Edinburgh EH9 3JJ (UK)
Fax: (+44)131-667-9085
E-mail: David.Leigh@ed.ac.uk
Prof. F. Zerbetto, Dr. F. Dehez
Dipartimento di Chimica “G. Ciamician”
Università degli Studi di Bologna
via F. Selmi 2, 40126 Bologna (Italy)
Fax: (+39)051-2099456
E-mail: gatto@ciam.unibo.it
[**] This work was supported bythe European Union Future and
Emerging TechnologyProgramme MechMol, the EPSRC and the
MURST project “Dispositivi Supramolecolari”. D.A.L. is an EPSRC
Advanced Research Fellow (AF/982324)
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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DOI: 10.1002/anie.200250745
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¼
hydrogen-bonding interactions (NH···O C bond lengths,
angles etc.; Figure 2) including: the hydrogen-bond basicity
of the functional groups (amides are superior to esters[13]),
preorganization (fumaramide is superior to succinamide[17]),
and distance between the binding sites (succinamide is
superior to adipamide[18]).
Some features of the synthetic routes to 1–3 are note-
worthy. Although E-1 was prepared from the corresponding
trans-olefin-containing E-5 (an “E thread”) in good yield, the
other E threads could not be utilized owing to their insuffi-
cient solubility in solvents that do not disrupt hydrogen
bonding. Rotaxanes Z-2 and Z-3 were therefore prepared
from the corresponding Z-threads and converted to the
E rotaxanes thermally (1208C, 1–7 days, C2H2Cl4, 80–95%).
In fact, the E isomers of each molecular shuttle could be
converted to the Z forms with light (E!Z, direct irradiation
at 254 nm, CH2Cl2, 30 min, 39–54%; or with a catalytic
benzophenone sensitizer at 350 nm, CH2Cl2, 5 min, 60–65%)
and back again through heating or reversible Michael
addition (catalytic ethylenediamine, 608C, 4 h, 75–85%).
Since the xylylene rings of the macrocycle shield encap-
sulated regions of the thread, the position of the macrocycle in
Figure 1. Macrocycle translation in a stimuli-responsive molecular
shuttle. Stimulus A induces a blue-to-green transformation, and stimu-
lus B induces a green-to-blue transformation. The equilibrium distribu-
tion of the macrocycle between two stations is determined by the
difference in their binding energies (DDGorange-blue, DDGorange-green) and
the temperature.
unless the thread is very short. Here we describe photo-
and thermally responsive shuttles (1–3) in which the
macrocycle moves over
a relatively large distance
(approximately 1.5 nm) between two discrete stations
with remarkable positional integrity (even at room
temperature), despite the fact that the discrimination
between the binding sites is caused only by “matched” and
“mismatched” hydrogen-bonding motifs. Each transla-
tional form is stable until a new stimulus is applied.
The basis for the new shuttles lies in the photo-
chemical and thermal interconversion of fumaramide and
maleamide groups.[12] The trans-olefin bisamide acts as an
excellent template for the formation of benzylic amide
macrocycle-based rotaxanes (for example, E-4; Figure 2)
because the amide carbonyl groups of the thread are
rigidly held in positions that fit the hydrogen-bond-
donating sites of the forming macrocycle (an arrangement
maintained even in crystals of E-4 obtained from DMSO;
Figure 2a).[13] Irradiation of fumaramide rotaxanes at
254 nm[14] produces the corresponding cis-maleamide
rotaxane, in which the maximum number of intercompo-
nent hydrogen bonds changes from four to two (Fig-
ure 2b), considerably reducing the binding strength[15]
between the macrocycle and the thread. By incorporating
a second binding site into the thread, we reasoned it might
be possible to generate photoinduced, thermally rever-
sible translation of the rotaxane components.
Figure 2. X-raystructures of model single-binding-site [2]rotaxanes showing hydrogen-
bonding characteristics of predicted “strong” (a), “weak” (b), and “intermediate
strength” (c–e) hydrogen-bonding stations; a) fumaramide rotaxane E-4 crystallized
from DMSO; b) N,N’-dimethyl derivative of the corresponding maleamide (Z) rotax-
ane; c) succinamide analogue of E-4; d) adipamide analogue of E-4; e) succinic
amide ester analogue of E-4. Intramolecular hydrogen-bond lengths [Š] (and angles
[8]): a) O40-HN2/O40A-HN2A 2.13 (173.7); O40-HN11/O40A-HN11A 1.89 (169.3);
b) O40-HN11 2.08 (139.3); O43-HN2 2.00 (142.1); c) O40-HN2/O43-HN20 1.88
(165.3); d) O40-HN2/O45-HN28 2.00 (168.8); e) O40-HN11/O43-HN29 1.89 (156.1).
Atoms: carbon (macrocycle), blue; carbon (thread), yellow; oxygen, red; nitrogen,
dark blue; amide hydrogen, white. In all cases, the rotaxane “stoppers” are
We prepared three different molecular shuttles (1–3;
Scheme 1), each containing a fumaramide/maleamide site
plus a non-photoactive second station with a predicted
intermediate macrocycle-binding affinity. Since the tran-
sition state of the rotaxane-forming reaction is similar in
structure to the final rotaxane,[16] it seemed likely that the
macrocycle-binding affinity of a given station should be
related to its ability to template the formation of the
rotaxane. Several factors are known to affect both
template efficacy and the nature of the intercomponent -CH2CHPh2 groups.
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Scheme 1. Synthesis of bistable molecular shuttles 1–3. a) Succinic anhydride, Et3N, CH2Cl2, 90%; b) H2N(CH2)12NHBoc, 4-dimethylaminopyridine
(DMAP), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDCI·HCl), CH2Cl2, 68%; c) trifluoroacetic acid, CHCl3, quantitative;
d) fumaric acid monoethylester, DMAP, EDCI·HCl, CH2Cl2, 85%; e) NaOH in H2O, EtOH, 91%; f) DMAP, EDCI·HCl, DMF, E-5, 76%; g) isophtha-
loyl dichloride, p-xylylenediamine, Et3N, CHCl3, E-1, 57%; h) hn at 254 nm for 30 min, CH2Cl2, Z-1, 54%; Z-2, 48%; Z-3, 39%, or hn at 350 nm for
5 min, benzophenone, CH2Cl2, Z-1, 65%; Z-2, 65%; Z-3, 60%; i) C2H2Cl4 at 1208C for 7 days, E-1, 80%; E-2, 80%; or 1 day, E-3, 95%; j) maleic
anhydride, anhydrous THF, 75%; k) succinic anhydride, anhydrous THF, 95%; l) SOCl2, 1,12-diaminododecane, CH2Cl2, 35%; m) adipic acid mon-
oethylester, DMAP, EDCI·HCl, CH2Cl2, 86%; n) KOH in H2O, EtOH, 95%; o) H2N(CH2)12NHBoc, DMAP, EDCI·HCl, CHCl3, 92%; p) trifluoroacetic
acid, CHCl3, quantitative; q) DMAP, EDCI.HCl, CHCl3, Z-5, 70%; Z-6, 70%; Z-7, 70%; r) isophthaloyl dichloride, p-xylylenediamine, Et3N, CHCl3,
Z-1, 2%; Z-2, 40%; Z-3, 20%. Boc=tert-butoxycarbonyl. Full experimental procedures can be found in the Supporting Information.[25]
CDCl3 could be determined for each pair of rotaxane
diastereomers by comparing the chemical shift of the protons
in the rotaxane with those of the corresponding thread (or
suitable model compounds in the case of E-2 and E-3).[19] The
spectra of E/Z-1 and E/Z-5 in CDCl3 (400 MHz, 298 K) are
shown in Figures 3 and 4. The Hi and Hj protons of the
fumaramide group are shielded in the rotaxane E-1, com-
pared to the thread E-5, by d = 1.09 and 1.02 ppm, whereas
the chemical shifts of the Hc and Hd protons of the succinic
amide ester group are similar in both compounds (Figure 3).
In the maleamide isomer, the situation is completely reversed
(Figure 4). The Z olefin protons (Hi’ and Hj’) resonate at
almost identical chemical shifts in the rotaxane and thread,
whereas the succinic amide ester methylene groups (Hc and
Hd) are each shielded by > 1.3 ppm in the rotaxane. A similar
Figure 3. 1H NMR spectra (400 MHz) of: a) Thread E-5 and b) rotax-
ane E-1 in CDCl3 at 298 K. The assignments correspond to the lettering
1
series of shifts occurs in the H NMR spectra of the other
molecular shuttle pairs. Thus, even at 298 K, the occupancy of
the fumaramide station in E-1, E-2, and E-3 is greater than
95% (the limit we can determine with reasonable confidence
using this method). The occupancy of the alternative, non-
photoactive station in the corresponding maleamide rotax-
anes is similarly high for Z-1 and Z-2. In Z-3 the male-
amide:adipamide occupancy ratio is reduced to approxi-
mately 15:85 (see Supporting Information), which corre-
sponds to a DDG of approximately 1.1 kcalmolꢀ1.
shown in Scheme 1.
It is interesting to note that our predictions of the relative
station-binding affinities from rotaxane yield and hydrogen-
bond lengths and angles are not completely accurate.
Although the maleamide station is significantly populated in
Z-3, the same station does not compete at all with the succinic
amide ester site in Z-1 (Figure 4), even though the yields[20]
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and X-ray structure suggest that the adipa-
mide group should be a better binding site
than the succinic amide ester.
Overall, the discrimination of the mac-
rocycle for the different stations is excellent
and, at temperatures which require substan-
tial energy differences to significantly bias
the population distribution, somewhat
remarkable (most notably between the
fumaramide and succinamide stations in
E-2, which offer virtually identical hydro-
gen-bonding surfaces to the macrocycle). To
probe this further, molecular model-
ing[16,17,21–24] was carried out by simulated
Figure 5. Translational isomerism in fumaramide-succinamide shuttle E-2.[25] Positional discrimination
is excellent (greater than 95:5 at 298 K in CDCl3) even though the fumaramide and succinamide sta-
tions present nearlyidentical surfaces to the macrocycle. The reason for this behavior is the self-bind-
ing of the succinamide station when it is unoccupied
isomer with the fumaramide station occupied (Figure 5). The
use of “self-binding” to compensate for the lack of station
occupancy could prove a useful concept for driving submo-
lecular motion in molecular machines that rely only on weak,
noncovalent interactions.
Received: December 11, 2002 [Z50745]
Keywords: hydrogen bonds · macrocycles · molecular devices ·
.
photochemistry· rotaxanes
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