Operating molecular elevators

Article abstract of DOI:10.1021/ja0543954

Inspired by the concept of multivalency in living systems, two mechanically interlocked molecules have been conceived that incorporate not once or twice but thrice the features of a pH-switchable [2]rotaxane with two orthogonal recognition sites for dibenzo[24]crown-8 (DB24C8), and 2,3-dinaphtho[24]crown-8 (DN24C8)-one a dialkylammonium ion (CH₂NH₂ ⁺CH₂) and the other a bipyridinium dication (BIPY ²⁺). Whereas at low pH, the CH₂NH₂ ⁺CH₂ sites bind the DB24C8/DN24C8 macrocycles preferentially, at high pH, deprotonation occurs with loss of hydrogen bonding and the macrocycles will move to the BIPY²⁺ sites, where they can acquire some stabilizing [π-π] stacking interactions. Such mechanically interlocked molecules have been assembled from a trifurcated rig-like component wherein the dumbbell-like components of three [2]rotaxanes have one of their ends fused onto alternate positions (1,3,5) around a benzenoid core. The rig is mechanically interlocked by a platform based on a tritopic receptor, wherein either three benzo[24]crown-8 or three 2,3-naphtho[24]crown-8 macrocycles are fused onto a hexaoxatriphenylene core. The synthesis of these molecular elevators involves 1:1 complexation, followed by stoppering, i.e., feet are added to the rig. ¹H NMR spectroscopy and cyclic voltammetry, aided and abetted by absorption spectroscopy, have been employed to unravel the details of the mechanism by which the rig and platform components move on the alternate addition of base and acid. For each molecular elevator, the platform operates by taking three distinct steps associated with each of the three deprotonation/reprotonation processes. Thus, molecular elevators are more reminiscent of a legged animal than they are of passengers on freight elevators.

Full text of DOI:10.1021/ja0543954

Published on Web 01/12/2006
Operating Molecular Elevators
Jovica D. Badjic,† Ce´lia M. Ronconi,† J. Fraser Stoddart,*,† Vincenzo Balzani,‡
Serena Silvi,‡ and Alberto Credi*,‡
Contribution from the California NanoSystems Institute and Department of Chemistry and
Biochemistry, UniVersity of California, Los Angeles, 405 Hilgard AVenue,
Los Angeles, California 90095-1569, and Dipartimento di Chimica “Giacomo Ciamician”,
UniVersita` di Bologna, Via Selmi 2, I-40126 Bologna, Italy
Received July 3, 2005; E-mail: alberto.credi@unibo.it; stoddart@chem.ucla.edu
Abstract: Inspired by the concept of multivalency in living systems, two mechanically interlocked molecules
have been conceived that incorporate not once or twice but thrice the features of a pH-switchable [2]rotaxane
with two orthogonal recognition sites for dibenzo[24]crown-8 (DB24C8), and 2,3-dinaphtho[24]crown-8
(DN24C8)sone a dialkylammonium ion (CH2NH2+CH2) and the other a bipyridinium dication (BIPY2+).
Whereas at low pH, the CH2NH2+CH2 sites bind the DB24C8/DN24C8 macrocycles preferentially, at high
pH, deprotonation occurs with loss of hydrogen bonding and the macrocycles will move to the BIPY2+
sites, where they can acquire some stabilizing [π-π] stacking interactions. Such mechanically interlocked
molecules have been assembled from a trifurcated rig-like component wherein the dumbbell-like components
of three [2]rotaxanes have one of their ends fused onto alternate positions (1,3,5) around a benzenoid
core. The rig is mechanically interlocked by a platform based on a tritopic receptor, wherein either three
benzo[24]crown-8 or three 2,3-naphtho[24]crown-8 macrocycles are fused onto a hexaoxatriphenylene core.
The synthesis of these molecular elevators involves 1:1 complexation, followed by stoppering, i.e., feet
are added to the rig. 1H NMR spectroscopy and cyclic voltammetry, aided and abetted by absorption
spectroscopy, have been employed to unravel the details of the mechanism by which the rig and platform
components move on the alternate addition of base and acid. For each molecular elevator, the platform
operates by taking three distinct steps associated with each of the three deprotonation/reprotonation
processes. Thus, molecular elevators are more reminiscent of a legged animal than they are of passengers
on freight elevators.
Introduction
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Natural molecular machines,1,2 such as ATP synthase, myosin,
kinesin, or dynein, are complex and inspiring assemblies3 whose
structures and working mechanisms have been elucidated in a
few cases.4,5 These intriguing systems have prompted scientists
to design and build artificial molecular machines6 by mimicking
their biological counterparts. In this sense, phenomena that
employed in supramolecular chemistry10 and template-directed
synthesis11 in order to construct functional molecular devices.
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† University of California, Los Angeles.
‡ Universita` di Bologna.
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J. AM. CHEM. SOC. 2006, 128, 1489-1499
1489

A R T I C L E S
Scheme 1 a
Badjic et al.
a Part a) depicts a schematic representation of a switchable [2]rotaxane composed of a rod-shaped component bearing two different recognition sites,
encircling a dumbbell-shaped component. As shown in part b), the recognition sites are a dialkylammonium center (-NH2+-) and a bipyridinium (BIPY2+
)
unit, which serve as stations for the dibenzo[24] crown-8 (DB24C8) component.22b The preferred -NH2+- center for the DB24C8 is related to the formation
of strong hydrogen bonds. On addition of base, the -NH2+- center is deprotonated and the DB24C8 moves to the BIPY2+ unit, where donor-acceptor
interactions become stabilizing. In part c) is shown the equilibrium between the tris-crown ether 2 and the tris-ammonium ion [3H3]3+, which lies to the right
in favor of the superbundle in solvents.25a
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The concept of multivalency9 is exemplified in many living
systems. The recognition of carbohydrate ligands by bacterial
and mammalian lectins is only one example of this phenomenon.
Specific inhibition of recognition events of this type has been
proposed as therapeutic modalities for the neutralization of
bacterial toxins, the prevention of viral and bacterial infections,
and the treatment of cancer. Transferring this concept from
natural settings into an unnatural, wholly synthetic one has
already been investigated during the preparation of some
intricate supramolecular assemblies.20 Stimulated by the poten-
tial of the multivalency in building stable and yet complex
molecular assemblies, we have recently constructed, using the
bottom-up approach, a nanoscale molecular elevator that
incorporates and expresses multivalency in its structure and
operation.21 This molecular elevator derives from a switchable
[2]rotaxane22 which comprises a ring component encircling a
dumbbell-shaped component bearing two different recognition
centers (Scheme 1). One of the recognition centers is a
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A R T I C L E S
Scheme 2 a
a The trifurcated guest salt [4H3][PF6]6 and the tritopic host 2 in a CHCl3/MeCN solution (3.0 mL, 2:1) form a 1:1 adduct (superbundle) that was converted
to the molecular elevator [5H3][PF6]9 in the reaction with (i) 3,5-di-tert-butylbenzyl bromide, followed by (ii) counterion exchange (NH4PF6/MeOH/H2O).
secondary dialkylammonium (-NH2+-) center and the other
is a bipyridinium (BIPY2+) unit. They show different affinities
toward dibenzo[24]crown-8 (DB24C8), the ring component
present in the [2]rotaxane. Previously, we have demonstrated,
using a variety of techniques, that in both Me2CO and MeCN,
the DB24C8 ring resides exclusively around the (-NH2+-)
center. X-ray crystallography has revealed23 that this preference
results from a combination of strong [+NsH‚‚‚O] hydrogen-
bonding and weak [CsH‚‚‚O] interactions, amplified by some
stabilizing [π-π] stacking forces between the components.
Upon addition of an excess of the base iPr2NEt to the
[2]rotaxane in (CD3)2CO solution, deprotonation of the am-
monium recognition site occurs. As a result, the intercomponent
hydrogen bonds are destroyed and the DB24C8 ring moves to
the BIPY2+ recognition site as a consequence of Brownian
motion.24 However, the original co-conformation can be restored
by the addition of the acid CF3CO2H, since the protonation of
the (-NH2+-) recognition site is followed by shuttling of the
ring by means of further Brownian movement back to the re-
formed (-NH2+-) center. The switching of the ring between
the two recognition sites can be monitored by 1H NMR
spectroscopy and by electrochemical techniques.
The synthesis of the [2]rotaxane was achieved by the
formation of a stable 1:1 complex by threading of a precursor
thread containing the (-NH2+-) center with the ring, followed
by stoppering at the threads’ open ends to interlock the ring
mechanically into place. In pursuit of a yet more intricate
threaded structure than the switchable [2]rotaxane (Scheme 1a),
we designed a molecular elevator.21 The enhanced stability
offered by the molecular elevator can be achieved in two
different ways: (1) by clustering together multiple copies of
the recognition centers in order to act in a multivalent fashion25
and (2) by modifying one of the components in order to effect
stronger hydrogen bonding and/or [π-π] stacking interactions.
For our initial investigations on multivalency using the two
nondegenerate recognition centers, we synthesized the first
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A R T I C L E S
Scheme 3 a
Badjic et al.
a The trifurcated guest salt [4H3][PF6]6 and the tritopic host 7 in a CHCl3/MeCN solution (3.0 mL, 2:1) form a 1:1 adduct (superbundle) that was converted
to the molecular elevator [8H3][PF6]9 in the reaction with (i) 3,5-di-tert-butylbenzyl bromide, followed by (ii) counterion exchange (NH4PF6/MeOH/H2O).
generation molecular elevator from two components. A trifur-
cated rig-like component bears three of the dumbbell-like
components of the [2]rotaxane fused at one of their ends to a
central aromatic core. The rig is interlocked by a tritopic receptor
in the form of a tris-crown ether derivative 2. This tris-crown
ether consists of three benzo[24]crown-8 macrorings fused onto
a triphenylene core. Once the molecular elevator has been
formed, the tris-crown ether can be induced to stop at the two
different levels, following the protocol of the addition of acid
and base established for the [2]rotaxane (Scheme 1).
The objective of this work was to study and compare the
preparation, characterization, and operation of two generations
of the trivalent mechanically interlocked molecular machiness
molecular elevatorssin order to understand the properties and
operational mechanisms of these kinds of artificial machines
as a prelude to optimizing their performance. To achieve this
goal we have modified the tritopic receptor in the [5H3][PF6]9
by introducing dioxynaphthalene π-electron-rich units onto the
termini. The extended aromatic units confer stronger electron-
donating power compared with the simple benzo units. These
additional structural features should direct and enhance the
formation of [π-π] stacking and charge-transfer (CT) interac-
tions with the electron-acceptor bipyridinium (BIPY2+) units.26
Herein, we report specifically (1) the synthesis of two tris-crown
ether derivatives containing catechol and 2,3-dioxynaphthalene
π-electron-rich units, respectively, to give the first and second
generations of the molecular machines that act like nanometer-
scale elevators; (2) the elevators’ characterization by mass
spectrometry and 1H NMR spectroscopy; (3) the chemical
1
switching processes by H NMR spectroscopy; and (4) fluo-
rescence titration (Job plots), UV-vis spectroscopy, and
electrochemical switching of these molecular elevators in
solution.
Results and Discussion
Synthesis. The molecular elevators [5H3][PF6]9 and [8H3]-
[PF6]9 were synthesized27 using a template-directed approach
(Schemes 2 and 3) in 33 and 23% yield, respectively. The
superbundles were first assembled as 1:1 adducts between the
trifurcated rig-like component [4H3][PF6]6 and the tris-crown
ethers 2 and 7, respectively, in CHCl3/MeCN (3:2). These 1:1
adducts in CHCl3/MeCN (3:2) were next reacted with 3,5-di-
tert-butylbenzyl bromide followed by counterion exchange
(NH4PF6/MeOH/H2O) to afford the molecular elevators [5H3]-
(26) (a) Ballardini, R.; Balzani, V.; Credi, A.; Gandolfi, M. T.; Langford, S. J.;
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(27) Full experimental procedures for all synthetic steps are available in the
Supporting Information.
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A R T I C L E S
[PF6]9 and [8H3][PF6]9 which, along with the rig component
[6H3][PF6]9, were characterized by mass spectrometry, 1H and
13C NMR spectroscopies, and also absorption and fluorescence
spectroscopies and electrochemistry.
demonstrate that the platforms’ tris-crown ethers bind selectively
with the three -NH2+- centers in the legs of the trifurcated
rigs. The resonances of the trifurcated rigs’ aromatic core
protonssnamely, Hg in [6H3][PF6]9 (∆δ ) -0.54 and -0.59
for the molecular elevators [5H3][PF6]9 and [8H3][PF6]9, re-
spectively) and Hf in 2 and 7 (∆δ ) -0.33 and -0.40 for
molecular elevators 5H3][PF6]9 and [8H3][PF6]9, respectively)s
are shifted upfield significantly relative to the chemical shifts
of the analogous protons in the separate components, indicating
that there are some [π-π] stacking interactions of the central
aromatic cores of the components with each other.
Inspection of the region between δ 3.8 and 4.6 ppm in the
1H NMR spectra (Figure 2a,b) reveals that the protons Hd/d′ and
He/e′ in the tris-crown ether derivatives 2 and 7 separate into
two different sets of signals as a consequence of losing their
planes of symmetry orthogonal to the principal axes in the
molecules. In other words, the pairs of protons in each of the
O-methylene groups that are directed toward the hub of [6H3]-
[PF6]9 become diastereotopic with respect to those which are
directed away from the hub. Thus, all the 1H NMR spectroscopic
evidence supports the mechanically interlocked, triply threaded
structures proposed in Schemes 2 and 3 for the molecular
elevators [5H3][PF6]9 and [8H3][PF6]9.
Characterization. High-resolution electrospray ionization
(HR-ESI) mass spectrometry revealed (Figure 1) that the most
intense peaks in the spectra occurred at m/z ) 1331.1704 and
1381.1919 for the [5H3][PF6]9 and [8H3][PF6]9, respectively,
with an isotope distribution corresponding to the [M - 3PF6]3+
ion. This result supports the structural assignments of the
mechanically interlocked bundles shown in Schemes 2 and 3.
The compounds 2, 7, [6H3][PF6]9, [5H3][PF6]9, and [8H3]-
[PF6]9 were all characterized by 1H NMR spectroscopy (Figure
1
2), including H-1H COSY and TROESY two-dimensional
experiments in order to achieve full assignments in the cases
of [5H3][PF6]9 and [8H3][PF6]9. The 1H NMR spectra of [5H3]-
[PF6]9 and [8H3][PF6]9 reveal (Figure 2a,b) a complex array of
resonances corresponding to triply threaded, mechanically
interlocked molecules with averaged C3V symmetry. Three more
1
features are highlighted by the H NMR spectroscopic results,
namely (i) the interlocked nature of the two components in both
molecular elevators, (ii) the stabilization in both molecular
elevators by [π-π] stacking interactions between the aromatic
cores of the individual components, and (iii) the diastereotop-
icities of the OCH2 protons in crown ethers 2 and 7 as soon as
they form 1:1 adducts. These points are now discussed in turn.
The characteristic downfield shifts and multiplicities25 of the
resonances for the methylene protons adjacent to the secondary
dialkylammonium (-NH2+-) centerssspecifically, Hj and Hk
resonating at δ 4.92 and 4.79 ppm in the case of [5H3][PF6]9,
and at δ 4.92 and 4.83 ppm in the case of [8H3][PF6]9s
Incorporation of naphtho groups into the tris-crown ether
derivative 7 provides the possibility of [π-π] stacking interac-
tions between the bipyridinium units of the rigs and the
1
dioxynaphthalene units in the tris-crown ether. The H NMR
spectra (Figure 2) of the two molecular elevators indicate
evidence for [π-π] stacking interactions in solution: the signals
for the Ho protons in bipyridinium units are successively shifted
upfield, that is, from δ 9.0 to 8.82 to 8.70 ppm for [6H3][PF6]9
Figure 1. High-resolution electrospray ionization (HR-ESI) mass spectrometry: (a,c) experimental isotopic distribution with peaks at m/z ) 1331.1704 and
1381.1919 corresponding to the [M - 3PF6]3+ ions for the molecular elevators [5H3][PF6]9 and [8H3][PF6]9, respectively; (b,d) calculated isotopic distri-
bution with peaks at m/z ) 1331.1756 and 1381.5256 corresponding to the [M - 3PF6]3+ ions of the molecular elevators [5H3][PF6]9 and [8H3][PF6]9,
respectively.
9
J. AM. CHEM. SOC. VOL. 128, NO. 5, 2006 1493

A R T I C L E S
Badjic et al.
Figure 2. 1H NMR spectra (500 MHz, 298 K) recorded on (a) [5H3][PF6]9 (in CD3CN), (b) [8H3][PF6]9 (in CD3CN), (c) [6H3][PF6]9 (in CD3CN), (d) the
tris-crown ether 2 (in CDCl3), and (e) the tris-crown ether 7 (in CDCl3).
and the molecular elevators [5H3][PF6]9 and [8H3][PF6]9,
respectively.
units. Fluorescence excitation spectra show that an efficient
energy transfer from the peripheral chromophoric groups to the
central hexaoxytriphenylene unit takes place, as can be expected
on the basis of their excited-state energies. The luminescence
bands of 2 or 7 can still be observed in the corresponding
molecular elevators, but their intensities are reduced by factors
of more than 200 in the case of [5H3]9+ and of about 70 in the
case of [8H3]9+. The fluorescence band, originating from [π-π]
stacking of the hexaoxytriphenylene and triphenylbenzene units,
that was observed25 for related superbundle systems cannot be
seen for the molecular elevators. Such quenching phenomena
are most likely related to electron-transfer processes involving
the bipyridinium units, which are easily reducible (vide infra).
Electrochemical Properties. The molecular elevators contain
several electroactive units in their molecular components, and
are therefore expected to exhibit a rich redox behavior. In the
potential window examined (from -2 to +2 V vs SCE), the
rig component [6H3]9+ shows two reversible reduction processes
and no oxidation (Table 1). Chronoamperometric experiments
indicate that each reduction process involves the exchange of
three electrons. Since it is well known29 that the 4,4′-bipyri-
dinium unit undergoes two successive, reversible monoelectronic
reduction processes at about -0.4 and -0.8 V versus SCE, we
conclude that the three BIPY2+ units of [6H3]9+ are equivalent
and behave independently of one another. The tris-crown ethers
2 and 7 show three irreversible oxidation processes and no
reduction (Table 1).
Absorption and Fluorescence Spectra. The electronic
absorption spectra of the molecular elevators [5H3]9+ and
[8H3]9+ in MeCN solution (see Supporting Information) show
bands in the near-UV region that can be assigned to transitions
localized on the various chromophoric units28 contained in the
molecular components, namely 1,3,5-triphenylbenzene, hexaoxy-
triphenylene, and 1,2-dioxybenzene or 2,3-dioxynaphthalene in
the case of [5H3]9+ or [8H3]9+, respectively. The absorption
spectra of the molecular elevators, however, differ from the sum
of the spectra of their separated rig and tris-crown ether
components, indicating the presence of intercomponent elec-
tronic interactions. However, no new absorption band at
wavelengths longer than 400 nm, typical of donor-acceptor
interactions between the electron-rich units of the tris-crown
ether components and the electron-deficient bipyridinium units
of the rig, can be seen.
The intense fluorescence band of the 1,3,5-triphenylbenzene
unit (λmax ) 359 nm for model compound [3H3]3+ 25
) is strongly
quenched in the rig compound [6H3]9+, most likely because of
an electron-transfer process from the excited state of the
triphenylbenzene core to a BIPY2+ unit in one of the three legs.
Both tris-crown ethers 2 and 7 exhibit the typical28 fluorescence
of their hexaoxytriphenylene core (λmax ) 383 nm) and no
emission from their 1,2-dioxybenzene or 2,3-dioxynaphthalene
(28) (a) Berlman, I. B. Handbook of Fluorescence Spectra of Aromatic
Molecules; Academic Press: New York, 1965. (b) Montalti, M.; Credi,
A.; Prodi, L.; Gandolfi, M. T. Handbook of Photochemistry, 3rd ed.; CRC
Press: Boca Raton, FL, in press.
(29) Monk, P. M. S. The Viologens. Physicochemical Properties, Synthesis
and Application of the Salts of 4,4′-Bipyridine; Wiley: Chichester, U.K.,
1995.
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1494 J. AM. CHEM. SOC. VOL. 128, NO. 5, 2006

Operating Molecular Elevators
A R T I C L E S
Table 1. Electrochemical Data for the Molecular Elevators, Their
subjected to basic conditions. Addition of a slight excess of
weakly nucleophilic bases, e.g., 1,8-diazabicyclo[5.4.0]undec-
7-ene (DBU), 1,4-diazabicyclo[2,2,2]octane (DABCO), hex-
amethyldisilazane (HMDSZ), quinuclinide, 2,6-lutidine, and
potassium tert-butoxide (t-BuOK), to [5H3][PF6]9 in different
solvents (Table 2) led to either incomplete deprotonation of the
-NH2+- centers or decomposition of the [5H3][PF6]9. Incom-
Molecular Components, and Model Compoundsa
reduction
b
c
compound
E1
′
2
E1/2′′ b
oxidation Ep
/
HMTPd
2e
+1.02
+0.99
+0.94
7e
DBV2+ e,f
[6H3]9+
66+ g
-0.342
-0.347
-0.350
-0.340
-0.528
-0.343
-0.542
-0.779
-0.793
-0.795
-0.764
-0.879
-0.764
-0.897
1
plete deprotonations were reflected in complicated H NMR
spectra, whereas decomposition was signaled by the develop-
[5H3]9+
56+ g
+1.08h
+1.09h,i
+1.09h
+1.10h,i
1
ment of a dark blue color and ill-defined H NMR spectra. In
the case of incomplete deprotonation, subsequent addition of
an equivalent amount of trifluoroacetic acid (TFA) regenerated
[8H3]9
86+ g
1
the H NMR spectrum of [5H3][PF6]9, fully suggesting the
a MeCN solution, 5.0 × 10-4 mol L-1, 0.05 mol L-1 tetraethylammonium
hexafluorophosphate, glassy carbon, 298 K. b Half-wave potential values
of reversible processes in volts versus SCE; experimental error, (5 mV.
c Irreversible processes, potential values in volts versus SCE obtained from
DPV peaks; experimental error, (10 mV. d 2,3,6,7,10,11-Hexamethoxy-
triphenylene. e The redox behavior is not affected by the addition of
P1-t-Bu base and trifluoroacetic acid. f 1,1′-Dibenzyl-4,4′-bipyridinium.
g Obtained by deprotonation of the corresponding protonated form with
3.3 equiv of P1-t-Bu base. h First oxidation process; see text for details.
i Process characterized by a much lower current intensity compared to the
corresponding protonated species.
reversibility of the protonation/deprotonation process and
indicating that these particular bases were simply not strong
enough to cause deprotonation at all three -NH2+- centers.
These results are in agreement with our previous observation25b
that a mechanically interlocked molecular bundle can be fully
deprotonated when it is subjected to very strong base (t-BuOK).
By contrast, the triply threaded supramolecular bundle can be
easily deprotonated25a using a range of weak bases. The tris-
crown ether hosts affect significantly the pKa values of the
trisammonium guest within the mechanically interlocked mo-
Comparison with model compounds allows for a safe
assignment of each process to a specific redox-active unit. In
both cases, the first oxidation process is attributed to the
hexaoxytriphenylene core, and the two successive oxidation
processes are attributed to the dioxybenzene (in the case of 2)
or dioxynaphthalene (in the case of 7) units interacting with
one another. The molecular elevators [5H3]9+ and [8H3]9+ show
both reduction and oxidation processes. On reduction, they
exhibit two successive reversible three-electron processes (Table
1 and Figure 3), at potential values very similar to those found
for the rig component [6H3]9+. This observation indicates that
in the molecular elevators the three BIPY2+ units are again
equivalent, behave independently from one another, and are not
engaged30 in electron donor-acceptor interactions with the
dioxyaromatic units of the tris-crown ether platform. Such a
result is fully consistent with the location of the platform
component on the upper level, with its three crown ether rings
encircling the -NH2+- centers, in agreement with the 1H NMR
spectroscopic data. On the oxidation side, the molecular
elevators show one irreversible process (Table 1), assigned to
oxidation of the hexaoxybenzene core, and other broad volta-
mmetric peaks at potential values higher than +1.3 V, assigned
to irreversible oxidation of the peripheral dioxyaromatic units.
Because of their irreversible nature and poor definition, these
processes will not be further discussed.
Chemical Switching. One of the reasons for assembling
mechanically interlocked compounds, such as the molecular
elevators [5H3][PF6]9 and [8H3][PF6]9, is to construct machines
on the nanoscale level, wherein their operation can be controlled
through acid/base external input. We have already established
that the tris-crown ether components 2 and 7 reside exclusively
on the -NH2+- recognition centers (upper level). Bases that
can deprotonate these centers could act as chemical inputs,
promoting the movement of the tris-crown ethers toward the
bipyridinium (BIPY2+) units (lower level).
The choice of the base for deprotonation of -NH2+- centers
in [5H3][PF6]9 was complicated on the account of our experi-
mental observations, in line with our previous report22a that
BIPY2+ units can undergo a structural change if they are
Figure 3. (a) Cyclic voltammetric curves for the reduction of the BIPY2+
units in [8H3]9+ (blue line), and in the deprotonated species [8H2]8+ (dotted
line), [8H]7+ (dashed line), and 86+ (red line), obtained from [8H3]9+ on
successive additions of P1-t-Bu base. Conditions: MeCN solution, 5.0 ×
10-4 mol L-1 molecular elevator, 0.05 mol L-1 tetraethylammonium
hexafluorophosphate, glassy carbon electrode, 0.2 V s-1, 298 K. (b) Diagram
of the potential values for the reduction processes of the BIPY2+ units of
[8H3]9+ (b) and [6H3]9+ (O) (top), on addition of base to afford 86+ and,
respectively, 66+ (middle), and after reprotonation with an acid, a stoichio-
metric amount with respect to the added base (bottom).
9
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A R T I C L E S
Badjic et al.
Table 2. Switching Process Using Different Bases
pKa
temperature/
K
base
MeCN
solvent
deprotonation
1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU)
1,4-diazabicyclo[2,2,2]-octane (DABCO)
potassium hexamethyldisilazane (KHMDSZ)
quinuclinide
18.3
18.3
26.0a
9.80a
14.0
19.0a
11.4a
18.0
18.2
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
CD3CN
(CD3)2CO, CD3CN, (CD3)2SO
CD3CN
(CD3)2CO
298
298
298
298
298
298
235-298
298
decomposition of BIPY2+ units
incomplete, reversiblea,b
decomposition of BIPY2+ units
incomplete, reversibleb
2,6-lutidine
incomplete, reversibleb
potassium tert-butoxide (t-BuOK)
N-ethyldiisopropylamine (EDIPA)
tributylamine (TBA)
decomposition of BIPY2+ units
incomplete, reversibleb
incomplete, reversibleb
N,N,N′,N′-tetramethyl-1,8-naphthalene-
298
incomplete, reversibleb
diamine (proton-sponge)
N-tert-butyl-N′,N′,N′′,N′′,N′′′,N′′′-hexamethyl-
phosphorimidic triamide (P1-t-Bu)
26.5
CD3CN
298
complete, reversibleb
a In DMSO. b Upon addition of TFA.
Figure 4. 1H NMR spectra (600 MHz, in CD3CN, 4.3 mM, and 298 K) recorded on [5H3][PF6]9 before (a) and after addition of (b) 1.7 and (c) 3.4 equiv
of the phosphazene (N-tert-butyl-N′,N′,N′′,N′′,N′′′,N′′′-hexamethylphosphorimidic triamide) base. The original spectrum is regenerated (d) on addition of 3.4
equiv of trifluoroacetic acid.
lecular elevator [5H3][PF6]9 or bundle,25 a phenomenon that will
be a subject for discussion in a future paper.
δ 7.42 to 7.70 ppm in the case of Hg, and from δ 7.35 to 7.70
ppm in the case of Hf. These results demonstrate the absence
of any [π-π] stacking interactions upon addition of base.
Moreover, the O-methylene protons (Hd/d′ and He/e′) retain their
diastereotopicities, indicating that the two components are still
interacting intimately with each other.
On addition of 1.7 equiv of the strong phosphazene base (P1-
t-Bu) to a solution of [5H3][PF6]9 in CD3CN, extensive
broadening of peaks occurred, indicating the presence of more
than one species, undergoing slow exchange31 on the 1H NMR
time scale (Figure 4b). Upon addition of a slight excess (3.4
equiv) of the phosphazene base, significant changes were
observed (Figure 4c) in the spectrum. The resonances for the
methylene protons Hj and Hk in [5H3][PF6]9 were shifted upfield
from δ 4.92 and 4.79 ppm to δ 3.62 and 3.53 ppm, respectively,
indicating complete deprotonation of all three -NH2+- centers.
The chemical shifts of all the other protons in both the 2 and
[6H3][PF6]9 components of the molecular elevator [5H3][PF6]9
changed (Figure 4c) dramatically as well. In particular, the
resonances for the central aromatic core protons, Hg in the [6H3]-
[PF6]9 component and Hf in the hexaoxytriphenylene core of
the tris-crown ether component 2, were shifted downfield from
1H NMR spectroscopic studies revealed that the affinity of
tris-crown ether component 2 for the -NH2+- centers decreases
noticeably upon addition of 3.4 equiv of the phosphazene bases
which deprotonates the NH2+ centerss and the tris-crown ether
2 moves (Figure 4c) to the BIPY2+ recognition sites. This move-
ment is indicated by the remarkable chemical shifts associated
with the BIPY2+ and p-xylyl methylene protons, demonstrating
that the tris-crown ether 2 is now associated with the BIPY2+
recognition sites. In addition, the Ho protons in the BIPY2+ units
are shifted downfield from δ 9.0 to 9.3 ppm, a trend which is
indicative of the formation of [CsH‚‚‚O] interactions with the
1
oxygen atoms in the tris-crown ether. The original H NMR
(30) It is well known that when BIPY2+ units are surrounded by electron donors
such as the dioxybenzene units of DB24C8, their reduction potentials
become displaced to more negative values by more than 150 mV because
of donor-acceptor interactions. See ref 22b.
(31) Elizarov, A. M.; Chiu, S. H.; Stoddart, J. F. J. Org. Chem. 2002, 67, 9175-
9181.
spectrum was regenerated in every detail upon addition of a
slight excess of TFA to the NMR sample previously treated
with base, indicating that the switching process is pH-controlled
and completely (quantitatively) reversible.
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1496 J. AM. CHEM. SOC. VOL. 128, NO. 5, 2006

Operating Molecular Elevators
A R T I C L E S
Figure 5. 1H NMR spectra (600 MHz, in CD3CN, 4.0 mM, and 298 K) recorded on [8H3][PF6]9 before (a) and after (b) addition of 3.4 equiv of the
phosphazene (N-tert-butyl-N′,N′,N′′,N′′,N′′′,N′′′-hexamethylphosphorimidic triamide) base. The original spectrum is regenerated (c) on addition of 3.4 equiv
of trifluoroacetic acid.
For the molecular elevator [8H3][PF6]9, the operation (Figure
5) is somehow similar to that of [5H3][PF6]9. Upon addition of
3.4 equiv of the phosphazene base to [8H3][PF6]9 in CD3CN
solution, complete deprotonation of -NH2+- centers occurred
(Figure 5b) and the tris-crown ether 7 migrated to the BIPY2+
recognition sites. The structure of this new hexacationic
compound 86+, in which the elevator is at the lower level, is
confirmed by the chemical shifts observed (Figure 5b) in the
1H NMR spectrum. Upfield shifts of the methylene protons Hj
and Hk in [8H3][PF6]9 from δ 4.92 and 4.83 ppm to δ 3.23 and
3.64 ppm, respectively, imply complete deprotonation of the
three -NH2+- centers. The resonances for the central aromatic
core protons (Hg, Hh, and Hi) are shifted from δ 7.40, 7.60, and
7.60 ppm, respectively, to δ 7.60, 7.50, and 7.29 ppm,
respectively, revealing, once more, the absence of any [π-π]
stacking interactions upon addition of base. The O-methylene
protons in the tris-crown ether 7 retain their diastereotopicities,
indicating that the two components are interacting with each
other. In addition, upfield shifts in the trifurcated protons Hs,
Ht, and Hu in the vicinity of the three 3,5-di-tert-butylbenzyl
stoppers and the p-xylyl protons, Hl and Hm, suggest that the
tris-crown ether 7 interacts asymmetrically with the BIPY2+
recognition sites. It is important to note that the downfield shift
of the Ho protons in the BIPY2+ units is much more pronounced
for [8H3][PF6]9 (from δ 8.70 to δ 9.60 ppm) than for [5H3]-
[PF6]9 (from δ 9.00 to 9.30 ppm). This observation can be
explained by the better [π-π] stacking interactions involving
naphtho rather than benzo aromatic units with the BIPY2+
recognition sites. Such [π-π] stacking enforces the [CsH‚‚‚O]
interactions and, therefore, affects the chemical shift of the Ho
protons. On addition of TFA, the original spectrum (Figure 5c)
is regenerated, demonstrating, once again, that the switching
process is reversible.
observed in cyclic voltammetric experiments, but they are
displaced to more negative values (Table 1 and Figure 3). Such
changes cannot be a result simply of deprotonation of the
-NH2+- centers, because the potential values for reduction of
the BIPY2+ units in the rig component [6H3]9+ are identical to
those in the corresponding deprotonated species, 66+. Hence,
the results obtained show30 that, in the deprotonated molecular
elevators 56+ and 86+, the BIPY2+ units in the three legs,
although remaining equivalent and independent of one another,
are surrounded by the electron donor DB24C8-type rings of
the platform. The changes in reduction potential can be fully
reversed by addition of a stoichiometric amount of TFA with
respect to the previously added base. It is worthwhile to note
that the negative shift of the potential for the reductions of the
BIPY2+ units with respect to the rig component is larger for
86+ than it is for 56+. Such a larger shift, which indicates that
the BIPY2+ units experience stronger electron donor-acceptor
interactions in the former elevator than in the latter, is in
agreement with the 1H NMR spectroscopic data and is expected
on the basis of the better π-electron donor ability of the
dioxynaphthalene compared to the dioxybenzene units. This
observation is an important one since the control of the
intercomponent interactions allows the modulation of the
energies associated with the elevators’ molecular motions.
It is also important to consider the second reduction process
of the BIPY2+ units. For the molecular elevators such a process
is negatively shifted compared to the same process in the rig
component, while it was not shifted in the [2]rotaxane [1H]3+
(Scheme 1) studied previously.22b The lack of shift in the case
of the [2]rotaxane was attributed to the shuttling of the DB24C8
ring away from the monoreduced bipyridinium unit, in keeping
with the fact that one-electron reduction of the BIPY2+ unit
disrupts the charge-transfer interactions with electron donors.
In the present case, we have to conclude that the displacement
of the platform away from the monoreduced bipyridinium units
does not take placesat least on the time scale of the electro-
The elevators’ switching triggered by base and acid stimula-
tion can also be clearly monitored by voltammetric experiments
performed in MeCN solution, using the reduction processes of
the bipyridinium units as a probe.32 On deprotonation of [5H3]9+
and [8H3]9+ with 3.3 equiv of the phosphazene base P1-t-Bu,
two reversible three-electron reduction processes are still
(32) The oxidation processes of the molecular elevators, being irreversible
and poorly defined, are not useful for monitoring the switching of the
systems.
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A R T I C L E S
Badjic et al.
voltammetric and spectroscopic properties of the compounds
upon titration with the phosphazene base. On addition of the
base, two new voltammetric waves are revealed at more negative
potentials compared to the initial reduction waves (Figure 3a).
On the basis of the above results, these new peaks have to be
assigned to the reduction of BIPY2+ units encircled by the crown
ether rings of the platform component. The current intensity of
the peaks, corresponding to the reduction of the complexed
BIPY2+ units, increases linearly on addition of 1, 2, and 3 equiv
of base, at the expense of the intensity of the peaks correspond-
ing to the reduction of the free BIPY2+ units (Figure 3a).
However, the distribution of the free and complexed BIPY2+
units among the elevator molecules cannot be determined solely
from these observations; in other words, it cannot be assessed
whether the addition of 1 equiv of base forms exclusively the
species with only one crown ether ring displaced, or a statistical
distribution of species with none, one, two, or three rings
displaced. We have therefore monitored the changes in the
absorption spectra upon titration with base for both molecular
elevators. Although the changes appear (Figure 6) to be
complicated, a closer look reveals that the absorption curves
can be grouped into three families exhibiting monotonic
variations.
Figure 6. Absorption spectral changes observed upon titration at 298 K
of a 4.0 × 10-6 mol L-1 MeCN solution of the molecular elevator [8H3]9+
with the P1-t-Bu base. Insets (a) and (b) show a magnification of the 272-
282 nm region and the titration curve obtained from the absorbance changes
at 277 nm, respectively.
chemical experimentsspresumably because it is strongly acti-
vated owing to the structural complexity of the molecular
elevators.
A plot of the absorbance values at a selected wavelength,
e.g., at 277 nm (Figure 6), on titration of the molecular elevator
with base shows the presence of three quite distinct steps,
indicating that the three deprotonation processes are not
equivalent. Molecular modeling (see Supporting Information)
shows that the species in which two (or one) ring(s) surround
(a) -NH2+- center(s) and one (or two) rings surround(s) (a)
BIPY2+ unit(s) are sterically possible. Hence, for each molecular
elevator, the platform operates by taking three distinct steps
associated with each of the three deprotonation processes. In
this regard, the molecular elevator is more reminiscent of a
legged animal than it is of the passenger elevator.
The chemically driven operation of [5H3]9+ and [8H3]9+ also
leads to reversible changes in the absorption and fluorescence
spectra (see Supporting Information). In particular, the elevators’
motions can be monitored by observing the changes in absor-
bance at selected wavelengths, e.g., 310 nm, on successive
additions of base and acid. The signal change, after some initial
loss in the early cycles, reaches stability, indicating that the
process can be repeated several times. This behavior is mirrored
by the weak fluorescence band with λmax around 380 nm,
observed for both molecular elevators, that increases and,
respectively, decreases in intensity on successive additions of
stoichiometric amounts of base and acid.
It is interesting at this point to reflect upon the energies
associated with the mechanical switching of these molecular
machines (Scheme 4). The driving force for the motion of the
platform from the upper to lower levels (base stroke) is provided
More detailed information on the mechanism of the elevators’
motions can be obtained by observing the changes in the
Scheme 4. Base-Acid-Controlled Mechanical Switching in the Molecular Elevatorsa
a The graph reports a simplified representation of the potential energy of the system as a function of the position of the platform relative to the rig for each
co-conformation.
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Operating Molecular Elevators
A R T I C L E S
Conclusions
by the electron donor-acceptor interactions between the
electron-donor units of the platform and the BIPY2+ electron-
acceptor units of the rig. The driving force for the motion of
the platform from the lower to upper levels (acid stroke) is
given by the larger stabilization energy offered to the platform’s
rings by the -NH2+- centers compared to the BIPY2+ units.
The energies available for the relevant movements can be
estimated21 from the redox potential and thermodynamic
constant values. The energy released in the base stroke amounts
The research described in this paper reveals how the concept
of multivalency can be harnessed in the construction of
mechanically interlocked molecular components beyond the
realm of a relatively simple bistable [2]rotaxane. The two
molecular elevators that have been investigated in detail in
solution can be likened to a combination of three bistable
[2]rotaxanes incorporated within one molecule in each case.
Interestingly, when it comes to investigating how the rig and
platform components move with respect to each other in these
molecules under chemical stimuli, the recognition sites operate
not in unison but rather one after the other. Coupled with the
message that the force potentially generated during such
movements is not insignificant, when compared with that
generated by biological motors, we have gathered enough
information and encouragement to look forward to the next
challengesthat of pinning down molecular elevators on surfaces
or marshalling them at interfaces.
to ca. 21 and ca. 22 kcal mol-1 for [5H3]9+ and [8H3]9+
,
respectively, and that released in the acid stroke is estimated to
be larger than 4 kcal mol-1 for both molecular elevators. The
better electron-donating ability of the dioxynaphthalene units
compared to the dioxybenzene units is responsible for the larger
driving force associated with the base stroke for [8H3]9+ but it
is, of course, expected to lower the driving force for the acid
stroke.
These large stabilization energies not only provide strong
driving forces for the molecular motion, but also confer a high
positional (co-conformational) integrity upon the elevators,
giving rise to a clear-cut on/off behavior. Since molecular
models show that the distance traveled by the platform is about
0.7 nm, we speculate that the elevators could potentially generate
a maximum force of around 200 pN in the base stroke. Such
force is more than 1 order of magnitude larger than the forces
developed4b by natural linear motors like myosin33 and kinesin.34
In any instance, single-molecule experiments in which a load
is applied to the molecular elevators, e.g., force spectroscopy
experiments,35 will have to be performed in order to investigate
the operation mechanism of such artificial nanomotors and
determine the amount of mechanical work that can be actually
produced.
Acknowledgment. This research was supported by the
National Science Foundation (CHE-9910199, CHE-9974928,
and CHE-0116853) in the United States, the Fundac¸a˜o Coorde-
nac¸a˜o de Aperfeic¸oamento de Pessoal de N´ıvel Superior
(CAPES-C.M.R.-BEX0196/03-7) in Brazil, and the University
of Bologna (Funds for selected topics), Ministero dell’Istruzione,
dell’Universita` e della Ricerca (Supramolecular devices project),
Fondo per gli Investimenti della Ricerca di Base (RBNE19H9K),
and the European Union (Molecular-Level Devices and Ma-
chines Network HPRN-CT-2000-00029 and BIOMACH Project
NMP2-CT-2003-505487) in Italy.
Supporting Information Available: Experimental procedures
and further details; complete list of authors for refs 15c, 16f,
22b, and 26b. This material is available free of charge via the
Internet at http://pubs.acs.org.
(33) Molloy, J. E.; Veigel, C. Science 2003, 300, 2045-2046.
(34) Goldstein, L. S. B. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 6999-7003.
(35) Hugel, T.; Holland, N. B.; Cattani, A.; Moroder, L.; Seitz, M.; Gaub, H.
E. Science 2002, 296, 1103-1106.
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