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A Molecular Elevator

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Science  19 Mar 2004:
Vol. 303, Issue 5665, pp. 1845-1849
DOI: 10.1126/science.1094791

Abstract

We report the incrementally staged design, synthesis, characterization, and operation of a molecular machine that behaves like a nanoscale elevator. The operation of this device, which is made of a platformlike component interlocked with a trifurcated riglike component and is only 3.5 nanometers by 2.5 nanometers in size, relies on the integration of several structural and functional molecular subunits. This molecular elevator is considerably more complex and better organized than previously reported artificial molecular machines. It exhibits a clear-cut on-off reversible behavior, and it could develop forces up to around 200 piconewtons.

Biomotor molecules are extremely complex machines, the detailed structures and precise working mechanisms of which have been elucidated only in a very few cases (1, 2). Chemists are trying to construct much simpler molecular machines as a logical step toward mimicking the actions of biomotor molecules (35). In the past few years, several different kinds (614) of artificial molecular machines have been designed and constructed.

Here, we describe the incrementally staged design, bottom-up construction, characterization, and chemically driven operation of a two-component molecular machine that behaves like a nanometer-scale elevator. This nanoactuator, which is circa (ca.) 2.5 nm in height with diameter of ca. 3.5 nm, consists of a trifurcated riglike component containing two different notches at different levels in each of its three legs that are interlocked by a platform. The platform is made up of loops in the form of three macrocycles, fused trigonally to a central floor, that can be made to stop at the two different levels. The three legs of the rig carry bulky feet that prevent the loss of the platform. The energy needed to raise and lower the platform between the two levels on the rig's legs is supplied by an acid-base reaction. The distance traveled by the platform is about 0.7 nm, and we estimate that the elevator movement from the upper to lower level could generate a force of up to 200 pN.

The molecular elevator has its origin in the molecular shuttle, a degenerate two-station [2]rotaxane (15). The promise of this mechanically interlocked molecule (16) to act as the prototype for the construction of linear motors, based on highly controllable [2]rotaxanes, has been realized recently by redox (8, 11, 12), acid-base (8), and photochemical (11, 13) stimulations. In such systems, a ring component encircles preferentially one of two recognition sites present along the rodlike section of a dumbbell-shaped component. It is possible then (Fig. 1A), by using an appropriate external stimulus, to induce the ring to move in an almost linear fashion from one station to the other. Redox-controllable bistable [2]rotaxanes have already been incorporated as electronically reconfigurable switches into both simple memory and logic circuits (17).

Fig. 1.

(A) Schematic representation of a controllable, bistable [2]rotaxane, containing in its dumbbell-shaped component two different recognition sites or “stations,” to one of which the ring component is attracted much more than the other. The two different states of the molecule can be switched by an external stimulus, such as a change in pH. (B) In the [2]rotaxane [1H]3+, the dumbbell-shaped component contains a –NH2+– center and a BIPY2+ unit as stations for the DB24C8 component (8). In acid, the preferred station for the DB24C8 ring to encircle is the –NH2+– center because of the formation of strong hydrogen bonds. On addition of base, however, the –NH2+– center is deprotonated and the DB24C8 moves to the BIPY2+ unit, where the donor-acceptor interactions become stabilizing. (C) The equilibrium between the tris-crown ether 2 and the tris-ammonium ion [3H3]3+, which lies very much to the right in favor of the superbundle in solvents such as acetonitrile and dichloromethane (21). The graphical representation of the superbundle portrays the good surface-to-surface match between the two interpenetrating components. The dots indicate the [N+–H···O] hydrogen bonds between the –NH2+– centers of [3H3]3+ and the fused DB24C8 rings in 2, and the horizontal dashes, the [π-π] stacking interactions between the central aromatic cores. The superbundle can be disassembled by addition of a base and reassembled by addition of an acid.

Previously, we have described (8, 18) the acid-base switching (Fig. 1B) of the [2]rotaxane [1H]3+ composed of a dumbbell-shaped component containing two different stations, namely, a dialkylammonium (–NH2+–) center and a bipyridinium (BIPY2+) unit, encircled by a dibenzo[24]crown-8 (DB24C8) ring component. We demonstrated, with the use of a variety of techniques, that in both acetone and acetonitrile the DB24C8 ring resides almost exclusively around the –NH2+– center in one of the two possible translationally isomeric forms. X-ray crystallography has revealed (19) that this preference results from a combination of strong [N+–H···O] hydrogen bonding and weak [C–H···O] interactions, augmented more often than not with some stabilizing [π-π] stacking forces. On addition of a base (a tertiary amine) to a solution of [1H]3+, deprotonation of the –NH2+– center occurs. The strong intercomponent hydrogen bonding is destroyed, and the DB24C8 ring moves to the BIPY2+ unit, where it is stabilized by [C–H···O] and [π-π] stacking interactions. Subsequent addition of acid restores the –NH2+– center, and the DB24C8 ring moves back to encircle this recognition site. The shuttling process, which can be followed by nuclear magnetic resonance (1H NMR) spectroscopy and electrochemical techniques, is quantitative (8).

In pursuit of a better fundamental understanding of the nature of multivalency (20) in polytopic hosts and guests, we investigated (21) the acid-base–controlled (Fig. 1C) assembly and disassembly of a triply threaded two-component superbundle. This 1:1 adduct consists of a tritopic host 2, in which three DB24C8 rings are fused together within a triphenylene core, and a trifurcated guest trication [3H3]3+ wherein three dibenzylammonium ions are linked to a central benzenoid core. Fluorescence titration experiments (including Job plots), as well as electrochemical and 1H NMR spectroscopic data, have established the remarkable strength of the superbundle encompassing the triply expressed binding motif revealed by x-ray crystallography in the solid state (21). In acetonitrile solution, the dethreading and rethreading of the 1:1 adduct can be controlled by addition of base and acid.

By incorporating the architectural features (Fig. 1B) of the acid-base switchable [2]rotaxane [1H]3+/12+ into those (Fig. 1C) of the trifurcated trication [3H3]3+, we came up with the design of the molecular elevator shown in Fig. 2. It was synthesized with the use of a template-directed protocol (22) from the trifurcated guest salt [4H3][PF6]6 and the tritopic host 2, which form a 1:1 adduct (superbundle) that can be converted into a mechanically interlocked elevator [5H3]9+ by functionalization of the ends of each leg with bulky 3,5-di-tert-butylbenzyl feet (scheme S1). This compound, and its model [6H3]9+, which were both isolated as their 9PF6 salts, were characterized by 1H NMR spectroscopy, electrochemistry, and absorption and fluorescence spectroscopy.

Fig. 2.

The trifurcated guest salt [4H3][PF6]6 and the tritopic host 2 (each 6.6 mM) in a CHCl3/MeCN solution (3.0 mL, 2:1) form a 1:1 adduct (superbundle) that was, at elevated temperature (75°C), converted to the mechanically interlocked elevator [5H3][PF6]9 in the reaction with (i) 3,5-di-tert-butylbenzylbromide(200 mM), followed by (ii) the counterion-exchange (NH4PF6/MeOH/H2O). Following the same protocol, only without 2, the model compound [6H3][PF6]9 was synthesized.

The 1H NMR spectrum (Fig. 3A) of [5H3][PF6]9 in CD3CN exhibits a complex array of resonances corresponding to a triply threaded, mechanically interlocked molecule with averaged C3v symmetry. Characteristic (18) downfield shifts of the methylene proton resonances next to the –NH2+– centers indicate the preferred binding of the platform's three crown ether loops with the three –NH2+– centers in the legs of the rig. No additional proton resonances were obtained in the 1H NMR spectrum when a CD3COCD3 solution of [5H3][PF6]9 was cooled down to –80°C. These observations confirm that [5H3]9+ exists in the co-conformation shown in Fig. 3D. Addition of a strong, nonnucleophilic phosphazene base to a solution of the elevator in CD3CN caused dramatic changes in the 1H NMR spectrum, particularly in the chemical shifts of the BIPY2+ and p-xylyl methylene protons, demonstrating that the three crown ether loops on the platform are now associated with the three BIPY2+ recognition sites. The addition of <3 equivalents of base led to the extensive line broadening, indicating the presence of several slowly exchanging intermediate co-conformations on the 1H NMR time scale, whereas, after addition (Fig. 3B) of a slight excess (3.4 equivalents), only the hexacationic species 56+, in which the elevator has reached the lower level, is present. The original 1H NMR spectrum was regenerated in every detail on addition of a slight excess of trifluoroacetic acid to the NMR sample treated with the base; i.e., the elevator goes back completely to the upper level.

Fig. 3.

1H NMR spectra (600 MHz, CD3CN, 4.3mM, and 298 K) recorded on [5H3][PF6]9 before (A) and after (B) addition of 3.4 equivalents of the phosphazene base, N-t -butyl-N′,N′,N″,N″,N‴,N‴-hexamethylphosphorimidic triamide. The original spectrum is regenerated (C) on addition of 3.4 equivalents of trifluoroacetic acid. The corresponding operation of the molecular elevator is shown on the right-hand side. The platform is situated on the upper level (D) at the outset. Addition of the base causes the platform to move to the lower level (E). Addition of acid restores the platform to the upper level (F).

Clear evidence for the elevator operating with base and acid inputs was also obtained from electrochemical experiments performed in acetonitrile solution. It is well known (23) that BIPY2+ units undergo two successive, reversible monoelectronic reduction processes at about –0.4 and –0.8 V [compared with a saturated calomel electrode (SCE)]. When BIPY2+ units are surrounded by electron donors such as the catechol rings in DB24C8, their reduction potentials become displaced (8) to more negative values by about 150 to 200 mV. We found that [6H3]9+ (Fig. 2) exhibits two successive reversible three-electron reduction processes at –0.35 V and –0.80 V, indicating that the three BIPY2+ units (i) are equivalent, (ii) behave independently of one another, and (iii) are not engaged in electron donor-acceptor interactions. On deprotonation of the control [6H3]9+ by addition of the phosphazene base, the two reduction waves (Fig. 4A) are almost unaffected. The electrochemical behavior of the molecular elevator [5H3]9+ is quite similar to that of the control [6H3]9+, indicating that the three BIPY2+ units are not interacting with the electron-donating catechol rings at the periphery of the platform. Thus, the initial co-conformation adopted by [5H3]9+ corresponds to the one in which the crown ether loops on the platform all surround the –NH2+– centers on the three-legged rig (on the upper level). On addition of slightly more than 3 equivalents of base, however, the two reduction waves are displaced (Fig. 4A) to more negative potentials, indicating that the three BIPY2+ units in the three legs, although remaining equivalent and independent from one another, are now surrounded by the electron-donating crown ether loops of the platform. The changes in reduction potential can be fully reversed by addition of acid, and the cycle can be repeated without any significant loss of reversibility.

Fig. 4.

(A) Potential values, in V versus SCE, for the reduction processes of the BIPY2+ units of [5H3]9+ (⚫) and [6H3]9+ (◯) (top) on addition of a base to afford 56+ and, respectively, 66+ (middle) and after reprotonation with an acid, a stoichiometric amount with respect to the added base (bottom). (B) Changes in absorbance observed at 310 nm (path length is 4.0 cm) for a 7.1 μM solution of [5H3]9+ on successive addition of stoichiometric amounts of base (yellow areas) and acid (green areas). All experiments were carried out in acetonitrile solution at 298 K.

The chemically driven operation of the molecular elevator [5H3]9+ also leads to reversible changes in the emission and absorption spectra. In acetonitrile solution, [5H3]9+ exhibits a relatively weak emission band with a maximum at ca. 380 nm. On successive additions of stochiometric amounts of the base and acid, the intensity of the band increases and, respectively, decreases. This behavior is also witnessed in the absorption spectrum. The change in absorbance at 310 nm on successive additions of base and acid shows (Fig. 4B) that the process can be repeated several times, with some loss of signal in the first cycles.

The current intensities of the cyclic voltammetric peaks of the “free” and “complexed” BIPY2+ units decrease and, respectively, increase linearly on addition of 1, 2, and 3 equivalents of base (Fig. 5A). These data do not, however, shed any light on the precise mechanism of the platform's operation, i.e., whether the addition of 1 equivalent of base forms exclusively the species with only one loop displaced, or a statistical distribution of species with none, one, two, or three loops displaced. We therefore performed titration experiments and monitored changes in absorption spectra. A plot (Fig. 5B) of the absorbance changes (e.g., at 276 nm) on titration of [5H3]9+ with base shows the presence of three quite distinct steps, indicating that the three deprotonation processes are not equivalent. Thus, addition of the first equivalent of base does not lead to a statistical mixture of differently protonated species but rather causes the first deprotonation process to occur, first of all, in all [5H3]9+ ions, and so on. Molecular modeling (Fig. 5C) shows that the species in which two (or one) loop(s) surround (a) –NH2+– center(s) and one (or two) loop(s) surround(s) (a) BIPY2+ unit(s) are sterically possible. And so, for each [5H3]9+, the platform operates in three discrete steps associated with each of the three deprotonation processes that take [5H3]9+ progressively through [5H2]8+ and [5H]7+ ions to, finally, 56+.

Fig. 5.

(A) Cyclic voltammetric curves for the first three-electron reduction of (from top to bottom) [5H3]9+, [5H2]8+, [5H]7+, and 56+. Conditions were a 0.40 mM molecular elevator, acetonitrile solution with 0.04 M tetraethylammonium hexafluorophosphate as supporting electrolyte, 100 mV s–1, glassy carbon electrode, 298 K. (B) Changes in the absorbance at 276 nm on titration of [5H3]9+ with the phosphazene base in 5.0 μM acetonitrile solution at 298 K. (C) Stepwise motion of the platform down to the legs of the rig on successive deprotonation of its three –NH2+– centers. The structures shown were obtained by molecular mechanics calculations.

From thermodynamic considerations, it can be established [Supporting Online Material (SOM) Text] that the energies available for the relevant movements from the upper to lower levels (base stroke) and from the lower to upper levels (acid stroke) amount to ca. 21 and >4 kcal mol–1, respectively. These large stabilization energies not only provide strong driving forces for the molecular motion, they also confer a high positional (co-conformational) integrity on the elevator, giving rise to a clear-cut on-off behavior. Because the distance traveled by the platform is about 0.7 nm, the nanoactuator can potentially generate a force of up to 200 pN in the motion from the upper to the lower level. Such force is more than one order of magnitude larger than those developed (2) by natural linear motors like myosin and kinesin.

The bundle [5H3]9+, besides operating as a molecular elevator, could also serve other useful functions. The movement of the platform from the upper level, in which the loops surround the –NH2+– centers on the legs, to the lower level, where the loops surround the BIPY2+ units, opens up a potentially large cavity (1.5 nm by 0.8 nm) in 56+ that is closed down again when the system returns to the upper level (Fig. 5C). Such a cavity, whose sides contain three amine functions and whose floor and roof are defined by aromatic rings, could play host to some large guest molecules. Additionally, the base-acid control mechanism might be accompanied by the switching “on” and “off” of a potentially attractive hosting capacity. We also note that, when the platform is on the upper level, the three BIPY2+ units are not engaged in any interactions and so the elevator is free to move its legs, whereas, when the platform is at the lower level, these same legs will be rigidified as well as occupied. Thus, when the platform is on the upper level, the BIPY2+ units could form adducts with other electron donor species present in the solution, whereas this possibility is precluded when the platform resides at the lower level. Also, because the BIPY2+ units lose their electron-accepting character upon reduction (6, 7, 23), the adduct-forming capacity of the three BIPY2+ legs could also be controlled electrochemically.

The molecular elevator has a complex structure that is capable of performing well-defined mechanical movements under the actions of external inputs; i.e., it is possible to produce multivalent compounds (24) capable of performing nontrivial mechanical movements and exercising a variety of different functions on external stimulation.

Supporting Online Material

www.sciencemag.org/cgi/content/full/303/5665/1845/DC1

Materials and Methods

SOM Text

Scheme S1

Figs. S1 and S2

References

References and Notes

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