Rotaxanes: From Template Synthesis to Molecular Devices
Rotaxanes
are mechanically bound molecules, in which an axle is threaded into a wheel and then trapped with
two bulky stopper groups to prevent deslipping. Rotaxanes are usually prepared employing
template effects among which coordination of the two subunits
to a transition metal ion center (e.g. the work of Sauvage), hydrogen bonding between axle and wheel (e.g.
Stoddart,
Vögtle,
Leigh groups), and pi-donor-pi-acceptor
complexes (e.g.
Stoddart) are most important. Others such as hydrophobic effects have also been utilized. Besides
an interest in molecular topology and the creation of very special and beautiful geometric arrangements
of molecules, the development of artificial molecular machines based on rotaxanes has been a major
driving force for researchers to develop these sythetic strategies and study the properties of rotaxanes
(see for example the special June issue of Acc. Chem. Res., 2001, 34).
We were interested in the problem of the dynamic behaviour of rotaxanes and approached this question by determining the kinetic parameters of the deslipping reaction of a series of rotaxanes with stoppers of intermediate sizes. Heating the rotaxanes to temperatures between 40o and 150o makes the deslipping reaction fast enough to follow it within reasonable time spans. Nevertheless, the synthesis and purification at room temperature is possible.
The scheme below presents results for two rather similar rotaxanes and demonstrates the deslipping kinetics to be very sensitive to even very small structural changes. The two rotaxanes with identical axles differ merely with respect to the wheel, in which a CH group of one of the isophthalic acid building blocks has been replaced by an isoelectronic N atom to yield a wheel bearing a pyridine dicarboxylic acid subunit. This seemingly minor change causes an increase in the activation enthalpy from ca. 80 to 130 kJ/mol. The half-life at 60o increases from ca. 60 hours to more than 1 million hours (extrapolated from measurements at higher temperatures).
This effect can be explained by intramolecular hydrogen bonding within the wheel. The pyridine nitrogen not only fixes the conformation of the pyridine dicarboxylic amide unit so that the two amide hydrogens are pointing into the cavity of the wheel. It also reduces the flexibility of the wheel, which then cannot adjust as easily to the requirements of the transition state. Furthermore, according to molecular modeling results, the wheel shrinks significantly in size. The distance between the two amide nitrogen atoms of the pyridine dicarboxylic amide unit is 10% smaller than that of the corresponding isophthalic amide. Other surprising effects result from variations of the stoppers and the axle center pieces.
The smallest structural change is isotopic substitution. In order to evaluate how sensitive the deslipping reaction is, the deuterated rotaxane shown below was synthesized (together with a second analogue bearing a longer axle) and its deslipping reaction compared to that of its non-deuterated analogue. Indeed, an easily measurable kinetic isotope effect was found. Since the deuterated stoppers are somewhat smaller than the non-labeled ones, the deuterated rotaxanes deslip faster than the non-deuterated ones. The fact that the inverse, secondary isotope effect of ca. 0.9 is temperature insensitive over a range of ca. 60 degrees, permits to conclude that it is mainly the vibrational amplitude which makes the deuterated stoppers appear smaller than the unlabeled analogues.
Another interesting topic related with rotaxanes is their mechanical bond, which guarantees that the two components are free to move relative to each other to a large extent, but cannot dissociate completely without breaking a covalent bond in one of the subunits. Consequently, rotaxanes have interesting mechanical features and it is intriguing to gain control over the motion of their subunits through the action of external stimuli. Such rotaxanes are often called "molecular machines" although they are far from real machines at the molecular level, because they don't drive any process by consuming energy.
Recently, we synthesized the rotaxane shown below (crystal structure shown on the right) and examined its motional properties. The central phenol group can be deprotonated by addition of bases and thus should influence the motion of the wheel. This change should be reversed upon reprotonation of the phenolate. By temperature-dependent NMR and EXSY experiments, two motions were detected in both protonation states: rotation of the wheel around the axle and shuttling of the wheel along the axle between the two identical stations on each arm of the axle. The shuttling rate depends on the protonation state. When deprotonated, the counterion is located close to the central phenolate and thus represents an obstacle for the wheel shuttling. Consequently, deprotonation does not shut down the shuttling completely, but reduces the rate significantly. Since the interactions between cation and phenolate depend on the solvation power of the solvent, the shuttling rate of the deprotonated state can be fine tuned by changing the solvent mixture from unpolar (dichloromethane, slow shuttling) to polar (ca. 20% of DMSO in dichloromethane, fast shuttling). For the first time, a modulation of the mechanical motion between fast and slow has been performed with an external signal.
