Entropy-driven translational isomerism: a tristable molecular shuttle.

Abstract

Stimuli-responsive molecular shuttles translocate a macrocycle between different sites (“stations”) on a rotaxane thread under the influence of an external trigger. In bistable shuttles the relative macrocycle binding affinities of the stations are reversed by the stimulus, generally through it bringing about a chemical change in the molecule that targets the enthalpy of binding of the macrocycle to one or both stations. Immediately following the chemical transformation the molecule is no longer in the most energetically favored co-conformation and the macrocycle moves along the thread to its newly preferred position through biased Brownian motion as the system relaxes to the global minimum. Although many external stimuli can be used to induce shuttling in this way, for example pH change, light, and electrochemistry , a simple temperature change is not generally considered one of them. The Boltzmann distribution of the macrocycle between the different binding sites within a shuttle ensures that heating or cooling changes the degree of discrimination the macrocycle expresses for the various stations, but not the actual station preference of the macrocycle. However, a change of relative-station binding affinity with temperature is possible in principle, since DGbinding=DHbinding TDSbinding. If the entropy terms are sufficiently different then the relative binding affinity of the macrocycle for the two stations can be reversed by increasing or lowering the temperature. Here we describe an example of this phenomenon. The [2]rotaxane 1 is, in fact, a tristable molecular shuttle; the first rotaxane in which a ring can be switched between three different positions on a thread (Figure 1). Rotaxane E-1 was prepared in 32% yield from thread E-2 (Scheme 1). E-2 has previously been utilized as the thread for a lightand heat-switchable bistable molecular shuttle 3, and contains two sites designed to hydrogen bond to a benzylic amide macrocycle, namely a fumaramide group (shown in green) and a succinic amide ester unit (orange), separated by a dodecane chain (purple). Shuttle 1 differs from 3 only in that the macrocycle contains endo-pyridine units instead of isophthalamide groups. Photoisomerization of E-1 at 254 nm afforded the cis-rotaxane Z-1 in 54% yield. Since the xylylene units of the macrocycle shield the encapsulated regions of the thread, the position of the ring in Eand Z-1 could be determined by comparing the chemical shift of the protons in the [2]rotaxanes with those of the corresponding threads (Figure 2). The H NMR spectra (400 MHz, 298 K; Figure 2a and b, see page 5888) confirm the position of the macrocycle over the fumaramide station of E-1 in CDCl3. The olefin protons Hi and Hj are shielded by more than 1.5 ppm in the rotaxane relative to the thread, while the chemical shifts of the succinic amide ester protons Hc and Hd are unchanged. Lowering the temperature had no effect on the chemical-shift values, the only significant change in the spectra being that the macrocycle HE protons sharpen as the ring pirouetting about the thread becomes slow on the NMR timescale. In Z-1, the strong binding fumaramide station is replaced with a group of much poorer macrocycle-binding affinity (maleamide) and we expected the macrocycle to be displaced to the succinic amide ester site on the thread (that is, coconformer succ-Z-1), as occurs with Z-3. Whilst the chemical-shift differences (> 1.2 ppm, COSY) of the Hc and Hd protons confirm that this is largely the case [10] at room temperature and above (e.g., at 308 K; Figure 2d), to our surprise the H NMR spectrum of Z-1 proved highly temperature dependent. Indeed, at 258 K (Figure 2e) the major signals for Hc andHd ofZ-1 appear at the same chemical shifts as they do in the thread (Z-2). In addition the olefin protons Hi’ and Hj’ are also unchanged indicating that the macrocycle is not primarily located over either of the designed stations! In fact, it is the alkyl protons of the C12 chain that experience significant upfield shifts (up to 1 ppm at 258 K), which indicates that the pyridine macrocycle is actually positioned Figure 1. Macrocycle translation in a tristable molecular shuttle. Macrocycle movement between 1) and 2) is an entropy-driven process involving no change to the covalent structure of the molecule.