Dissipative Catalysis with a Molecular Machine

Abstract We report on catalysis by a fuel‐induced transient state of a synthetic molecular machine. A [2]rotaxane molecular shuttle containing secondary ammonium/amine and thiourea stations is converted between catalytically inactive and active states by pulses of a chemical fuel (trichloroacetic acid), which is itself decomposed by the machine and/or the presence of additional base. The ON‐state of the rotaxane catalyzes the reduction of a nitrostyrene by transfer hydrogenation. By varying the amount of fuel added, the lifetime of the rotaxane ON‐state can be regulated and temporal control of catalysis achieved. The system can be pulsed with chemical fuel several times in succession, with each pulse activating catalysis for a time period determined by the amount of fuel added. Dissipative catalysis by synthetic molecular machines has implications for the future design of networks that feature communication and signaling between the components.


S2. General Experimental
Unless stated otherwise, reagents were obtained from commercial sources and used without purification. Anhydrous solvents were obtained by passing the solvent through an activated alumina column on a Phoenix SDS (solvent drying system; JC Meyer Solvent Systems, CA, USA). Compounds S1 [1] , S2 [1] , (3,5-di-tert-butyl)benzylamine [2] and S9 [3] were synthesized as previously described. 2-Phenylnitroethane 5 is commercially available and spectral data was in line with commercial samples. 1

S4
To a slowly stirred mixture of (3,5-di-tert-butyl) benzylamine (0.61 g, 2.8 mmol) and activated 4 Å molecular sieves (2.8 g) in anhydrous CH 2 Cl 2 (22 mL) was added compound S3 (1.0 g, 2.79 mmol) in CH 2 Cl 2 (6 mL) at RT. The reaction was stirred for 24 h at RT, after which the reaction mixture was filtered through a pad of celite and concentrated under reduced pressure. The crude product mixture was redissolved in MeOH (25 mL) and sodium borohydride (284 mg, 7.51 mmol) was added portionwise at 0 °C. The resulting slurry was stirred at 0 °C for 1.5 h, followed by

S5
To a solution of compound S4 (339 mg, 0.60 mmol) in anhydrous CH 2 Cl 2 (12 mL) was added trifluoroacetic acid (3.0 mL) at RT under N 2 . The reaction mixture was stirred for 2 h, then toluene (6 mL) was added and the solvent removed under reduced pressure.
The crude mixture was redissolved in CH 2 Cl 2 (20 mL) and washed with sat. aq. NaHCO 3 solution (3 x 20 mL), followed by brine (20 mL). The organic phase was dried with MgSO 4 , filtered and concentrated to obtain the product as a yellow oil (242 mg, 91%

S4.1. Stability and fatigue resistance experiments
The long-term stability and fatigue resistance of the molecular shuttle over many pulses of the chemical fuels was tested by mixing compound 1 in toluene-d 8 , then adding pulses of Cl 3 CCO 2 H (1.0 equiv), allowing the system to relax back to equilibrium between each pulse. Figure S1 shows partial 1 H NMR specta of the system measured before and after each of the first seven pulses (spectra in Figure S1 recorded at intervals of 24-36 h from pulse addition to measured spectra). Aside from the emergence of CHCl 3 , no changes could be seen in the spectra. The system hence showed no degradation after any of the pulses, indicating high switching fidelity. Figure S1. Partial 1 H NMR spectra (toluene-d8) demonstrating stability of the rotaxane 1 after seven fuel cycles. S13

S4.2. Nitrostyrene reduction rates
The reaction between 3 and 4 was monitored in the absence and presence of a range of additives to determine the effects of auxiliary system components on the dissipative catalysis. The results are displayed in Figure S2, demonstrating the kinetic profiles of reaction rate in the presence of H-bonding catalyst S9, base, acid and combinations thereof over the first 20-24 h of the reaction.  The evolution of product 5 from reactants 3 and 4 with both the OFF-and ON-state catalysts were tested as controls as shown in Figure S3. ON-state catalyst is approximately sixfold more active than OFF-state.

S4.3.2. Catalysis with thread 2H +
The catalytic ability of the free thread 2H + was also evaluated ( Figure S4). As can be seen from the figure, rate profiles of the free thread and the ON-state catalyst show high similarity.
This corroborates the finding that the catalytic activity of the system decreases significantly when the thiourea unit is encircled by the macrocycle.

S4.3.3. Pulsed catalysis experimental details
For all catalysis experiments, the background reaction rate between compounds 3 and 4 to produce product 5 is relatively fast. The most illustrative way to describe the effects of the fuel pulses on the system was thus deemed to be by use of differential yield profiles, i.e. the difference in product concentration (i.e. yield) between a pulsed and an unpulsed run at any given time. To account for the background reaction with the catalyst present in the OFFstate, an identical reaction to the pulsed run was conducted for 24 h with only the inactivated OFF-state catalyst 1 and the rate constant was extracted assuming 2 nd degree reaction rate  Figure S5). This allowed an artificial background to be simulated to match the time points recorded during the pulsed (using the precise reactant stochiometry from the experiment in question), with the artificial background concentration value then being substracted. Error bars stem from the sensitivity on the NMR measurements and integration (±2.5%, times two for the background-substracted measurements). Note that the reactions seem to suffer from rate retardation over time, potentially due to product inhibition. This means the artificial background approximation breaks down at longer reaction times. Despite this, it was possible to keep adding fuel pulses beyond the three pulses shown in Figure 3c. A further two pulses could be added with visible effects (slope changes in the reaction profiles upon pulse addition, yield evolution ca 2% extra for pulse four and 1.5% for pulse 5) before no effects upon pulse addition were observed.