A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

A two-station [2]catenane containing a large macrocycle with two different recognition sites, one bis(pyridinium)ethane and one benzylanilinium, as well as a smaller DB24C8 ring was synthesized and characterized. 1H NMR spectroscopy showed that the DB24C8 ring can shuttle between the two recognition sites depending on the protonation state of the larger macrocycle. When the aniline group is neutral, the DB24C8 ring resides solely at the bis(pyridinium)ethane site, while addition of acid forms a charged benzylanilinium site. The DB24C8 then shuttles between the two charged recognition sites with occupancy favoring the bis(pyridinium)ethane site by a ratio of 4:1. The unprotonated [2]catenane has a deep yellow/orange color when the DB24C8 ring resides solely at the bis(pyridinium)ethane site and changes to colorless when the crown ether is shuttling (i.e., circumrotating) back and forth between the two recognition sites thus optically signalling the onset of the shuttling dynamics.

In addition, we have also previously prepared a [3]catenane containing two dibenzo [24]crown ether DB24C8 rings interlocked onto a much larger macrocyclic ring containing two 1,2bis(pyridinium)ethane recognition sites linked by terphenyl spacer groups [17] (Figure 2).  [2]rotaxane molecular shuttles with both bis(pyridinium)ethane and benzylanilinium recognition sites that can be switched by acid-base chemistry and optically sensed by a) a color change from colorless to yellow and b) a change in fluorescence from OFF to ON (CD 3 CN or CD 2 Cl 2 ). Code: F to indicate CF 3 groups; A to indicate anthracene group. It was thus of interest to design and build these two different recognition sites (benzylanilinium and bis(pyridinium)ethane) into an analogous circumrotational [2]catenane molecular switch to compare to the linear [2]rotaxane molecular shuttles outlined in Figure 1. This should be possible because of the structural similarities (size and shape) between the bis(pyridinium)ethane and benzylanilinium recognition sites. Each has a two-atom chain in a low energy, anti-conformation linking aromatic rings and the distance between the terminal nitrogen atoms are 18.11 and 18.09 Å (MM3) for the benzylaniline and bis(dipyridinium)ethane axles 4 and 5 2+ , respectively; see Figure 2 and Scheme 1 compound [8 DB24C8] 6+ for this comparison and concept.

Synthesis
Although the previously reported [3]catenane ( Figure 2) was synthesized using a one-step, self-assembly procedure from two bis(pyridinium)ethane axles, two terphenyl spacers and two DB24C8 crown ethers, a [2]catenane with different recognition sites requires a stepwise approach involving the incorporation of each recognition site independently. Overall, the synthesis of [2]catenane [8 DB24C8] 6+ required multiple steps and is outlined in Scheme 1. Two literature preparations were used to construct each of the known compounds, terphenyl linker 6 [18] and bis(pyridinium)ethane axle [5][OTf] 2 [19,20], while the new benzylaniline axle 4 was prepared as shown from 3 [21].
To isolate the pure [2]catenane, the reaction solvent (CH 3 CN) was evaporated and the residue washed with toluene to remove excess crown ether. This was then followed by column chromatography on silica gel using a 5:3:2 mixture of CH 3

Characterization
The 1 H NMR spectrum of [2]catenane [8 DB24C8] 6+ (298 K, CD 2 Cl 2 ) is shown in Figure 3 and the labelling scheme for the H-atoms is given in Scheme 1. All resonances were assigned based on 2D COSY NMR spectroscopy as well as comparison to 1 H NMR and COSY spectra of individual components 6 and 7 4+ . Comparing the proton chemicals shifts for H-atoms n-y of [8 DB24C8] 6+ with those of precursor 7 4+ shows changes in chemical shift typically associated with the close interaction of DB24C8 with a bis(pyridinium)ethane recognition site [18]. In particular, the significant downfield shifts observed for ethylene protons s and t from 5.30 ppm in 7 4+ to 5.56 ppm for [8 DB24C8] 6+ as well as u and r, the ortho pyridinium protons, from 9.04 ppm in 7 4+ to 9.31 ppm for [8 DB24C8] 6+ are characteristic of hydrogen-bonding to the crown ether. In addition, π-stacking interactions induce upfield shifts for protons p, q, v and w from 8.48 ppm in 7 4+ to 8.24 ppm for [8 DB24C8] 6+ . Protons o, x, n and y do not shift appreciably because the crown ether does not extend far enough to interact with these protons. In contrast, the chemical shifts for protons a-d and I-L on the benzylaniline portion of the large ring of [8 DB24C8] 6+ do not shift significantly inferring that in the neutral aniline state the crown ether resides exclusively at the bis(pyridinium)ethane site of the [2]catenane. Table 1

Acid-base driven switching
The analysis of the 1 H NMR spectrum (CD 3 CN, 298 K) of [8 DB24C8] 6+ indicates that the DB24C8 ring resides exclusively at the bis(pyridinium)ethane recognition site. This is  ring prefers to occupy the bis(pyridinium)ethane site over the benzylanilinium site and that shuttling between the two sites is slow on the NMR timescale under these experimental conditions. Addition of base (NEt 3 ) returns the system to its original state and the process can be cycled by repeated addition of acid (CF 3 SO 3 H) and base without significant degradation of the compound as verified by 1 H NMR spectroscopy.
Interestingly, these results are contrary to those observed for the [2]

Conclusion
A two-station circumrotational [2]catenane has been synthesized and its operation described. The system consists of a large macrocycle containing two different recognition sites, one bis(pyridinium)ethane and one benzylanilinium with a single smaller DB24C8 ring that can shuttle between the two recognition sites depending on the protonation state of the larger macrocycle. When the aniline group is neutral, the DB24C8 ring resides only at the bis(pyridinium)ethane site. However, addition of acid activates the benzylanilinium site allowing the ring to shuttle between the two, now competing, recognition sites. It was found that DB24C8 prefers the bis(pyridinium)ethane site over the protonated benzylanilinium site in a ratio of 4:1. This is quite different from similar [2]rotaxane molecular shuttles (Figure 1) where, once protonated, the benzylanilinium  site was preferred (CD 3 CN) and in some cases exclusively (CD 2 Cl 2 ) generating a true ON/OFF bistable switch; unfortunately, the [2]catenane switch is insoluble in CD 2 Cl 2 when protonated so a comparison could not be undertaken in this solvent. This difference in site populations between [2]rotaxane and [2]catenane is due to the presence of electron-withdrawing CF 3 groups on the [2]rotaxane which make the benzylanilinium site more favorable in this case. Since it is fairly straightforward to change the nature of the stoppering groups of a [2]rotaxane dumbbell while the cyclic nature of the large ring makes it difficult to derivatize, [2]rotaxanes are deemed easier to fine-tune from a structural perspective than [2]catenanes. Although we were able to create an optically sensitive [2]catenane molecular shuttle with the bis(pyridinium)ethane and benzylanilinium recognition motifs, we could not achieve the true ON/OFF, bistable molecular switching previously observed for analogous [2]rotaxanes.

Experimental
General comments 4-Bromobenzyl bromide, 4-bromoaniline, 4-pyridylboronic acid, 1,3-dichlorobenzene, p-tolylmagnesium bromide, n-butyllithium and N-bromosuccinimide were purchased from Aldrich and used as received. Benzoyl peroxide was purchased from Acros and used as received. Compounds 3 [18], [5][OTf] 2 [19,20] and 6 [21] were prepared using literature methods. Solvents were dried using an Innovative Technologies solvent purification system. Thin-layer chromatography (TLC) was performed using Teledyne Silica gel 60 F254 plates and viewed under UV light. Column chromatography was performed using Silicycle ultra-pure silica gel (230-400 mesh). The solvents were dried and distilled prior to use. NMR spectra were recorded on a Bruker Avance III console equipped with an 11.7 T magnet (e.g., 500 MHz for 1 H). Samples were locked to the deuterated solvent and all chemical shifts reported in ppm referenced to tetramethylsilane. Mass spectra were recorded on a Waters Xevo G2-XS instrument. Solutions with concentrations of 0.001 molar were prepared in methanol and injected for analysis at a rate of 5 µL/min using a syringe pump. Synthesis of [7][OTf] 4 [5][OTf] 2 (0.400 g, 0.626 mmol) and 6 (2.61 g, 6.26 mmol) were dissolved in CH 3 CN (75 mL) and stirred at room temperature for 7 days. The resulting precipitate was filtered, collected and stirred in CH 2 Cl 2 for 20 min and filtered to remove excess 6. The precipitate was then anion exchanged to the triflate salt in a two-layer CH 3