A halogen- and hydrogen-bonding [2]catenane for anion recognition and sensing

Abstract

A mixed halogen- and hydrogen-bonding hetero-[2]catenane has been synthesised via an anion templated Grubbs' II-catalysed RCM clipping mechanical bond forming methodology. ¹H NMR spectroscopy and fluorescence titration experiments demonstrated the interlocked catenane host to be capable of binding and sensing anions, in particular forming strong associations with acetate and dihydrogen phosphate.

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Introduction

The field of anion supramolecular chemistry has become a thriving area of modern research owing to the realisation that anions play crucial roles in numerous biological, environmental, chemical and medicinal processes.^1–6 Consequently, a vast array of anion receptors have been reported in the literature that employ numerous non-covalent interactions such as electrostatics, hydrogen bonding (HB), Lewis acid–base,⁷ and anion–π^8–10 bonding to bind anionic guests.^11,12 Despite these efforts, the challenge of raising the degree of recognition to that of biotic systems still remains and we have attempted to meet this challenge via the construction of interlocked host molecules that contain uniquely preorganised, three-dimensional binding cavities.¹³

Halogen bonding (XB) is the attractive, highly directional, non-covalent interaction between an electron-deficient halogen atom and a Lewis base.¹⁴ Despite its comparable strength to hydrogen bonding and stringent directionality, the utilisation of halogen bonding for solution phase applications such as molecular recognition, catalysis and medicinal chemistry^15–17 is still very much in its infancy, with previous attention focusing mainly on solid state crystal engineering.^18–24 In an attempt to further the field of halogen bonding anion recognition, we have prepared the first halogen bonding rotaxane structures which exhibit impressive halide anion recognition behaviour in aqueous solvent mixtures of up to 50% water.^25–27 Furthermore halogen bond bromoimidazolium^28,29 and bromo- and iodo-pyridinium donor groups of catenane hosts³⁰ have been recently shown to selectively bind halides.

Herein, we describe the synthesis of a novel XB-HB iodo-triazolium functionalised hetero-[2]catenane host and investigate its anion recognition and sensing properties.

Results and discussion

Initial synthetic efforts centred on integrating the XB iodo-triazolium motif into a bis-vinyl functionalised macrocycle precursor compound 14·Cl. This was anticipated to be able to interpenetrate a HB isophthalamide containing macrocycle 15, in the presence of a templating anion, affording the target XB-HB hetero-catenane via a clipping Grubbs' II-catalysed ring closing metathesis (RCM) mechanical bond forming reaction.

XB macrocyclic precursor synthesis

The preparation of bis-vinyl appended iodo-triazolium precursor compound 14·Cl was achieved via the multistep synthetic pathways shown in Schemes 1–3. Azide 7 and iodo-alkyne 12 functionalised vinyl derivatives were prepared initially for subsequent copper(I) catalysed azide alkyne cycloaddition (CuAAC) click reaction to form the bis-vinyl iodo-triazole intermediate compound 13.

Scheme 1 Synthesis of vinyl appended azide compound 7.

Scheme 2 Synthesis of vinyl appended iodo-alkyne 12.

Scheme 3 Synthesis of iodo-triazolium containing bis-vinyl appended precursor 14·Cl.

2,7-Dihydroxynaphthalene was reacted with two equivalents of ethyl bromoacetate, in the presence of K₂CO₃ to form compound 1 (68%), which was then converted to diol 2 in 67% yield by reduction with lithium aluminium hydride in dry THF (Scheme 1). Reaction of 2 with methanesulfonyl chloride and triethylamine in dry THF afforded bis-mesylate 3 in 59% yield. The reaction of one equivalent of mesylate 4 with hydroquinone under basic conditions afforded the mono-functionalised derivative 5 in 60% yield. An equimolar reaction of 5 and bis-mesylate 3, in the presence of K₂CO₃, in dry acetonitrile gave 6 (34%). Reaction of 6 with sodium azide resulted in the formation of azide compound 7 in 91% yield.

Iodo-alkyne 12 was prepared by the route shown in Scheme 2. The previously isolated mono-functionalised hydroquinone 5 was reacted with bis-tosylate 8 to form compound 9 (53%). This was then reacted with the product 10 of a Mitsunobu reaction between 2,7-dihydroxynaphthalene and 3-butyn-1-ol to form alkyne 11 in 42% yield. Reaction of 11 with N-iodosuccinimide, in the presence of a catalytic amount of AgNO₃, afforded the desired iodo-alkyne 12 (80%).

The iodo-triazolium containing bis-vinyl appended precursor 14·Cl was then synthesised by a two-step procedure from azide 7 and iodo-alkyne 12 (Scheme 3). ‘Click’ reaction³¹ of 7 and 12 afforded the bis-vinyl appended iodo-triazole compound 13 in 79% yield. Methylation with (Me₃O)BF₄ in dry CH₂Cl₂ gave the tetrafluoroborate salt 14·BF₄ (94%), which was dissolved in chloroform and anion exchanged to the corresponding chloride salt 14·Cl by repeated washing with 1 M NH₄Cl_(aq) (92%).

Pseudorotaxane investigation

We have previously shown a simple bis-hexyl substituted iodo-triazolium functionalised threading species to be capable of forming a [2]pseudorotaxane with an isophthalamide macrocycle via halide anion templation.²⁵ With this in mind, it was hoped that iodo-triazolium containing bis-vinyl appended precursor 14·Cl would form an interpenetrated assembly with a similar isophthalamide macrocycle, which could ultimately be cyclised to form the target [2]catenane.

Initially, a qualitative equimolar ¹H NMR titration experiment was performed to ascertain if there was any evidence for interpenetrative pseudorotaxane formation between 14·Cl and isophthalamide macrocycle 15.³² Upon addition of one equivalent of 14·Cl to a CD₂Cl₂ solution of macrocycle 15, the macrocycle hydroquinone protons δ and ε shifted upfield and split, which is diagnostic of an interpenetrative assembly (Fig. 1). Also, downfield shifts of the macrocycle isophthalamide protons α and β arising from hydrogen bonding with the templating chloride anion were noted. Finally, the signals corresponding to the naphthalene and hydroquinone protons of 14·Cl split, indicating that it was threading the macrocycle.

Fig. 1 Truncated ¹H NMR spectra of (a) 14·Cl, (b) an equimolar mixture of 14·Cl and isophthalamide macrocycle 15 and (c) isophthalamide macrocycle 15 (500 MHz, CD₂Cl₂, 293 K).

Catenane synthesis

The novel catenane was prepared by reaction of one equivalent of 14·Cl and 1.5 equivalents of macrocycle 15, in dry CH₂Cl₂, with Grubbs' II catalyst (Scheme 4). The product was isolated as its chloride salt 16·Cl in 6% yield after challenging purification via preparative thin layer chromatography. Repeated washing of a chloroform solution of 16·Cl with 0.1 M NH₄PF_6(aq) afforded the hexafluorophosphate salt of the catenane 16·PF₆ (84%). It is noteworthy that when the catenane synthesis was repeated in the absence of chloride, with 14·BF₄, no evidence of catenane formation was detected by ESI-MS, which highlights the crucial templating effect of the halide anion. The low yield of 16·Cl is likely due to the competing intramolecular cyclisation of 14·Cl, as evidenced by a mass peak corresponding to the ring closed form of 14⁺ in the ESI-MS spectrum of the crude reaction mixture (see ESI, S2†).

Scheme 4 Synthesis of XB-HB catenane 16·PF₆.

The new catenane 16·Cl was characterised by ¹H NMR and high resolution ESI mass spectrometry. High resolution ESI-MS analysis of 16·Cl gave the expected mass peak at m/z 1588.5346 [M − Cl]⁺ and the ¹H NMR spectrum of 16·Cl, together with those of precursor 14·Cl and macrocycle 15, is shown in Fig. 2. It can be seen that upon catenane formation the macrocycle protons α, β and κ are all shifted downfield, with this attributed to hydrogen bonding with the templating chloride anion.

Fig. 2 Truncated ¹H NMR spectra of (a) macrocycle 15, (b) catenane 16·Cl and (c) iodo-triazolium containing bis-vinyl appended precursor 14·Cl (500 MHz, CDCl₃, 293 K, for atom labels see Scheme 4).

Importantly, the macrocycle hydroquinone protons δ and ε have shifted upfield and split due to aromatic donor–acceptor interactions with the electron-deficient iodo-triazolium motif indicative of interlocked structure formation, with this ratified further by the presence of a peak corresponding to the alkene protons i of the closed threading component. The naphthalene region of the catenane's ¹H NMR spectrum is complex due to the asymmetric nature of the iodo-triazolium macrocycle component (see ESI, S3†).

The interlocked nature of 16⁺ was confirmed by two-dimensional ¹H–¹H ROESY NMR, with a number of through space couplings observed between the isophthalamide and iodo-triazolium macrocycle components (Fig. 3).

Fig. 3 Truncated ROESY NMR spectrum of catenane 16·Cl (500 MHz, CDCl₃, 293 K, for atom labels see Scheme 4).

Anion recognition and sensing properties

A comparison of the ¹H NMR spectra of the chloride and hexafluorophosphate salts of the catenane 16⁺, revealed perturbations of a number of protons indicative of halide anion binding (Fig. 4). Downfield shifts of protons α, β and κ of the isophthalamide macrocycle component are a result of hydrogen bonding interactions with the chloride anion. In addition, naphthalene protons e, e′, f, f′ also shift downfield revealing they are also involved in anion binding. Hydroquinone protons δ and ε are seen to move upfield possibly as a result of chloride anion complexation leading to a catenane conformation with enhanced aromatic donor–acceptor interactions between the electron-rich isophthalamide macrocycle hydroquinone groups and the electron-deficient iodo-triazolium motif.

Fig. 4 Truncated ¹H NMR spectra of (a) 16·Cl and (b) 16·PF₆ (500 MHz, CDCl₃, 293 K, for atom labels see Scheme 4).

Exploiting the naphthalene groups of catenane 16·PF₆ allowed for fluorescence anion titration experiments to be performed, in acetonitrile solution. Increasing amounts of the TBA salts of chloride, bromide, iodide, acetate (Fig. 5) and dihydrogen phosphate were added to separate acetonitrile solutions of 16·PF₆ and the naphthalene fluorescence emission spectra monitored (see ESI, S5† for additional spectra).

Fig. 5 Changes in the emission spectrum of catenane 16·PF₆ in acetonitrile upon addition of increasing amounts of TBA·OAc ([host] = 1 × 10⁻⁵ M, λ_exc = 280 nm, 293 K).

In all cases, increases in intensity of the naphthalene monomer emission bands (326 and 340 nm) were observed upon the addition of anions, concomitant with a decrease in intensity of the catenane's broad excimer³³ emission band (centred at 410 nm). The relative magnitudes of these changes after the addition of 20 equivalents of anion are shown in Table 1 and represented graphically in Fig. 6. Analogous UV-visible spectroscopy anion titration experiments revealed no changes in the absorption spectrum of the catenane. As a consequence of the high degree of preorganisation of the catenane host, the electronic and structural changes that occur upon anion complexation are relatively small. The high sensitivity of the fluorescence technique makes it possible to detect these small changes, whereas UV-visible spectroscopy is considerably less sensitive and no absorption spectral perturbations were observed.

Table 1 Percentage changes in emission intensity, ΔI (%), at 326, 340 and 410 nm after the addition of 20 equivalents of various anions to an acetonitrile solution of catenane 16·PF₆ ([host] = 1 × 10⁻⁵ M, λ_exc = 280 nm, 293 K)

Anion	326 nm	340 nm	410 nm
Cl^−	+28	+29	−20
Br^−	+12	+13	−23
I^−	+7	+4	−36
OAc^−	+66	+73	−14
H2PO4^−	+56	+58	−7

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Fig. 6 Graphical representation of the anion induced percentage changes in emission intensity data reported in Table 1.

The observed increases in intensity of the monomer emission bands are thought to be a result of the rigidity effect, which arises from anion complexation reducing the number of available vibrational and rotational non-radiative decay processes.³⁴ The addition of acetate and dihydrogen phosphate induced much greater percentage increases in emission intensity than the halides, which tentatively suggests the catenane 16·PF₆ binds the oxoanions the most strongly. The decrease in excimer emission may be attributed to anion binding preventing intramolecular excimer formation, as the guest would bind in the host cavity between the two naphthalene groups. The most dramatic decrease is observed with iodide, which is likely to be augmented by the effects of heavy atom collisional quenching.³⁵

It was hoped that monitoring the intensity of the monomer emission bands of 16·PF₆ upon the addition of anions would provide titration data from which anion association constants could be determined. DynaFit³⁶ analysis of the titration data, however, was only able to calculate 1 : 1 stoichiometric association constants for acetate and dihydrogen phosphate binding (Fig. 7 and Table 2).³⁷

Fig. 7 Changes in monomer emission intensity upon addition of increasing amounts of acetate and dihydrogen phosphate anions, as their TBA salts, to separate acetonitrile solutions of catenane 16·PF₆ ([host] = 1 × 10⁻⁵ M, λ_exc = 280 nm, 293 K, data points represent experimental data, continuous lines represent calculated curves).

Table 2 Association constants, K_a (M⁻¹), for catenane 16·PF₆ with acetate and dihydrogen phosphate anions (CH₃CN, 293 K)

Anion	Ka^a (M^−1)
a 99% confidence intervals given in square brackets, a 1 : 1 binding model was used in all cases.
OAc^−	1.5 × 10^5 [1.3 to 1.8 × 10^5]
H2PO4^−	4.5 × 10^4 [4.1 to 4.8 × 10^4]

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Catenane 16·PF₆ binds acetate and dihydrogen phosphate strongly in acetonitrile solution with a preference for the former more basic oxoanion. Interestingly, this strong oxoanion recognition is in contrast to a previously reported bromo-imidazolium functionalised catenane,²⁹ which exhibited chloride anion selectivity and did not detect these oxoanions via analogous fluorescence titration experiments in the same solvent.²⁹

Conclusions

A novel [2]catenane 16·PF₆, containing both halogen- and hydrogen-bonding macrocyclic components, was successfully isolated via an anion templated Grubbs' II-catalysed RCM clipping mechanical bond forming methodology. Preliminary ¹H NMR studies revealed the catenane bound chloride and fluorescence anion titration experiments were undertaken in an effort to quantitatively assess the interlocked host's anion binding properties. Notable fluorescence responses were observed upon the addition of various anions to an acetonitrile solution of 16·PF₆, with the largest perturbations of emission intensity occurring with acetate and dihydrogen phosphate. Dynafit³⁶ analysis of the titration data revealed that both oxoanions were bound strongly by the catenane host.

Experimental

General remarks

All reagents and solvents were purchased from commercial sources and used without further purification. Where necessary, solvents were dried by passing through a MBraun MPSP-800 column and degassed with nitrogen. Water was de-ionised and microfiltered using a Milli-Q® Millipore machine. NEt₃ was distilled and stored over KOH. All TBA salts, Grubbs' II catalyst and TBTA were stored in vacuum desiccators prior to use. Column chromatography was performed on silica gel (particle size: 40–63 μm), preparative TLC was performed on 20 × 20 cm plates with a silica layer thickness of 1 mm.

NMR spectra were recorded on either a Varian Mercury 300 or Varian Unity Plus 500 spectrometer and high resolution mass spectra were obtained using a Bruker MicroTOF spectrometer. ¹H and ¹³C NMR spectra of novel compounds, fluorescence titration protocols and additional fluorescence titration spectra can be found in the ESI.†

Compounds 1,³⁸ 2,³⁸ 3,³⁸ 4,³⁹ 5,⁴⁰ 8 ⁴¹ and 15 ³² were prepared as previously reported.

Vinyl-appended mesylate (6)

4-(2-(Allyloxy)ethoxy)phenol 5 (480 mg, 2.47 mmol) and K₂CO₃ (1.88 g, 13.6 mmol) were stirred in dry MeCN (100 mL) for 20 minutes. After this time, compound 3 (2.00 g, 4.94 mmol) was added and the reaction mixture refluxed overnight under nitrogen. The mixture was then cooled, filtered and the solvent removed to give the crude product, which was purified via silica gel column chromatography (99 : 1 CH₂Cl₂–MeOH) to give 6 as an off-white solid (0.429 g, 34%). ¹H NMR (300 MHz, CDCl₃): δ 7.73–7.66 (m, 2H, ArH), 7.11–6.98 (m, 4H, ArH), 6.94–6.86 (m, 4H, ArH), 6.03–5.88 (m, 1H, –CH=CH₂), 5.37–5.19 (m, 2H, –CH=CH₂), 4.68–4.62 (m, 2H, –CH₂), 4.44–4.31 (m, 6H, –CH₂), 4.13–4.06 (m, 4H, –CH₂), 3.80 (t, ³J = 5.0 Hz, 2H –CH₂), 3.13 (s, 3H, –CH₃). ¹³C NMR (75 MHz, CDCl₃): δ 134.5, 129.5, 129.2, 124.7, 117.3, 116.8, 115.7, 115.6, 106.3, 72.3, 68.6, 68.0, 67.1, 66.5, 65.7, 37.8. HRMS (ESI +ve) m/z: 525.1568 ([M + Na]⁺, C₂₆H₃₀NaO₈S requires 525.1554).

Vinyl-appended azide (7)

Compound 6 (233 mg, 0.464 mmol) was dissolved in dry DMF (50 mL) before NaN₃ (151 mg, 2.32 mmol) was added and the mixture heated at 85 °C overnight. After this time, the reaction mixture was cooled to room temperature and the solvent removed in vacuo. The resultant solid was then taken up in Et₂O (50 mL) and washed with water (2 × 40 mL) and brine (2 × 40 mL) before being dried (MgSO₄) and filtered. The solvent was then removed to give 7 as an off-white solid (190 mg, 91%). ¹H NMR (300 MHz, CDCl₃): δ 7.74–7.64 (m, 2H, ArH), 7.13–7.01 (m, 4H, ArH), 6.95–6.85 (m, 4H, ArH), 6.05–5.88 (m, 1H, –CH=CH₂), 5.37–5.18 (m, 2H, –CH=CH₂), 4.41 (t, ³J = 5.1 Hz, 2H, –OCH₂CH₂OPh), 4.34 (t, ³J = 5.3 Hz, 2H, –CH₂OPh), 4.27 (t, ³J = 5.1 Hz, 2H, –CH₂CH₂OCHCH₂), 4.14–4.06 (m, 4H, –OCH₂CH₂N₃ & –OCH₂CHCH₂), 3.80 (t, ³J = 4.9 Hz, 2H, –CH₂OCHCH₂), 3.67 (t, ³J = 4.9 Hz, 2H, –CH₂N₃). ¹³C NMR (75 MHz, CDCl₃): δ 135.6, 134.5, 129.3, 129.2, 124.7, 117.4, 116.6, 116.2, 115.7, 106.3, 72.3, 68.6, 68.0, 67.1, 66.8, 66.5, 50.1. HRMS (ESI +ve) m/z: 472.1833 ([M + Na]⁺, C₂₅H₂₇N₃NaO₅ requires 472.1843).

2-(4-(2-(Allyloxy)ethoxy)phenoxy)ethyl-4-methylbenzene sulfonate (9)

Compound 5 (1.29 g, 6.62 mmol) was dissolved in dry MeCN (100 mL) and stirred with K₂CO₃ (6.88 g, 49.8 mmol) for 20 minutes under nitrogen. After this time, bis-tosylate 8 (4.92 g, 13.3 mmol) was added and the reaction mixture heated at 85 °C overnight under nitrogen. The mixture was cooled to room temperature and filtered before the solvent was removed in vacuo. The resultant solid was then suspended in CHCl₃ and filtered to remove the toluenesulfonic acid side product. The solvent was then removed and the crude product purified via silica gel column chromatography (CH₂Cl₂) to give 9 as a pale yellow oil (1.38 g, 53%). ¹H NMR (300 MHz, CDCl₃): δ 7.82 (d, ³J = 8.0 Hz, 2H tosyl ArH), 7.35 (d, ³J = 8.0 Hz, 2H, tosyl ArH), 6.83 (d, ³J = 9.3 Hz, 2H, ArH), 6.72 (d, ³J = 8.9 Hz, 2H, ArH), 6.02–5.87 (m, 1H, –CH=CH₂), 5.36–5.18 (m, 2H, –CH=CH₂), 4.37–4.31 (m, 2H, –CH₂), 4.13–4.05 (m, 8H, –CH₂), 3.81–3.76 (m, 2H, –CH₂), 2.46 (s, 3H, –CH₃). ¹³C NMR (75 MHz, CDCl₃): δ 152.3, 150.2, 134.3, 129.8, 127.8, 115.9, 115.6, 115.5, 72.2, 68.5, 68.3, 68.0, 66.0, 50.4, 21.5. HRMS (ESI +ve) m/z: 415.1188 ([M + Na]⁺, C₂₀H₂₄NaO₆S requires 415.1186).

7-(But-3-yn-1-yloxy)naphthalen-2-ol (10)

2,7-Dihydroxynaphthalene (500 mg, 3.12 mmol), 3-butyn-1-ol (0.237 mL, 3.12 mmol) and PPh₃ (819 mg, 3.12 mmol) were dissolved in dry THF (100 mL) and the solution cooled to 0 °C. DEAD (0.492 mL, 3.12 mmol) was then added dropwise before the reaction mixture was left to stir overnight under nitrogen. After this time, the solvent was removed and the resulting residue stirred in Et₂O (50 mL) to precipitate the triphenylphosphine oxide side product. This was then removed via filtration and the filtrate evaporated to dryness to give an orange oil which was purified by silica gel column chromatography (98 : 2 CH₂Cl₂–MeOH) to yield 10 as a white solid (108 mg, 16%). ¹H NMR (300 MHz, CDCl₃): δ 7.67 (d, ³J = 8.6 Hz, 2H, ArH), 7.07–6.93 (m, 4H, ArH), 4.21 (t, ³J = 7.1 Hz, 2H, –OCH₂), 2.79–2.72 (m, 2H, –OCH₂CH₂), 2.08 (t, ⁴J = 2.6 Hz, 1H, –C≡CH). ¹³C NMR (75 MHz, CDCl₃): δ 157.0, 154.2, 135.8, 129.3, 124.4, 116.3, 115.4, 108.7, 105.7, 69.9, 65.9, 19.5, 14.4. HRMS (ESI −ve) m/z: 211.0763 ([M − H]⁻, C₁₄H₁₁O₂ requires 211.0765).

2-(2-(4-(2-(Allyloxy)ethoxy)phenoxy)ethoxy)-7-(but-3-yn-1-yloxy)naphthalene (11)

Tosylate 9 (0.700 g, 1.78 mmol) and K₂CO₃ (1.85 g, 13.4 mmol) were stirred for 20 minutes in dry MeCN (150 mL) under nitrogen. Compound 10 (0.379 g, 1.78 mmol) was then added and the reaction mixture heated at 85 °C overnight under nitrogen. After cooling to room temperature, the reaction mixture was filtered and the solvent removed in vacuo. The resultant residue was then purified via silica gel column chromatography (CH₂Cl₂) to give alkyne 11 as an off-white solid (326 mg, 42%). ¹H NMR (300 MHz, CDCl₃): δ 7.68 (d, ³J = 9.0 Hz, 2H, ArH), 7.11–7.00 (m, 4H, ArH), 6.94–6.87 (m, 4H, ArH), 6.03–5.88 (m, 1H, –CH=CH₂), 5.36–5.19 (m, 2H, –CH=CH₂), 4.44–4.39 (m, 2H, –CH₂), 4.38–4.32 (m, 2H, –CH₂), 4.22 (t, ³J = 7.1 Hz, 2H, –CH₂), 4.13–4.08 (m, 4H, –CH₂), 3.82–3.77 (m, 2H, –CH₂), 2.80–2.72 (m, 2H, –CH₂C≡CH), 2.08 (t, ⁴J = 2.6 Hz, 1H, –C≡CH). ¹³C NMR (75 MHz, CDCl₃): δ 157.1, 156.9, 153.2, 152.8, 135.6, 134.5, 129.1, 124.5, 117.3, 116.4, 116.2, 115.6, 106.3, 106.2, 80.4, 72.3, 69.9, 68.5, 67.9, 67.0, 66.4, 65.8, 19.4. HRMS (ESI +ve) m/z: 455.1819 ([M + Na]⁺, C₂₇H₂₈NaO₅ requires 455.1829).

Vinyl-appended iodo-alkyne (12)

Alkyne 11 (326 mg, 0.753 mmol) and N-iodosuccinimide (203 mg, 0.903 mmol) were dissolved in acetone (20 mL) and then AgNO₃ (15.3 mg, 0.0903 mmol) was added before the reaction mixture was left to stir overnight, in the dark, under nitrogen. After this time, the reaction mixture was poured into ice water (50 mL) and extracted with CH₂Cl₂ (3 × 50 mL). The combined organic phase was then washed with brine (50 mL), dried (MgSO₄), filtered and the solvent removed to give the crude product. This was then purified via silica gel column chromatography (98 : 2 CH₂Cl₂–MeOH) to give 12 as a white solid (336 mg, 80%). ¹H NMR (300 MHz, CDCl₃): δ 7.67 (d, ³J = 8.9 Hz, 2H, ArH), 7.11–6.98 (m, 4H, ArH), 6.94–6.86 (m, 4H, ArH), 6.03–5.88 (m, 1H, –CH=CH₂), 5.37–5.19 (m, 2H, –CH=CH₂), 4.44–4.38 (m, 2H, –CH₂), 4.38–4.32 (m, 2H, –CH₂), 4.20 (t, ³J = 7.2 Hz, 2H, –CH₂), 4.14–4.07 (m, 4H, –CH₂), 3.80 (t, ³J = 5.0 Hz, 2H, –CH₂), 2.92 (t, ³J = 7.0 Hz, 2H, –CH₂). ¹³C NMR (75 MHz, CDCl₃): δ 157.2, 156.8, 153.3, 152.9, 135.6, 134.5, 129.1, 124.6, 117.3, 116.5, 116.3, 115.7, 106.3, 90.3, 72.3, 68.6, 68.0, 67.1, 66.5, 65.8, 21.7. HRMS (ESI +ve) m/z: 581.0801 ([M + Na]⁺, C₂₇H₂₇INaO₅ requires 581.0795).

Iodo-triazole containing bis-vinyl appended precursor (13)

CuI (2.96 mg, 0.0156 mmol) and TBTA (8.27 mg, 0.0156 mmol) were stirred in dry degassed THF (5 mL) for 20 minutes in the dark under nitrogen. After this time, azide 7 (70.0 mg, 0.156 mmol) and alkyne 12 (87.0 mg, 0.156 mmol), dissolved in dry degassed THF (5 mL), were added to the catalyst solution which was then stirred overnight in the dark under nitrogen. Following this, 10% NH₄OH_(aq) (10 mL) was added to quench the reaction and the volatile components were removed in vacuo. Water (20 mL) was then added to the solution and the product extracted with CH₂Cl₂ (3 × 20 mL). The organic phase was then dried (MgSO₄) and the solvent removed to yield the crude product, which was then purified via silica gel column chromatography (99 : 1 CH₂Cl₂–MeOH) to give 13 as a white solid (124 mg, 79%). ¹H NMR (300 MHz, CDCl₃): δ 7.65 (d, ³J = 6.4 Hz, 2H, ArH), 7.62 (d, ³J = 5.8 Hz, 2H, ArH), 7.08–7.04 (m, 4H, ArH), 7.03–6.95 (m, 4H, ArH), 6.91–6.88 (m, 8H, ArH), 6.03–5.88 (m, 2H, –CH=CH₂), 5.37–5.19 (m, 4H, –CH=CH₂), 4.84 (t, ³J = 5.8 Hz, 2H, naphthalene–OCH₂), 4.53 (t, ³J = 5.6 Hz, 2H, naphthalene–OCH₂), 4.41–4.35 (m, 6H, –CH₂), 4.35–4.30 (m, 4H, –CH₂), 4.12–4.07 (m, 8H, –CH₂), 3.81–3.77 (m, 4H, –CH₂), 3.24 (t, ³J = 7.0 Hz, 2H, triazole–CH₂). ¹³C NMR (75 MHz, CDCl₃): δ 157.3, 157.2, 156.4, 155.3, 153.3, 152.9, 145.8, 135.7, 134.6, 129.3, 129.1, 117.4, 116.4, 115.6, 106.3, 72.4, 68.6, 68.0, 67.2, 66.5. HRMS (ESI +ve) m/z: 1030.2751 ([M + Na]⁺, C₅₂H₅₄IN₃NaO₁₀ requires 1030.2746).

Iodo-triazolium containing bis-vinyl appended precursor tetrafluoroborate salt (14·BF₄)

Iodo-triazole containing bis-vinyl appended precursor 13 (114 mg, 0.113 mmol) was dissolved in dry CH₂Cl₂ (30 mL) before (Me₃O)BF₄ (25.1 mg, 0.170 mmol) was added and the reaction mixture left to stir overnight under nitrogen. After this time, MeOH (10 mL) was added to quench the reaction and the solvent was removed to give a pale orange solid. This was purified via silica gel column chromatography (95 : 5 CH₂Cl₂–MeOH) to give 14·BF₄ as an off-white solid (118 mg, 94%). ¹H NMR (300 MHz, CDCl₃): δ 7.58–7.41 (m, 4H, ArH), 7.11–7.05 (m, 2H, ArH), 7.04–6.94 (m, 4H, ArH), 6.83 (s, 8H, ArH), 6.81–6.76 (m, 2H, ArH), 6.01–5.85 (m, 2H, –CH=CH₂), 5.35–5.16 (m, 4H, –CH=CH₂), 4.80–4.70 (m, 2H, naphthalene–OCH₂), 4.46–4.37 (m, 2H, naphthalene–OCH₂), 4.32–4.25 (m, 4H, –CH₂), 4.25–4.17 (m, 7H, –CH₂ & –CH₃), 4.16–4.10 (m, 2H, –CH₂), 4.10–4.01 (m, 8H, –CH₂), 3.75 (t, ³J = 4.7 Hz, 4H, –CH₂), 3.24–3.14 (m, 2H, triazole–CH₂). ¹³C NMR (75 MHz, CDCl₃): δ 157.3, 156.0, 155.8, 153.2, 152.8, 145.7, 135.5, 134.5, 129.3, 129.1, 124.6, 117.3, 117.0, 115.5, 106.8, 106.5, 106.2, 72.3, 68.5, 68.0, 67.1, 66.6, 38.9. ¹⁹F NMR (283 MHz, CDCl₃): δ –151.9 (d, J = 15.8 Hz). HRMS (ESI +ve) m/z: 1022.3099 ([M − BF₄]⁺, C₅₃H₅₇IN₃O₁₀ requires 1022.3083).

Iodo-triazolium containing bis-vinyl appended precursor chloride salt (14·Cl)

14·BF₄ (70.0 mg, 0.0631 mmol) was dissolved in CHCl₃ (20 mL) and washed with 1 M NH₄Cl_(aq) (10 × 20 mL) and water (20 mL) before being dried (MgSO₄) and filtered. The solvent was then removed to give 14·Cl as an orange solid (61.5 mg, 92%). ¹H NMR (500 MHz, CDCl₃): δ 7.58 (d, ³J = 8.6 Hz, 1H, ArH), 7.53 (d, ³J = 8.6 Hz, 2H, ArH), 7.47 (d, ³J = 8.6 Hz, 1H, ArH), 7.10–7.06 (m, 2H, ArH), 7.05–6.98 (m, 3H, ArH), 6.96–6.93 (m, 1H, ArH), 6.88–6.82 (m, 9H, ArH), 6.78–6.74 (m, 1H, ArH), 5.98–5.89 (m, 2H, –CH=CH₂), 5.34–5.17 (m, 4H, –CH=CH₂), 4.91–4.84 (m, 2H, –CH₂), 4.53–4.47 (m, 2H, –CH₂), 4.38 (s, 3H, –CH₃), 4.37–4.32 (m, 4H, –CH₂), 4.29–4.24 (m, 4H, –CH₂), 4.22–4.16 (m, 2H, –CH₂), 4.10–4.04 (m, 8H, –CH₂), 3.77 (t, ³J = 4.7 Hz, 4H, –CH₂), 3.41–3.35 (m, 2H, triazole–CH₂). ¹³C NMR (126 MHz, CDCl₃): δ 157.3, 155.8, 153.3, 152.9, 145.2, 135.5, 134.5, 129.3, 129.1, 124.6, 117.3, 115.6, 106.9, 106.5, 106.2, 103.3, 72.3, 68.6, 68.0, 67.1, 66.7, 65.1, 64.8, 53.6, 38.9. HRMS (ESI +ve) m/z: 1022.3099 ([M − Cl]⁺, C₅₃H₅₇IN₃O₁₀ requires 1022.3083).

Iodo-triazolium functionalised [2]catenane chloride salt (16·Cl)

Isophthalamide macrocycle 15 (33.7 mg, 0.0567 mmol) and iodo-triazolium containing bis-vinyl appended precursor chloride salt 14·Cl (40.0 mg, 0.0378 mmol) were dissolved in dry CH₂Cl₂ (10 mL) and stirred for 1 hour under nitrogen. Grubbs' II (4.00 mg, 10% by weight) was then added and the reaction mixture left to stir overnight, in the dark, under nitrogen. After this time, the solvent was removed and the crude product purified via preparative TLC (93 : 7 CH₂Cl₂–MeOH) to give 16·Cl as an off-white solid (3.52 mg, 6%). ¹H NMR (500 MHz, CDCl₃): δ 9.40 (s, 1H ArH isophthalamide internal), 8.82–8.74 (m, 2H, –NH), 8.52 (d, 2H, ³J = 7.8 Hz, ArH isophthalamide external), 7.78 (s, 1H, ArH naphthalene internal), 7.76–7.69 (m, 2H, ArH naphthalene external), 7.64–7.58 (m, 3H, ArH naphthalene external & isophthalamide external), 7.39 (s, 1H, ArH naphthalene internal), 7.31 (s, 1H, ArH naphthalene internal), 7.14 (d, ³J = 8.8 Hz, 1H, ArH naphthalene external), 7.09 (d, ³J = 8.8 Hz, 1H, ArH naphthalene external), 7.03 (d, ³J = 8.8 Hz, 1H, ArH naphthalene external), 6.95–6.88 (m, 4H, ArH XB macrocycle hydroquinone), 6.88–6.81 (m, 4H, ArH XB macrocycle hydroquinone), 6.78 (d, ³J = 8.9 Hz, 1H, ArH naphthalene external), 6.69 (s, 1H, ArH naphthalene internal), 6.35 (d, ³J = 8.7 Hz, 4H, ArH HB macrocycle hydroquinone), 6.07 (d, ³J = 8.7 Hz, 4H, ArH HB macrocycle hydroquinone), 5.85–5.82 (m, 2H, –CH=CH), 4.76–4.72 (m, 2H, –CH₂), 4.64–4.60 (m, 2H, –CH₂), 4.60–4.53 (m, 2H, –CH₂), 4.50–4.47 (m, 2H, –CH₂), 4.43–4.39 (m, 2H, –CH₂), 4.35 (s, 3H, –CH₃), 4.34–4.27 (m, 2H, –CH₂), 4.20–4.16 (m, 2H, –CH₂), 4.14–4.00 (m, 12H, –CH₂), 3.81–3.62 (m, 18H, –CH₂), 3.59–3.51 (m, 4H, –CH₂), 3.51–3.42 (m, 4H, –CH₂), 2.80–2.74 (m, 2H, –CH₂). HRMS (ESI +ve) m/z: 1588.5346 ([M − Cl]⁺, C₈₃H₉₁IN₅O₁₉ requires 1588.5347).

Iodo-triazolium functionalised [2]catenane hexafluorophosphate salt (16·PF₆)

16·Cl (3.52 mg, 0.00217 mmol) was dissolved in CHCl₃ (15 mL) and washed with 0.1 M NH₄PF_6(aq) (10 × 10 mL) and water (10 mL) before being dried over MgSO₄ and filtered. The solvent was then removed in vacuo to give 16·PF₆ as an off-white solid (3.16 mg, 84%). ¹H NMR (500 MHz, CDCl₃): δ 8.47 (br s, 2H, –NH), 8.30–8.20 (m, 2H, ArH isophthalamide external), 7.71–7.60 (m, 4H, ArH naphthalene external), 7.51 (t, ³J = 7.8 Hz, 1H, ArH isophthalamide external), 7.39 (br s, 1H, ArH isophthalamide internal), 7.23 (s, 1H, ArH naphthalene internal), 7.15 (s, 1H, ArH naphthalene internal), 7.11–7.05 (m, 2H, ArH naphthalene external), 7.00–6.96 (m, 1H, ArH naphthalene external), 6.94 (s, 1H, ArH naphthalene internal), 6.90–6.80 (m, 10H, ArH XB macrocycle hydroquinone & naphthalene internal & naphthalene external), 6.44 (d, ³J = 8.9 Hz, 4H, ArH HB macrocycle hydroquinone), 6.23 (d, ³J = 8.7 Hz, 4H, ArH HB macrocycle hydroquinone), 5.85–5.81 (m, 2H, –CH=CH), 4.56–4.51 (m, 2H, –CH₂), 4.50–4.46 (m, 2H, –CH₂), 4.43–4.34 (m, 6H, –CH₂), 4.24 (s, 3H, –CH₃), 4.14–3.97 (m, 18H, –CH₂), 3.80–3.59 (m, 20H, –CH₂), 3.59–3.53 (m, 2H, –CH₂), 3.19–3.13 (m, 2H, –CH₂), 2.90–2.85 (m, 2H, –CH₂). ¹⁹F NMR (283 MHz, CDCl₃): δ –71.7 (d, J = 718.3 Hz). ³¹P NMR (122 MHz, CDCl₃): δ −144.1 (sept., J = 713.7 Hz). HRMS (ESI +ve) m/z: 1588.5346 ([M − PF₆]⁺, C₈₃H₉₁IN₅O₁₉ requires 1588.5347).

Acknowledgements

J.M.M. thanks the EPSRC for a DTA studentship and Johnson Matthey for a CASE Award. A.C. thanks the European Research Council for postdoctoral funding under the European Union's Seventh Framework Program (FP7/2007–2013) ERC Advanced Grant agreement number 267426.

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Footnote

† Electronic supplementary information (ESI) available: NMR spectra of novel compounds, titration protocols and additional fluorescence titration spectra. See DOI: 10.1039/c4ra15380d

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