Introduction

We recently found a convenient way to isolate an inverted cucurbit[6]uril (iQ[6]) from its normal cucurbit[6]uril (Q[6]) companion [1] and an inverted cucurbit[7]uril (iQ[7]) from its water soluble mixture [2] using a simple Dowex (H+) column. The significant difference in retardation factors (Rf) of iQ[6] and iQ[7] from other common Q[n]s could be attributed to the subtle differences in the outer surface electropositive properties of Q[n] and iQ[n], facilitating the facile separation of inverted iQ[6] or iQ[7] from their companion compounds. A characteristic feature of inverted cucurbit[n]urils (iQ[n]s, n = 6, 7) is the movement of the two methine hydrogen atoms of the glycoluril unit into the cavity, as first identified by Isaacs and Kim [3]. However, progress on iQ[n]s has been minimal [4, 5], possibly due to the difficulty of isolating iQ[n]s from their common Q[n] companions. Gejji and co-workers [6, 7] recently employed density functional theory to derive the electronic structure and NMR chemical shifts of iQ[n] hosts and inclusion complexes with particular cationic guests, and predicted that inverted cucurbit[n]urils could exhibit distinct selectivity towards guests with the appropriate shape and dimensions for fitting the internal cavity. Indeed, our recent work confirmed that inverted cucurbit[n]urils possess different properties from those of their normal companions [2, 8]. For example, Isothermal titration calorimetry (ITC) experiments revealed that values of TΔS were unusually negative for iQ[7]-alkaline earth cation (AE2+) interaction systems, but were positive for Q[7]–AE2+ interaction systems in neutral aqueous solution. Moreover, titration 1H NMR experiments revealed that interaction of 1,2-ethylenediamine with iQ[7] is mediated via a portal interaction [2], whereas interaction with Q[7] occurs in the cavity [8]. Similarly, iQ[6] differs in behaviour from Q[6]; coordination of iQ[6] with lanthanide cations (Ln3+) in the presence of the tetrachlorozincate anion [ZnCl4]2− as a structure-directing agent in aqueous acidic solution (3 M HCl) gave rise to different interaction products and isomorphous groups. Interactions were correlated with increasing atomic number as follows; interaction of iQ[6] with La3+ and Ce3+ immediately yielded precipitates; simple molecular bowl-like complexes were obtained with Pr3+ and Nd3+; coordination products of iQ[6] with Sm3+ and Eu3+ remained in solution; linear zigzag coordination polymers of alternating iQ[6] and lanthanide ions were obtained with Gd3+, Tb3+, Dy3+, and Ho3+; linear zigzag supramolecular chains containing alternating bowl-like and capsule-like complexes resulted from interaction with Er3+, Tm3+, Yb3+; Lu3+ produced linear zigzag supramolecular chains of Lu3+–iQ[6] pairs. In contrast, under the same conditions, Q[6] gave rise to only two groups: precipitates with La3+, Ce3+, Pr3+ and Nd3+, and linear zigzag coordination polymers with all other Ln3+ ions.

In the present work, we focus on host–guest interactions between iQ[6] and a series of α,ω-alkyldiammonium guests (H2N(CH2)xNH2, x = 2, 4, 6, 8, 10, and 12, named 1–6 respectively) (Fig. 1). The iQ[6]-based compounds are even less soluble than those in Q[6] systems in neutral aqueous solutions, therefore experiments were performed in 4 M HCl solutions. 1H NMR spectroscopy showed that iQ[6] only underwent specific interactions with guests 3 and 4. Interestingly, binding and dissociation of iQ[6] and guests was discernible in the 1H NMR spectra, suggesting a weak interaction between iQ[6] and guests 3 or 4, consistent with their association constants, which were estimated to be ~83 and ~41 L mol−1, respectively. In contrast, the Q[6] host displays a stronger interaction with all α,ω-alkyldiammonium guests [9, 10]. Crystal structures of iQ[6] with guests 1 and 3 were obtained with the assistance of polychloride transition metal anions as structure-directing agents. Similar to the Q[6] host, iQ[6] interacted with guest 1 via a portal interaction but interacted with guest 3 to form a cavity inclusion complex.

Fig. 1
figure 1

Structures of the inverted cucurbit[6]uril (iQ[6]), α,ω-alkyldiammonium guests (H3N(CH2)xNH3Cl2, x = 2, 4, 6, 8, 10, and 12 named 1–6)

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Experimental

Materials and methods

α,ω-alkyldiamanes (H2N(CH2)xNH2, x = 2, 4, 6, 8, 10, and 12) were purchased from Aldrich and used as supplied without further purification. α,ω-alkyldiammonium guests (H3N(CH2)xNH3Cl2, x = 2, 4, 6, 8, 10, and 12 named 1–6) were prepared by protonation of the corresponding amines with concentrated HCl. iQ[6] was prepared according to a literature method [3], and separated according to the method as we recently reported [1].

Preparation of compounds A and B

iQ[6] (20.0 mg, 0.02 mmol) and ZnCl2 (13.9 mg, 0.10 mmol) were dissolved in 1.0 mL of 6 M of HCl to prepare solution (V1), the guest 1 (18.9 mg, 0.14 mmol) was dissolved in deionized water to prepare solution (V2), which was then added with stirring to solution V1. X-ray quality crystals (compound A) could be obtained from the solution after a period of 10 days. iQ[6] (20.0 mg, 0.02 mmol) was dissolved in 1.0 mL 6 M of HCl to prepare solution (V3), Zn(NO3)2 (35.4 mg, 0.12 mmol) and guest 3 (19.8 mg, 0.17 mmol) were dissolved in 1.0 mL of water to prepare solution (V4), which was then added with stirring to solution V3. X-ray quality crystals (compound B) could be obtained from the solution after a period of 10 days. Crystal data and structure-refinement details for compounds A and B were given in table S1. Anal. calcd. for compound iQ[6][ZnCl4]·0.5·1·H3O·17H2O (A), C37H77N25O30ZnCl4 (%): C, 28.50; H, 4.98; N, 22.46, found: C, 28.44; H, 5.01; N, 22.51. Anal. calcd for compound {3@iQ[6]}·[ZnCl4]2−·[Zn(H3O)Cl3]−·18H2O (B), C42H92N26O31Zn2Cl7 (%): 27.47; H, 5.05; N, 19.83, found: C, 27.44; H, 5.09; N, 19.86.

X-ray crystallography

A suitable single crystal (~0.2 × 0.2 × 0.1 mm3) was embedded in paraffin oil and mounted on a Bruker SMART Apex II CCD diffractometer equipped with a graphite-monochromator Mo Kα radiation source (λ = 0.71073 Å, μ = 0.828 mm−1) that was operated in the ω-scan mode under a nitrogen stream (−50 °C). Data were corrected for Lorentz and polarization effects using the SAINT program, and semi-empirical absorption corrections based on equivalent reflections were also applied using SADABS. The structure was elucidated through direct methods and refined by the full-matrix least-squares method on F2 values using SHELXS-97 and SHELXL-97, respectively [11, 12]. All non-hydrogen atoms were refined anisotropically, and carbon-bound hydrogen atoms were introduced at calculated positions and treated as riding atoms with an isotropic displacement parameter equal to 1.2 times that of the parent atom. Most of the water molecules in A and B were omitted using the SQUEEZE option in the PLATON program (17 and 18 water molecules for compounds A and B, respectively). Analytical expressions for neutral-atom scattering factors were employed, and anomalous dispersion corrections were incorporated. Details of the crystal parameters, data collection conditions, and refinement statistics are summarized in Table S1, and crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication nos. CCDC-1422875 (A), 1422876 (B). These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336033).

Results and discussion

Interactions between the common Q[6] hosts and alkylamine and alkyldiamine hydrochloride guests have been extensively investigated since Q[6] compounds were first reported [9, 13–15], and no obvious interaction between Q[6] with α,ω-alkyldiamines (H2N(CH2)xNH2, x < 3) has been observed in 50 % formic acid [14]. We recently showed that the interaction of a symmetrical tetramethylcucurbit[6]uril (TMeQ[6]) with ethylenediammonium dichloride in D2O occurred at the portal position of TMeQ[6] [10], whereas iQ[6] incorporated the same guest in 4 M DCl/D2O solution in the present study, titration 1H NMR spectra appeared to indicate no obvious changes for either host or guest proton signals (Fig. 2, left). However, a closer inspection revealed that the methylene proton resonance of guest 1 experienced a downfield shift with increasing amounts of guest (Fig. 2, right), and a similar result was observed in iQ[6]-5 and iQ[6]-6 host–guest interaction systems (Figure S1 and S2, Supporting Information), and there was almost no change in the iQ[6]-2 system (Figure S3, Supporting Information). The titration 1H NMR spectra of all four host–guest interaction systems showed only one set of proton resonances for the guests, suggesting that (1) free and bound (portal and cavity) guest molecules have a high exchange ratio for binding and unbinding on the NMR time scale, and (2) portal interaction and cavity inclusion of the host and guest are competitive. The slightly upfield shift of the alkyl proton resonances indicates that the cavity inclusion dominates in the iQ[6]-1, iQ[6]-5 and iQ[6]-6 systems, while the free (portal) and cavity (inclusion) interactions are balanced in iQ[6]-2. This appears to be a common property of iQ[6] hosts, since the interaction of iQ[6] with p-phenylenediaminium guests gave rise to two interaction models in another of our recent studies that showed portal and cavity interactions in the crystal structure, but titration 1H NMR spectra showed that iQ[6] preferred to include the p-phenylenediaminium guest [16].

Fig. 2
figure 2

Titration 1H NMR spectra (400 MHz, 0.5 mL 4 M DCl/D2O) of 4 mg iQ[6] in the absence (a) and presence of (b ) 0.04, (c ) 0.11, (d) 0.25, (e) 1.0 equiv. of guest 1

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Figure 3 shows titration 1H NMR spectra obtained using a fixed equivalent of iQ[6] and various equivalents of 3 in 4 M DCl/D2O. Unlike the aforementioned systems, two sets of proton signals from 3 were seen to represent the binding and unbinding. Meanwhile, two sets of proton signals from iQ[6] were observed to represent binding and unbinding in the corresponding 1H NMR spectra, even when the host (Fig. 3b) or guest (Fig. 3d) was present in excess. This result suggests that the inclusion interaction of iQ[6] was not strong enough to completely bind guest 3, and the resultant iQ[6]-3 inclusion complex was of a lower stability. Three proton resonances corresponding to the binding of 3 were apparent, as were another three proton resonances corresponding to unbinding, and those corresponding to binding experienced an upfield shift of 0.25 ppm (Hα), 0.81 ppm (Hβ) and 0.84 ppm (Hγ), respectively. Proton resonances—corresponding to binding and unbinding of the iQ[6] host—were also observed, including the inverted methine proton resonance that displayed a remarkable upfield shift of 0.22 ppm, whereas the other proton resonances experienced a downfield shift by 0.10 ppm. Although the iQ[6]-3 interaction system is unusual in displaying resonances for both binding and unbinding of host and guest, indicating an unstable host–guest interaction, this provides a convenient way to estimate the association constant between iQ[6] and 3, and a the Ka was (83 L mol−1 based on data in Fig. 3d. Similar titration 1H NMR spectra were obtained for the iQ[6]-4 interaction system (Fig. S4, Supporting Information), with both binding/unbinding resonances visible for both hosts and guests. For this system, the balance of binding and unbinding between host and guest appeared to favor unbinding, and the Ka of the iQ[6]-4 complex (41 L mol−1 based on data from Fig. S4e, Supporting Information) is smaller than that of the iQ[6]-3 complex.

Fig. 3
figure 3

Titration 1H NMR spectra (400 MHz, 0.5 mL 4 mol/L DCl/D2O) of 4 mg iQ[6], in the absence of (a) and presence of (b) 0.10, (c) 0.56, (d) 1.96 equiv of 3

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Despite significant effort, diffraction-quality crystals for studying the interaction of iQ[6] with α,ω-alkyldiammonium guests in acidic or salt solutions (described above) could not be obtained. Generally, α,ω-alkyldiammonium dichloride guests are considered to behave as typical salts in aqueous solution, and etheylenediammonium is considered a typical dictation. [CdCl4]2− or [ZnCl4]2− anions are known to function as effective structure directing agents in the construction of Q[n]-metal coordination polymers [16, 17], and introduction of these into iQ[6]-α,ω-alkyldiammonium guest systems resulted in suitable crystals for iQ[6][ZnCl4]·0.5·1·H3O·17H2O (A) and {3@iQ[6]}·[ZnCl4]2−·[Zn(H3O)Cl3]−·18H2O (B). Figure 4a shows the overall assembly of iQ[6], [ZnCl4]2− anions and guest 1 observed in the structure of compound A. A ‘honeycomb’ structure built from a framework of [ZnCl4]2− anions can be observed (Fig. 4b), and closer inspection revealed that numerous [ZnCl4]2− anions (usually six) surround a iQ[6] molecule (Fig. 4c). The driving force is likely to be the electropositive outer surface of Q[n]s that attracts [ZnCl4]2− anions through ionic-dipole interactions, and we define this as the outer surface interaction [17, 18]. Similarly, the electronegative surface surrounding Q[n] (herein iQ[6]) attracts electropositive species such as metal ions and 1 molecules to form portal interaction products. Figure 4d shows an example of a portal interaction complex in which the protonated amine group (N25) interacts with portal carbonyl oxygens (O2 and O3) through hydrogen bonding and ionic-dipole interactions. The distances of N25-O2 and N25-O3 are 2.8 and 2.9 Å, respectively, and each 1 guest interacts with two iQ[6] molecules to form a ‘V’ type pair, with pairs linked by [ZnCl4]2− anions through the so-called outer surface interaction of Q[n]s. Thus, an iQ[6]-1-[ZnCl4]2− ternary supramolecular chain is formed (Fig. 4e).

Fig. 4
figure 4

Crystal structure of compound A: a overall view of the supramolecular assembly formed from iQ[6] molecules, guest 1 and [ZnCl4]2− anions; b [ZnCl4]2−-based honeycomb-like framework; c interaction between iQ[6] and [ZnCl4]2− anions; d interaction between iQ[6] and guest 1; e the iQ[6]-1-[ZnCl4]2− ternary supramolecular chain

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A similar supramolecular assembly was observed in the crystal structure of compound B (Fig. 5a) in which [ZnCl4]2− and [Zn(H2O)Cl3]− anions form a honeycomb-like framework (Fig. 5b), with iQ[6]s molecules occupying the cavities of the framework. Each iQ[6] molecule is surrounded by three [ZnCl4]2− and four [Zn(H2O)Cl3]− anions associated through outer surface interactions, water molecule (O1 W) is bound through a hydrogen bonding interaction, and [Zn(H2O)Cl3]− anions are coordinated through the portal carbonyl oxygen (O4) of iQ[6] (red dashed line, 2.818 Å). There is an additional interaction between portal carbonyl carbon C19 and the chloride (Cl7) from the [Zn(H2O)Cl3]− anion (blue dashed line, 3.448 Å in Fig. 5c). Unlike the interaction of iQ[6] with guest 1, interaction with guest 3 results in a pseudorotaxane conformation (Fig. 5d). As with most threaded linear alkyldiammonium guests, the two protonated amine groups (N25 and N26) of guest 3 interact with two opening portal carbonyl oxygens (O5, O6, and O8, O9) of the iQ[6] host through hydrogen bonding and ionic-dipole interactions, with Namine-Ocarbonyl distances in the range of 2.978–3.322 Å. Moreover, the protonated amine groups (N25) of the included guest 3 interact with carbonyl oxygens (O8) of neighbouring iQ[6] molecules through hydrogen bonding and ionic-dipole interactions, with N25-O8 distances of 3.051 Å. Thus, the combination of these iQ[6]-3-based pseudorotaxane and the outer surface interactions between iQ[6] with [ZnCl4]2− and [Zn(H2O)Cl3]− anions results in the formation of an iQ[6]-3 pseudorotaxane-based ‘pupae’ within the cells of the [ZnCl4]2− and [Zn(H2O)Cl3]−-based honeycomb (Fig.s 5a and 5e).

Fig. 5
figure 5

Crystal structure of compound B: a overall view of the supramolecular assembly formed from iQ[6], guest 3, [ZnCl4]2− and [Zn(H2O)Cl3]− anions; b honeycomb-like framework constructed of [ZnCl4]2− and [Zn(H2O)Cl3]− anions; c interaction of iQ[6] with [ZnCl4]2− and [Zn(H2O)Cl3]− anions; d interaction between iQ[6] and guest 3; e supramolecular chain constructed of iQ[6], guest 3, [ZnCl4]2− and [Zn(H2O)Cl3]− anions

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Conclusion

We present the first systematic investigation of the interaction of the iQ[6] host with α,ω-alkyldiammonium guests (1–6) in acidic (4 M HCl) aqueous solution using 1H NMR spectroscopy. The results revealed that only iQ[6]-3 and iQ[6]-4 interaction systems exhibit a lower exchange ratio for binding and unbinding on the NMR time scale. Moreover, both binding and unbinding of host and guest were discernible in the titration 1H NMR spectra, indicating an unstable host–guest interaction, and this provided a convenient way to estimate the association constant between iQ[6] and 3 or 4. The other guests showed no obvious interaction with iQ[6]. X-ray diffraction analysis revealed that guest 1 interacted with iQ[6] through a portal interaction, whereas guest 3 interacted with iQ[6] through a cavity interaction. Interestingly, titration 1H NMR spectra displayed a slight upfield shift of proton signals corresponding to guest 1, indicating that of the two different interactions present in this system, the inclusion interaction dominated. These results also suggest that different interaction types may be present in other iQ[6]-guest systems.