A study of the interaction between inverted cucurbit[6]uril and symmetric viologens

The interaction between inverted cucuribit[6]uril (iQ[6]) and a series of symmetric viologens bearing aliphatic substituents, namely dicationic dialkyl-4,4′bipyridinium guests where the alkyl substituent is CH3(CH2)n (n = 1, 3 and 5) or benzyl, has been studied in aqueous solution by 1H NMR spectroscopy, electronic absorption spectroscopy, Isothermal Titration Calorimetry and mass spectrometry. The viologen bearing C6H5CH2 substituents has also been investigated. In the case of the dialkyl-derived guests, single crystal X-ray diffraction, on crystals grown in the presence of CdCl2, revealed the compositions to be 2(C36H36N24O12), 4(C14H18N2),Cd5Br9.56Cl10.442(H2O).2(H3O); 2(C36H36N24O12),C18H26N2,2(CdCl4),36H2O and 2(C36H36N24O12),2(C11H17N),2(CdCl4),20H2O for the use of n = 1, 3 or 5 respectively. Thus, in the solid state, in the case of both BV2+ (n = 3) and HV2+ (n = 5), an interaction of viologen with iQ[6] was observed and the structure adopted is an external ‘dumbbell-type’ structure. Page 1 of 17 New Journal of Chemistry N ew Jo ur na lo fC he m is tr y A cc ep te d M an us cr ip t Pu bl is he d on 0 1 Ju ne 2 01 8. D ow nl oa de d by U ni ve rs ity o f H ul l o n 01 /0 6/ 20 18 0 8: 14 :4 1. View Article Online DOI: 10.1039/C8NJ01589A Introduction Despite the attention that cucurbit[n]urils (Q[n]s) are receiving, [1] reports relating to the inverted cucurbit[n]urils (iQ[n]s) are far more scant. [2, 3] We have embarked upon a programme to investigate the host-guest/inclusion properties of iQ[n]s, and recently reported the ability of iQ[7] to include viologens, namely α,ω-alkyldiammonium guests. [3] In that study, iQ[7] was found, in aqueous solution, to partially encapsulate the viologen when R = H, CH3 or CH2CH3 forming 1:1 binary inclusion complexes. By contrast, the use of longer R groups led to 2:1 tertiary complexes with alkyl groups embedded in the iQ[7] cavity. In the same study, the presence of CdCl2 led to the formation of pseudorotaxanes for R = 4 and 7 in the solid state. We now extend our hostguest studies of inverted cucurbit[n]urils to the iQ[6] system, and report our observations on their interaction with dicationic dialkyl-4,4′-bipyridinium guests where the alkyl is CH3(CH2)n (n = 1, 3 and 5), as well as the viologen where the substituents are C6H5CH2 (see chart 1). We note that other groups have reported the interaction of Q[n]s (n = 6, 7, 8 or 14) with viologens in recent work; [4] viologens are of potential use in electrochromic displays. [5] Chart 1. iQ[6] and the viologens used in this study. Results and Discussion The binding interactions between each of the viologen guests and iQ[6] can be conveniently monitored using 1H NMR spectroscopic data recorded in 1M DCl solution, which is necessary due to the poor solubility in neutral D2O solution. Figure 1 shows the changes observed in the spectrum of EV2+ as progressively larger amounts of iQ[6] are added to the solution. There is little evidence of any of the peaks shifting which is consistent with a lack of interaction between iQ[6] and the viologen EV2+. Page 2 of 17 New Journal of Chemistry N ew Jo ur na lo fC he m is tr y A cc ep te d M an us cr ip t Pu bl is he d on 0 1 Ju ne 2 01 8. D ow nl oa de d by U ni ve rs ity o f H ul l o n 01 /0 6/ 20 18 0 8: 14 :4 1. View Article Online DOI: 10.1039/C8NJ01589A

Thus, in the solid state, in the case of both BV 2+ (n = 3) and HV 2+ (n = 5), an interaction of viologen with iQ [6] was observed and the structure adopted is an external

Introduction Introduction Introduction Introduction
Despite the attention that cucurbit[n]urils (Q[n]s) are receiving, [1] reports relating to the inverted cucurbit[n]urils (iQ[n]s) are far more scant.[2,3] We have embarked upon a programme to investigate the host-guest/inclusion properties of iQ[n]s, and recently reported the ability of iQ [7] to include viologens, namely α,ω-alkyldiammonium guests.
[3] In that study, iQ [7] was found, in aqueous solution, to partially encapsulate the viologen when R = H, CH3 or CH2CH3 forming 1:1 binary inclusion complexes.By contrast, the use of longer R groups led to 2:1 tertiary complexes with alkyl groups embedded in the iQ [7] cavity.In the same study, the presence of CdCl2 led to the formation of pseudorotaxanes for R = 4 and 7 in the solid state.We now extend our hostguest studies of inverted cucurbit[n]urils to the iQ [6] system, and report our observations on their interaction with dicationic dialkyl-4,4′-bipyridinium guests where the alkyl is CH3(CH2)n (n = 1, 3 and 5), as well as the viologen where the substituents are C6H5CH2 (see chart 1).We note that other groups have reported the interaction of Q[n]s Chart 1. iQ [6] and the viologens used in this study.

Results and Discussion
The binding interactions between each of the viologen guests and iQ [6] can be conveniently monitored using 1 H NMR spectroscopic data recorded in 1M DCl solution, which is necessary due to the poor solubility in neutral D2O solution.Figure 1 shows the changes observed in the spectrum of EV 2+ as progressively larger amounts of iQ [6] are added to the solution.There is little evidence of any of the peaks shifting which is consistent with a lack of interaction between iQ [6] and the viologen EV 2+ .
Page 2 of 17 New Journal of Chemistry   The situation observed for HV2+ (Figure S1) is reminiscent of that for BV 2+ , the only difference is that the aromatic protons exhibit a slight downfield shift.We propose these observations are again consistent with the formation of a 2:1 host-guest inclusion complex with the two iQ [6] molecules encapsulating the aliphatic chains.Interestingly, for iQ [7] with the same viologen, the shifts associated with the alkyl chains are more pronounced.[3] 1 H NMR spectroscopy was also used to monitor the binding behavior of iQ [6] with a viologen bearing C6H5CH2 substituents guest NV 2+ (Figure 3).The shifts associated with the C6H5CH2 substituents suggest this portion of the viologen is included in the iQ [6] again forming a 2:1 host-guest complex.This is further confirmed by the COSY spectrum of the mixture between iQ [6] and NV 2+ in 1M DCl (Figure S2, in the Supporting Information).

Mass spectrometry Mass spectrometry Mass spectrometry Mass spectrometry
Further evidence for the formation of the inclusion complexes of iQ [6] and guests EV 2+ , BV 2+ , HV 2+ and NV 2+ was provided by the MALDI-TOF mass spectrometry experiments.

UV spectroscopy UV spectroscopy UV spectroscopy UV spectroscopy
To further understand the binding of symmetric viologens to iQ [6], we also investigated, by UV-vis spectrometry, the interactions between iQ [6] and symmetric viologens.In Figure 5, the UV spectra shown were obtained in 0.1M HCl solutions containing a fixed concentration of viologens and variable concentrations of iQ [6].On gradually increasing the iQ [6] concentration in the viologens solution, the absorption band of the guest BV 2+ exhibits a progressively higher absorbance due to the formation of the host-guest complex 2iQ[6]@BV2+ .The absorbance vs. ratios of n(iQ [6])/n(BV 2+ ) data can be fitted to a 2:1 binding model.The alkyl moiety of the guests were encapsulated into the cavity of the iQ [6] host, generating a 2:1 host-guest inclusion complex.Similar changes in the absorption spectra of the guests HV 2+ and NV 2+ were observed as the iQ [6] concentration was increased.Thus, these the guests showed similar binding interactions with iQ [6] for which the alkyl moiety of the guests is embedded in the iQ [6] host.Nevertheless, the absorption band of the EV 2+ exhibits near invariable absorbance as the ratio of n(iQ [6])/n(EV 2+ ) is increased, which is different to the absorption spectra observed for the guests BV 2+ , HV 2+ or NV 2+ on increasing the iQ [6] concentration; these observations are consistent with the results of the NMR analysis.addition of increasing amounts (0 0.2 0.4 0.6…3.84.0 equiv.) of iQ [6] with an excitation of 262 nm.

Molecular structures Molecular structures Molecular structures Molecular structures
In the structures, it was not possible to locate hydrogen atoms attached to water.
However, the central oxygen atoms can be reliably located.In some of the structures, it is necessary to include H3O + for charge balancing.Although the structures are obtained from a chloride-rich solution there is clear evidence that bromide is present in the n = 1 case (presumably from the viol 2+ (Br − ) starting material).
The structure of iQ [6] with EV 2+ (n = 1): Single crystals of the iQ[6]-EV 2+ system suitable for X-ray diffraction were obtained by solvent evaporation of the filtrate in air over a period of about three weeks to afford rhombic colorless crystals.Following treatment with SQUEEZE, the composition of the compound was found to be 2(C36H36N24O12),4(C14H18N2), Cd5Br9.56Cl10.442(H2O).2(H3O),ie 2iQ [6]/4EV/Cd5Br9.56Cl10.442(H2O).2(H3O).Hydrogen atoms were not resolved, whilst the anions are 5× CdX4 2-where X is roughly two chloride and two bromide.This is not an inclusion complex, see Figure 6.This structure is much less well resolved than the other two (see below), perhaps as a result of the absence of an interaction between the viologen and the iQ [6].There is substantial disorder present in the position of the CdX4 2− anions.These anions lie in 1-D channels that extend parallel to the crystallographic c-axis between the organic components.The absence of significant hydrogen bonding to these anions is presumably a cause of the disorder.The iQ [6] and viologens are packed alternately in layers in the xy plane; the viologens are aligned with the b-axis.This is not an inclusion complex.The ethyl viologen molecules are located between the rims of two iQ [6]  The structure of iQ [6] with BV 2+ (n = 3): Again, crystals suitable for X-ray diffraction were obtained from the filtrate upon slow evaporation.The best estimate of the composition of the crystal is 2(C36H36N24O12), C18H26N2, 2(CdCl4), 36H2O, ie 2iQ [6]/ BV/2(CdCl4), 36H2O.Charge balancing is not obvious in this case.As shown in Figure 7, the crystal structure contains two unique iQ [6] molecules, two CdCl4 2− ions and one dibutyl viologen cation in the asymmetric unit and there is water of crystallisation that is poorly resolved.Presumably for the purposes of charge balancing some of the water is present as H3O + .Importantly, the viologen is encapsulated within two symmetry-related iQ [6]; every viologen is encapsulated and every iQ [6] is involved in this process.The dumbbells formed are packed in a C-centred array according to the space group symmetry.Between these exist large regions of space that are occupied by water.The butyl viologen resides with each of the alkyl chains located within the iQ [6] cavity of a different iQ [6] molecule.There are no classical hydrogen bonds but a raft of C−HO interactions between the viologen and the iQ [6].Bottom: the docking between the viologen and iQ [6].
The structure of iQ [6] with HV 2+ (n = 5): Single crystals of the iQ[6]@HV 2+ system suitable for X-ray diffraction were obtained by solvent evaporation of the filtrate in air over a period of about three weeks to afford colorless crystals of the solid products.HV1 was treated with SQUEEZE to pick up a little tiny bit of poorly ordered water.Best estimate of the composition of the crystal is

Experimental Section Experimental Section Experimental Section Experimental Section
All 1 H NMR spectra, including those for the titration experiments, were recorded at 20°C on a JEOL JNM-ECZ400S spectrometer.1M DCl was used as a field-frequency lock, and the observed chemical shifts are reported in parts per million (ppm).MALDI-TOF mass spectrometry was recorded on a Bruker BIFLEX III ultra-high resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer with a-cyano-4hydroxycinnamic acid as matrix.Absorption spectra of the host-guest complexes were performed with an Aglient 8453 spectrophotometer at room temperature.The host and guests were dissolved in deionized water.UV-visible spectra was obtained at a concentration of 2.00-4.00×10 - molL -1 guest and different iQ [6] concentrations for the iQ[6]@guest system.
Complex iQ [6]@BV 2+ : weigh accurately about 59 mg iQ [6](0.05mmol),55 mg CdCl2 (0.3mmol) and 173 mg BV 2+ (0.4mmol) into a 25 mL beaker and dissolve in 12mL of 3M HCl solution, The mixture was heated at 50℃ with stirring until the iQ [6] and guest dissolved completely.The solution was allowed to slowly evaporate under air at room temperature, whilst being kept in a shaded environment.Colorless and needlelike crystals were obtained in the beaker over about three weeks.
Complex iQ [6]@HV 2+ : weigh accurately about 59 mg iQ [6] (0.05mmol), 55mg CdCl2 (0.3mmol) and 195mg HV 2+ (0.4mmol) into a 25 mL of beaker and dissolve in 12mL of 3M HCl solution, The mixture was heated at 50℃ with stirring until the iQ [6] and guest dissolved completely.The solution was allowed to slowly evaporate under air at room temperature, whilst being kept in a shaded environment.Colorless and needlelike crystals were obtained in beaker in air over about three weeks.

Conclusions Conclusions Conclusions Conclusions
In summary, we have investigated the binding interactions of iQ [6] with a series of dialkyl-viologen dicationic guests using 1 H NMR spectroscopy and X-ray crystallography.
In aqueous solution, the alkyl chains of the viologens (BV 2+ and HV 2+ ) were engulfed into the cavity of the iQ [6] host, forming 2:1 ternary complexes.The viologen bearing C6H5CH2 substituents (NV 2+ ) behaves in a similar fashion.This result is consistent with the binding behavior of Q [6] and its derivatives, tetramethylcucurbit [6]uril (Me4Q [6]) and cyclohexanocucurbit [6]uril (Cy6Q [6]), with dialkyl-viologens.[7]By contrast, there was no significant interaction between iQ [6] and the viologen EV 2+ , which is different to the observations for Q [6] and its derivatives.[7,8] This is thought to be due to the smaller cavity of iQ [6] which contains a single inverted glycoluril units.The strong binding of iQ [6] to viologens is presumably due to the favorable ion-dipole interactions between the positively charged guest and the portal oxygen atoms of iQ [6] in addition to hydrophobic effects.Single crystals grown in the presence of CdCl2, revealed solid-state structures best described as external 'dumbbell' type in the case of both BV 2+ (n = 3) and HV 2+ (n = 5) with iQ [6].