Dimeric resorcinarene salt capsules with very tight encapsulation of anions and guest molecules †

Crystallization of N -cyclohexyl ammonium resorcinarene tri ﬂ ate from methanol results in a dimeric capsule capable of trapping two tri ﬂ ate anions and two methanol molecules within a 341 ˚ A 3 cavity while with 1,4-dioxane as a guest it forms a new larger dimeric capsule with volume of 679 ˚ A 3 encapsulating four 1,4-dioxane and four water molecules, resulting in packing coe ﬃ cients of 0.75 and 0.67, respectively.

The concerted utilization of multiple weak interactions such as electrostatic forces, hydrogen bonding, cation/p, -CH/p and p/p interactions in the design of functional assemblies, is a growing area of contemporary supramolecular chemistry with potential applications in biology and materials chemistry. 1esorcinarenes are an important class of receptor compounds and/or building blocks in supramolecular chemistry. 2In their C 4v conformation, intramolecular hydrogen bonds between adjacent phenolic hydroxyl groups help maintain the bowl shape cavity suitable for guest binding. 2 These macrocyclic host compounds manifest a multitude of molecular recognition events, resulting in host-guest assemblies such as 1 : 1 inclusion complexes, 3 dimeric or hexameric capsular 4 assemblies and nano-tubular 5 structures in the presence of specic guest compounds under suitable conditions.
Anions have a major role in biological processes. 6Examples of anions or anionic compounds in biology include many enzyme substrates and cofactors. 6Anions are generally larger than their isoelectronic cations with wider solvation properties and are more sensitive to pH with a larger range of geometric/ structural modulations. 6These characteristics make the binding/recognition of anions more challenging when compared to cation binding. 6However, anion binding receptors and their applications as sensors, or their use in ions channels is widely reported. 7Anions can also be used to template the formation of ionic and metal coordination cages as well as interlocked systems. 8The propensity of anions to form hydrogen bonds and be involved in electrostatic interactions implies, incorporating these characteristics in the design of molecular receptors, could lead to very efficient anion receptors. 9 The N-alkyl ammonium resorcinarene halides, NARXs, are obtained by cleaving the corresponding tetrabenzoxazines 10 with mineral acids (usually HCl and HBr) under reuxing conditions. 11The concave cavity of the resorcinarenes is maintained in these large organic halide salts through a strong circular intramolecular hydrogen bonded cation-anion (/NR 2 H 2 + /X À /) 4 seam between the ammonium groups and the halides anions. 11These halide salts have been shown to be excellent halogen bond acceptors and manifest themselves as deep cavity cavitands 12 and halogen bonded capsules. 13We have recently investigated the binding modes with non-halide anions: picrate (aromatic planar), nitrate (trigonal planar) and triate (ellipsoidal). 14While the picrate salt was synthesized from the corresponding cleavage of the tetrabenzoxazine with picric acid, the nitrate and triate were obtained through anion exchange of the corresponding chloride salts with silver nitrate and silver triate, respectively. 14Although the non-spherical anion-based NAR's are less symmetrical, the main features such as the inherited "bowl" shape, the circular hydrogen bonded cation-anion seam, and the guest binding properties are retained.Compared to the spherical halides, the larger nonspherical anions broaden the opening of the "bowl", which enables the capture of either larger-sized or multiple guest molecules.This "opening" of the cavity allows new guest binding motifs to the resorcinarene family.Herein, we describe the synthesis and characterization of the N-cyclohexyl ammonium resorcinarene triate salt (NAROTf).
The X-ray diffraction study for the crystals of NAROTf, 4(OTf) 4 , obtained from pure methanol or methanol with 1,4-dioxane as a guest molecule, reveals two different dimeric capsules with different cavity sizes and encapsulation of either four or eight guests.
The 4(OTf) 4 , was synthesized according to modied procedures. 10,11,14In the reaction, the parent tetrabenzoxazine 3 is converted to the ammonium salt 4(OTf) 4 by reuxing in the presence of triic acid in isopropanol (Scheme 1).The 1 H NMR in DMSO-d 6 reveals the salts to be as symmetrical as the corresponding halide analogues NARXs in solution. 11However, the effect of the anions which are participating in the intramolecular hydrogen bond seam involving the -NH 2 and -OH groups of the resorcinarenes is apparent from the signal changes of the 4(OTf) 4 protons as compared to the 4(Cl) 4 /4(Br) 4 analogues (Fig. S1 †).
Recent studies have shown that 1,4-dioxane, 15 small alcohols, 11 N-alkyl and N-aryl amides 15 as well as diamides 16 with varying spacer lengths are suitable guests for the NARXs.Interactions such as -CH/p between the guests and the p-cavity of the hosts as well as hydrogen bond interactions between the guests and cation-anion seam of the hosts are mainly responsible for these host-guest complexes.Large non-spherical anions have the ability to disrupt the cation-anion seam and subsequently affect the inner cavity of the hosts. 14The 1,4-dioxane, being a particularly excellent guest for the NARXs, 15 was utilized to study the host-guest properties of 4(OTf) 4 .In CDCl 3 at 300 K, the 1 H NMR of 4(OTf) 4 shows two signals for the -NH 2 protons of the host in a 1 : 3 ratio (Fig. 1a).The -NH 2 signals of the NARXs usually appear as a single broad signal under the same conditions. 11,12This indicates that one -NH 2 group has different hydrogen bonds with the triate anion as compared to the other three -NH 2 groups, suggesting that the symmetrical cation-anion hydrogen bond seam is broken and one of the triates resides inside the cavity.Aer the addition of one equivalent of 1,4-dioxane as the guest, the two separate -NH 2 signals merge into one slightly downeld signal (Fig. 1b).The downeld shi of the -NH 2 signals is attributed to the incavity hydrogen bond formation with the 1,4-dioxane guest. 11,12he complexation induced up-eld shi of the 1,4-dioxane protons also conrms its location in the cavity of the host 4(OTf) 4 .Thus in the presence of 1,4-dioxane, the in-cavity triate is replaced by the 1,4-dioxane guest.The replaced triate then moves to the cation-anion seam making it symmetric and thus the -NH 2 protons appear as one signal (Fig. 1).
Single crystal X-ray diffraction study gave a detail picture of the solid state properties of the host with and without suitable guest(s) as well as the interactions between the large triate anion and the cationic moieties of the resorcinarene core.Fortunately, suitable single crystals of 4(OTf) 4 with and without 1,4-dioxane molecule were obtained, revealing the structural changes induced by the large triate anions and the guest molecules on the conformation of the resorcinarene salt skeleton.
Crystallization of 4(OTf) 4 from wet methanol resulted in the dimeric capsule (OTf$MeOH) 2 @(4(OTf  2A and B).One of the triate anion in the cation-anion seam moves further away from the cavity and gives space to one of the N-cyclohexyl ammonium arms which then moves inwards lling up the remaining space.This N-cyclohexyl ammonium arm appears in a gauche conformation, partially capping the cavity with the -NH 2 hydrogens pointing outwards.The two in-cavity triate anions show short F/F contacts with each other leading to a dimeric capsule with four (two OTf À and two MeOH) included guests (Fig. 2B and C).The PLATON 17 calculated volume of the cavity is 341 Å3 .The four encapsulated guests (V OTf ¼ 87.1 Å3 and V MeOH ¼ 40.7 Å3 , 2 Â 87.1 + 2 Â 40.87 ¼ 255.6 Å3 ) occupy 75% of the cavity revealing a more dense packing within the cavity than in the crystal itself. 18The fact that the host cavity can be suitable for the encapsulation of the triate anion with denite intermolecular hydrogen bonds to the hosts is particularly interesting, Scheme 1 Synthesis of 4(OTf) 4 .since it highlights the versatility of NARXs as potential receptors for anions.
Evaporation of a wet methanol solution containing 4(OTf) 4 with a small amount of 1,4-dioxane (which is known to be excellent guest for NARXs 15 ) resulted in a capsular host-guest complex (2 Â 1,4-dioxane$2 Â H 2 O) 2 @(4(OTf) 4 ) 2 .In the presence of 1,4-dioxane guest, the four triate anions in the structure are located on the cation-anion seam as in the other symmetrical NARXs 11 (Fig. 3A).The concave cavity of the resorcinarene is broadened with the opposite N/N separation of 10.466 and 10.671 Å, compared to its halide analogues.Thus the cavity is larger than normal 11 and traps two 1,4-dioxane and two water molecules.The 1,4-dioxane at the bottom of the cavity is tightly bound from its O-atoms to the host 4(OTf) 4 via one ammonium group and to one water molecule, which is hydrogen bonded to a triate anion and to another ammonium group on the other aside of each cavity.The upper 1,4-dioxane molecule is hydrogen bonded only with one of its O-atom to the water molecules, which is hydrogen bonded to the third ammonium group and a second triate anion (Fig. 3A).The weak C-H/O hydrogen bonds supplemented by intermolecular F/F contacts resulting in the dimerization of capsule halves, encapsulating a total of eight ordered molecules (Fig. 3B) in the conned cavity with a large cavity volume of 679 Å3 . 17The eight guests (V Dioxane ¼ 94.3 Å3 and V H 2 O ¼ 19.4 Å3 , 4 Â 94.3 + 4 Â 19.4 ¼ 454.8 Å3 ) occupy 67% of the interior cavity, still much more dense than the oen referred optimal packing of 55%. 18ebek et al. 18 reported exceptions to the 55 AE 0.9% rule in rare cases with a maximum of 75%, while Bruce et al. 19 observed a higher packing efficiency of 82% with deep cavity cavitands.The (2 Â 1,4-dioxane$2 Â H 2 O) 2 @(4(OTf) 4 ) 2 capsule thus represents one of the most dense dimeric capsules.

Conclusions
In summary, the NAROTf, 4(OTf) 4 , was synthesized by opening the tetrabenzoxazine ring with triic acid. 10,11,14The NMR studies in CDCl 3 and the single crystal X-ray structure from  crystals obtained from wet methanol, showed the deformation of the normally existing cation-anion seam 11 with an inclusion of one of the triate anion into the cavity.Upon addition of small amount of 1,4-dioxane to this system, the 1 H NMR in CDCl 3 proves that 1,4-dioxane will readily occupy the resorcinarene cavity thus replacing the encapsulated triate and driving it out from the cavity to re-from the normal circular cation-anion hydrogen bonded seam.In the solid state, the NAROTf forms two structurally different dimeric capsules.From wet methanol a six-component dimeric capsule (OTf$MeOH) 2 @(4(OTf) 3 MeOH) 2 encapsulating two triate anions and two methanol molecules is formed, while 1,4-dioxane being present, a 10-component dimeric capsule (2 Â 1,4-dioxane$2 Â H 2 O) 2 @(4(OTf) 4 ) 2 is formed, showing a very tight encapsulation of four 1,4-dioxane and four water molecules.Both capsules were analysed by single crystal X-ray diffraction studies.The (OTf$MeOH) 2 @(4(OTf) 3 MeOH) 2 capsule has a packing coefficient of 0.75, induced by the enhanced short F/F contacts of the two encapsulated and hydrogen bonded triate/H-OMe complexes.The fact that the resorcinarene salt cavity was found to be suitable for the encapsulation of the triate anion with denite intermolecular hydrogen bonds to the hosts is particularly interesting, since it opens the possibility of these systems to recognize anions under certain conditions.The 10-component capsule (2 Â 1,4-dioxane$2 Â H 2 O) 2 @(4(OTf) 4 ) 2 has a packing coefficient of 0.67, a very high or maybe highest number of bound (eight) neutral guest molecules inside the conned space of a dimeric capsule.Weak F/F contacts were observed in both dimeric capsules.Despite their generally weak nature, they seem to be crucial for the capsule formation.The resorcinarene salts, in short NARXs, are surprisingly versatile receptors that can recognize neutral compounds, act as halogen bond acceptors and now encapsulate anions through the combination of weak interactions.
) 3 MeOH) 2 .The symmetry of 4(OTf) 4 observed in DMSO-d 6 solution is broken in the solid state.The resorcinarene skeleton is heavily distorted and the circular (/NR 2 H 2 + /X À /) 4 hydrogen bond seam found in the corresponding 4(Cl) 4 /4(Br) 4 analogues no longer exists in this structure.Instead, the hydrogen bond seam is now constructed by the four ammonium groups, three triate anions and one MeOH molecule, the fourth triate being hydrogen bonded to a MeOH molecule and included into the cavity of 4(OTf) 3 MeOH.The location of the triate inside the cavity is also supported by the NMR analysis in solution.The bound MeOH is xed deeply in the cavity of 4(OTf) 3 MeOH by N-H/O MeOH and O-H MeOH /O hydrogen bonds just below the encapsulated tri-ate anion, interacting with the bottom of the host cavity via C-H/p interactions (Fig.

Fig. 2
Fig. 2 X-ray structure of the dimeric capsule (OTf$MeOH) 2 @(4(OTf) 3 MeOH) 2 : (A) one half of the capsule with intramolecular hydrogen bonds shown in black dotted lines.(B) The dimeric capsule with encapsulated guests in CPK mode.(C) Sliced CPK model to show the encapsulation of the guests in the dimeric capsule.The in-cavity guests are shown in gold colour.

Fig. 3
Fig. 3 X-ray structure of the dimeric capsule (2 Â 1,4-dioxane$2 Â H 2 O) 2 @(4(OTf) 4 ) 2 : (A) one half of the capsule with intramolecular hydrogen bonds shown in black dotted lines.(B) The dimeric capsule with encapsulated guests in CPK mode.(C) Sliced CPK mode to show the encapsulation of the guests in the dimeric capsule.The in-cavity guests are shown in gold colour.