Structural characterization of the supramolecular complex between a tetraquinoxaline-based cavitand and benzonitrile

The 2:1 supramolecular complex between a tetraquinoxaline-based cavitand and benzonitrile as a guest has been studied through X-ray diffraction analysis. One of the benzonitrile molecules in engulfed inside the macrocycle.

The structural characterization is reported of the supramolecular complex between the tetraquinoxaline-based cavitand 2,8,14,20-tetrahexyl-6,10:12,16:18,22:24,4-O,O 0 -tetrakis(quinoxaline-2,3-diyl)calix[4]resorcinarene (QxCav) with benzonitrile.The complex, of general formula C 84 H 80 N 8 O 8 •2C 7 H 5 N, crystallizes in the space group P1 with two independent molecules in the asymmetric unit, displaying very similar geometrical parameters.For each complex, one of the benzonitrile molecules is engulfed inside the cavity, while the other is located among the alkyl legs at the lower rim.The host and the guests mainly interact through weak C-H� � ��, C-H� � �N and dispersion interactions.These interactions help to consolidate the formation of supramolecular chains running along the crystallographic b-axis direction.

Chemical context
Quinoxaline cavitands (QxCavs), initially reported by Cram and co-workers (Moran et al., 1982), have been extensively studied in the past years for their molecular recognition properties.These macrocycles are obtained by bridging four times a resorcinarene scaffold with 2,3-dichloroquinoxaline derivatives, affording a deep cavity capable of engulfing aromatic guests both in solution (Giannetto et al., 2018) and in the gas phase (Vincenti et al., 1993;Cle ´ment et al., 2015;Trzcin ´ski et al., 2017).The driving forces for the formation of these host-guest complexes are non-covalent C-H� � �� and �-� interactions that are established between the receptor and the included aromatic compound (Soncini et al., 1992).Another peculiar feature of these cavitands is their ability to reversibly switch between two spatially well-defined conformations.By reorganizing the four 1,4-diazanaphthalene 'flaps' from equatorial to axial positions, these cavitands can reversibly interconvert between an expanded kite (C 2v symmetry) and a contracted vase (C 4v symmetry) form (Azov et al., 2006).All intermediate conformers being energetically disfavoured, this molecular switching involves two discrete states and can be triggered in solution by different stimuli, such as pH and temperature variation (Skinner et al., 2001;Moran et al., 1991), Zn 2+ coordination (Frei et al., 2004) and redox reactions (Pochorovski & Diederich, 2014).With their ability to close and open upon external stimulation, QxCavs can be used to grab and release molecules, acting as molecular grippers (Milic & Diederich, 2019).By incorporating these gripper-like cavitands in polymers, the pH-driven conformational switch is maintained (Brighenti et al., 2018) and can be used to regenerate QxCav-based membranes for the removal of polycyclic aromatic hydrocarbons from water under relatively mild conditions (Amorini et al., 2022).By covalently embedding QxCavs in polymeric matrices, indeed, the vase-kite switching can be controlled by mechanical stimulation (Torelli et al., 2020), leading to the unprecedented observation of an auxetic behaviour in a polymer of intrinsic microporosity (PIMs; Portone et al., 2023).The extensive versatility of these cavitands arises from the accessible functionalization of both the lower rim of the resorcinarene unit and the quinoxaline bridges.The introduction of positively charged groups on the cavitand feet, for example, was found to be a powerful tool to impart water solubility to quinoxaline-like cavitands (Zhu et al., 2022), while the insertion of a carboxyl group at the upper rim enhanced the selectivity of QxCav toward nitroaromatic volatile compounds by adding additional hydrogen-bonding interactions with the NO 2 group of the guest (Bianchi et al., 2014).As a continuation of our studies towards optimal sensors for environmental applications, we have probed the recognition ability of 2,8,14,20-tetrahexyl-6,10:12,16:18,22:24,4-O,O 0 -tetrakis(quinoxaline-2,3-diyl)calix-[4]resorcinarene (QxCav) towards benzonitrile.Benzonitrile has already been used as a guest in the conformationally vaseblocked resorcinarene cavitand EtQxBox to probe its effect on the cavitand fluorescence (Aprile et al., 2018).Quenching was demonstrated through steady-state emission analysis.In this paper, we report and analyse the crystal structure of the supramolecular host-guest complex between QxCav and benzonitrile.

Structural commentary
The complex (C 84 H 80 N 8 O 8 )•2(C 7 H 5 N) crystallizes in the space group P1, with two independent molecules (indicated as A-D and E-H) in the asymmetric unit, shown in Figs. 1 and 2, respectively.One of the benzonitrile molecules is engulfed inside the cavity, while the other is located among the alkyl legs at the lower rim.The independent cavitands, both in the vase conformation, present minor differences in the cavity dimensions, in the orientation of the benzonitrile guest and of the alkyl chains at the lower rim (one of which is disordered over two positions -see the Refinement section).
Figs. 3 and 4 show two perspective views of the cavities, whose depth has been calculated as the average distance between the mean plane passing through the groups of atoms C7 at the lower rim and the atoms C19-C20 of the upper rim (see Fig. 5a).The values are of 8.070 (2) and 8.065 (3) A ˚for A-D and E-H, respectively.The mean planes passing through the quinoxaline moieties (atoms C14-C21/N1/N2) are inclined with respect to the plane passing through the O1/O2 atoms, forming angles of 77.12 (3), 84.70 (4), 81.37 (2), 84.57(2), Perspective views of the title complex A-D with the labelling scheme for the cavitand (left) and for the benzonitrile molecules (right).The ellipsoids are drawn at the 20% probability level.For clarity reasons, only one fourth of the cavitand (A) is labelled.The same scheme is applied to the rest of the macrocycle (B, C and D).

Figure 2
Perspective views of the title complex E-H with the labelling scheme for the cavitand (left) and for the benzonitrile molecules (right; the symmetry code for the guest C1U-C7U/N1U is x, y À 1, z).The ellipsoids are drawn at the 20% probability level.For clarity reasons, only one fourth of the cavitand (E) is labelled.The same scheme is applied to the rest of the macrocycle (F, G and H).Only one orientation of the disordered alkyl chain (H) is shown for clarity.
84.60 (3), 80.51 (4), 85.37 (3) and 77.33 (3) � for the Qx moieties A, B, C, D, E, F, G and H, respectively (see Fig. 5b).Distances and angles are in good agreement with similar compounds reported in the literature, see for instance the acetone clathrate KAJFAC01 (Marsh, 2004) and other supramolecular complexes discussed in the Database survey section.

Supramolecular features
Each cavitand forms similar supramolecular complexes with two benzonitrile molecules (Figs. 6 and 7).In particular, the    Main supramolecular interactions (blue dotted lines) between the host A-D and the two benzonitrile guest molecules C1R-C7R/N1R and C1S-C7S/N1S.The centroid Cg1 is shown as a cyan sphere.

Figure 7
Main supramolecular interactions (blue dotted lines) between the host E-H and the two benzonitrile guest molecules C1T-C7T/N1T and C1U-C7U/N1U.The symmetry code for the guest C1U-C7U/N1U is x, y À 1, z.The centroid Cg2 is shown as a green sphere.guests C1R-C7R/N1R and C1T-C7T/N1T are located inside the cavity of macrocycles A-D and E-H, respectively, with the atoms C1R and C1T at 0.931 (3) and 0.979 (4) A ˚from the mean plane passing through the oxygen atoms O1/O2.The aromatic guests are inclined by 85.67 (4) � (benzonitrile R) and 82.43 (3) � (benzonitrile T) with respect to the same plane.The host and the guests mainly interact through weak C-H� � �� interactions with the aromatic walls of the cavitand (Table 1).The other two benzonitrile molecules C1S-C7S/N1S and C1U-C7U/N1U are situated among the alkyl chains of macrocycle A-D and E-H, respectively, with atoms N1S and N1U at 2.595 (2) and 2.626 (3) A ˚from the mean plane passing through the atoms C7.The most relevant (albeit quite weak) contacts are of the type C-H� � �N: they involve the nitrogen atoms N1S and N1U that interact with the C-H groups of the alkyl chains and of the aromatic rings of the lower rim, or the C-H groups C1S-H2S, C1U-H1U and C6U-H6U that interact with the N atoms N1R and N1T, respectively, of the benzonitrile guests located in the cavity (Table 1 and Fig. 8).This gives rise to supramolecular chains running along the crystallographic b-axis direction.

research communications 674
Cg1 is the centroid of the ring C1D-C6D and Cg2 is the centroid of the ring C1H-C6H.BUJNUR is a fullerene clathrate, with one molecule of benzene inside the cavity and three other molecules outside it, while the fullerene molecule interacts with the aliphatic chains of the host.The benzene molecule inside the cavity is at a distance of ca 1.2 A ˚from the mean plane passing through the oxygen atoms and forms two sets of weak interactions with the N atoms of the quinoxaline walls [C� � �N distances spanning from 3.580 (4) to 3.752 (7) A ˚].

D-H�
In the case of LIMFOE, the benzodioxole enters the cavity with the aromatic ring, fitting the space formed by the four quinoxaline walls and interacting through weak C-H� � �� contacts with the scaffold of the cavitand, in a manner similar to that of the title compound [C-H� � �centroid: 2.445 (3) A ånd 160.3 (2) � ].Differently, in the structure of LIMFOE, the dioxolane ring of the guest points inside the cavity, forming two C-H� � �� interactions with the aromatic rings of the resorcinarene scaffold [C-H� � �centroid: 2.705 (4), 2.793 (2) A ˚, 165.3 (6) and 156.0 (4) � , respectively].The different behaviour is probably due to the steric hindrance caused by the aliphatic chain of 5-allyl-1,3-benzodioxole, which cannot be conveniently accommodated inside the cavity.
The guest phenyl azide (LUDJEA; Wagner et al., 2009) also enters the cavity of the macrocycle with its phenyl ring positioned between two of the quinoxaline walls.Three of the walls are slightly tilted towards the inside of the cavity to engulf the guest completely and maximize van der Waals interactions and weak C-H� � �� contacts.The fourth wall, on the contrary, points towards the outside of the cavity due to the steric hindrance caused by the azide group.
In the case of fluorobenzene (YAGVIL), as for the title compound, the stoichiometry of the supramolecular complex is 2:1; one guest is located inside the cavity, while the other one is among the alkyl chains of the lower rim.The C-F axis of the guest inside the cavity is inclined by 19.2 (2) � with respect to the normal to the mean plane passing through the oxygen atoms, with the F atom pointing toward the portal of the vase.The interactions are mainly of van der Waals type, with the presence of the usual weak C-H� � �� interactions between the guest and the aromatic ring of the host.The orientation of fluorobenzene is slightly different since the C-F axis of the guest lies on the twofold axis passing through the centre of the cavitand.

Synthesis and crystallization
The synthesis of QxCav was carried out according to the literature (Soncini et al., 1992).All commercial reagents were ACS grade and used as received.Solvents were dried and distilled using standard procedures.Prismatic, colourless single crystals of the title compound suitable for X-ray analysis were obtained by slow evaporation of a solution of QxCav in benzonitrile.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.
One of the alkyl chains in cavitand E-H (atoms C10-C13) was found to be disordered over two positions with occupancies set to 0.7 for atoms C10H-C13H and 0.3 for atoms C10I-C13I.Distances were restrained to obtain reasonable values in agreement with sp 3 hybridization.Restraints were applied to the ADP's of the atoms belonging to the disordered alkyl chain using the commands SIMU and DELU.
The highest peak (1.27 e A ˚À 3 at 0.9003 0.1896 0.0288) was found at 1.16 A ˚from the hydrogen atom H10A, bonded to the carbon atom C11A of an alkyl chain.This could be a sign of mild disorder, but attempts to model the disorder lead to unsatisfactory results.

Special details
Geometry.All esds (except the esd in the dihedral angle between two l.s.planes) are estimated using the full covariance matrix.The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry.An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s.planes.

Figure 3
Figure 3Side view of the cavities of the macrocycles A-D and E-H with partial labelling scheme.Alkyl chains and H atoms have been omitted for clarity.

Figure 4
Figure 4Top view of the cavities of the macrocycles A-D and E-H with partial labelling scheme.Alkyl chains and H atoms have been omitted for clarity.

Figure 5 (
Figure 5 (a) View of the mean plane passing through the atoms C7 (light blue) and of the distances from the atom C19A of the upper ring to this plane (blue dotted line).The average of the distances from atoms C19-C20 to the plane is reported in the text.(b) View of the mean plane passing through the atoms O1/O2 of the cavitand (red) and of the plane passing through the quinoxaline moiety A (green).The other planes passing through the moieties B, C, D, E, F, G and H have been calculated in the same way.Alkyl chains and H atoms have been omitted for clarity.

Figure 8
Figure 8Left and middle: interactions between the two different types of benzonitrile molecules (inside the cavity and inside the alkyl chains) for cavitands A-D and E-H.The symmetry code for the guest C1R-C7R/N1R is x, y À 1, z. Right: supramolecular chains running along the crystallographic b axis.

Table 2
Experimental details.