Nitrosonium complexation by the tetraphosphonate cavitand 5,11,17,23-tetramethyl-6,10:12,16:18,22:24,4-tetrakis(phenylphosphonato-κ2 O,O)resorcin(4)arene

Resorcinarene-based tetraphosphonate cavitands are versatile molecular receptors which combine a π-basic aromatic cavity with hydrogen-bond acceptor groups at their upper rim. Their complexation properties span from neutral molecules to cationic species, and have been extensively studied both in solution and in the solid state. In this paper, we report the NMR solution studies and the crystal structure of a new supramolecular complex between a tetraphosphonate cavitand and the nitrosyl cation NO+. The cation is disordered over two equivalent positions, and interacts with two adjacent P=O groups at the upper rim of the cavitand through a dipole–charge interaction.


Chemical context
Cavitands (Cram, 1983;Cram & Cram, 1994) are synthetic organic compounds endowed with a rigid, pre-organized cavity that have been used extensively both in solution (Hooley & Rebek, 2009;Pochorovski et al., 2012) and in the solid state (Riboni et al., 2016) as molecular receptors for neutral molecules and cationic species (Pinalli & Dalcanale, 2013). This versatility stems from the possibility of decorating both the upper and the lower rim of the resorcinarene skeleton with desired functionalities.
In our group, we have been particularly interested in tetraphosphonate cavitands of the general formula Tiiii[R, R 1 , R 2 ] (R = lower rim substituents; R 1 = upper rim substituents; R 2 = substituents on the P atom) in which the upper rim of the macrocycle is functionalized with four P O groups, all pointing inwards towards the cavity (Pinalli & Dalcanale, 2013). In this way, the basicity of the cavity, useful for C-HÁ Á Á recognition, is enriched with dipolar groups that can act both as hydrogen-bond acceptors and interact with cationic species through cation-dipole interactions.
The nitrosonium ion and its salts have been studied in the past to investigate similarities and differences with the O 2 + ion in terms of size, ionization potential, electron affinity, oxida-tion power etc (Mazej et al., 2009). Moreover, the NO + cation can be used as a model for nitrogen oxides in molecular recognition phenomena. Indeed, the formation of stable, hostguest complexes between NO + cations and organic molecular receptors has been studied in solution with resorcinarenes (Botta et al., 2007) or with calixarenes, both in solution (Zyryanov et al., 2002(Zyryanov et al., , 2003 and in the solid state (Rathore et al., 2000). In particular, nitrosonium hexachloroantimonate was shown to form an inclusion compound with tetramethoxyand tetra-n-propoxycalix(4)arenes due to the interaction between the positive charge of the guest and the electron-rich aromatic cavity of the host (Rathore et al., 2000). Inspired by this work, we decided to carry out a combined solution and solid-state study of the complexation properties of the rigid tetraphosphonate cavitand 5,11,17,23-tetramethyl-6,10:12,16:18,22:24,4-tetrakis(phenylphosphonato-O,O 0 )resorcin(4)arene (from now on indicated as Tiiii[H, CH 3 , C 6 H 5 ]) towards NOBF 4 .

Studies in solution
Preliminary 31 P and 1 H NMR studies were performed to probe the complexation properties of the cavitand towards the nitrosonium ion in solution. To this purpose, we synthesized the cavitand Tiiii[C 3 H 7 , CH 3 , C 6 H 5 ], functionalized at the lower rim with four -C 3 H 7 alkyl chains to enhance the cavitand solubility. The NMR tube was filled with 0.5 ml of a CDCl 3 solution containing the cavitand (1 mmol concentration). The NOBF 4 titrant solution was prepared by dissolving the guest in 0.4 ml (10 mmol) of the above-mentioned cavitand solution to keep the concentration of the host constant during the titration. Portions (0.25 eq., 22.5 mL) of the titrant were added by syringe to the NMR tube. During the titration, the phosphorous singlet of the cavitand shifted slightly downfield, from 6.01 (signal for the free host) to 7.42 ppm upon addition of an excess (2.5 eq.) of the guest (see Fig. S1 in the Supporting information), indicating the presence of cation-dipole interactions between the nitrosonium ion and the phosphonate groups at the upper rim. The broadening of the signal is due to the fast exchange (at the NMR time scale) of the guest inside the cavity.
In Fig. 1, the comparison between the 1 H spectra recorded after each guest addition is reported. As can be seen, the protons of the methyl group in the apical position of the cavitand skeleton (purple dot) are shifted up-field, increasing the guest concentration; this means that the presence of the NO + cation in proximity to the cavitand upper rim creates a change in the environment, which results in an overall shielding effect. On the contrary, the signals of the protons at the lower rim, namely the aromatic hydrogens (light-blue dot), the bridging methines (green dot) and the alkyl methylenic groups (red dot), are shifted downfield. This is due to the perturbation created by the BF 4 À anion, which is likely positioned among the alkyl feet of the cavitand, as already observed for counter-anions in other crystal structures previously reported . Also in this case, broadening of the signals was observed.
Following these results, solid-state studies were carried out to obtain an insight into the type, number, strength and geometry of the weak interactions taking place in the system.

Structural commentary
The molecular structure of NO@Tiiii[H, CH 3 , C 6 H 5 ]BF 4 Á-CH 2 Cl 2 is reported in Fig. 2. The complex crystallizes in the space group P1, and the asymmetric unit comprises one cavitand, one molecule of NOBF 4 (with the cation disordered over two equivalent positions) and one disordered molecule of dichloromethane. The NO + BF 4 À ionic pair is separated, and the nitrosonium ion is located within the macrocycle, not deep inside the cavity, but lying in the mean plane passing through the four phosphonate oxygen atoms O3A, O3B, O3C and O3D (for detailed geometrical parameters, see Table 1). The nitrogen and oxygen atoms of the guest point towards the lower and the upper rims, respectively, and are held in place via cation-dipole interactions with two adjacent P O groups. It is interesting to note that the NO + ion is disordered with 50% probability over two equivalent orientations [N1O1 with occupancy of 0.503 (2) and N2O2 with occupancy of 0.497 (2)   and confirms that, for these systems, the stability of the host-guest complex is entropic in origin, since the guest can choose from two up to four energetically and geometrically equivalent interaction modes with the host. In this case, the NO + cation forms two sets of strong interactions with two adjacent P O groups, which results in a better stabilizing effect than four weaker interactions with all the phosphonate moieties of the upper rim. The BF 4 À ion is outside the cavity, forming weak C-HÁ Á ÁF interactions with the cavitands (see Section 4 for details).
The dichloromethane solvent molecule is heavily disordered and could not be modelled, but its residual electron density, occupying a void of 312 Å 3 (Spek, 2015) is located in the hydrophobic pockets among the cavitands.

Supramolecular features
In the lattice, the cavitands form a supramolecular ribbon along the a-axis direction through a series of C-HÁ Á Á interactions between the H atoms of the methyl groups at the upper rim and the phenyl rings of the phosphonato moieties. In particular, each cavitand interacts with two adjacent ones acting simultaneously as a donor to two methyl groups and as an acceptor to two aromatic rings (see Table 2 and Fig. 3; the centroids involved are Cg1 and Cg2, represented as red and green spheres, respectively). Moreover, pairs of centrosymmetric cavitands form another set of C-HÁ Á Á interactions involving the methylenic hydrogen atoms at the lower rim and the aromatic walls of the macrocycle (see Table 2 and Fig. 3, Cg3, blue centroids). The structure is further stabilized by the presence of C-HÁ Á ÁF interactions between the hydrogen atoms of the cavitands and the fluorine atoms of the tetrafluoridoborate anion. More precisely, each BF 4 À is surrounded by five cavitands (Fig. 4), with C-HÁ Á ÁF distances ranging from 2.408 (2) to 2.653 (2) Å (  (6) PL is the mean plane passing through the four phosphonate oxygen atoms, O3A, O3B, O3C and O3D.

Figure 2
Top and side views of the title compound, NO@Tiiii[H, CH 3 , C 6 H 5 ], with a partial atom-labelling scheme. Displacement ellipsoids are drawn at the 20% probability level. Only one of the two disordered NO + ions is shown.
In the side view, the hydrogen atoms and the BF 4 À counter-ion are not shown for clarity. Cation-dipole interactions are represented as blue dashed lines.

Database survey
A search in the Cambridge Structural Database (Version 5.38, update May 2017; Groom et al., 2016) for structures containing the isolated NO fragment, with no restrictions on the charge or on the type of bond connecting nitrogen and oxygen, yielded 65 species which are, of course, very different in nature. Meaningful comparisons with our complex are only possible with the series of calixarene-based, host-guest complexes already cited in the introduction, namely GOTCAT, GOTDEY, GOTGEB, GOTHAY and GOTHAY01 (Rathore et al., 2000) and with a cationic radical calixarene derivative capable of binding neutral nitric oxide (JAHFOO; Rathore et al., 2004). In particular, in GOTCAT, the NO + cation is buried deep inside the cavity, where it interacts with two distal aromatic groups of the calixarene guest. Since the calixarene is in the 1,3-alternate conformation, two sets of cofacial benzene rings are present, and the NO + ion is equally distributed between them (see Fig. 5, one pair of rings is shown in space-filling model, the other one in capped-stick mode). The electron-rich pocket formed by the co-facial pair is essential for the complexation, and the NO + ion is not bound by a single aromatic ring alone (see, for instance, GOTDEY and GOTGEB). In the case of JAHFOO, the calixarene has been oxidized to carry an overall positive charge on its core, in order to make it a good receptor for an electron rich-guest such as nitric oxide. Nevertheless, the interaction mode is similar to that observed for GOTCAT, with two disordered NO molecules buried between two distinct pairs of distal aromatic rings (Fig. 5). Also, in the title complex the guest is disordered over two equivalent positions, but its interaction with the electron-rich cavity is negligible due to the presence of the dipolar phosphonate groups which 'hold' the NO + ion at the brim of the upper rim (Fig. 5).

Synthesis and crystallization
1 H NMR spectra were obtained using a Bruker AMX-400 (400 MHz) spectrometer. All chemical shifts () were reported in ppm relative to the proton resonances resulting from incomplete deuteration of the NMR solvents. 31 P NMR spectra were obtained using a Bruker AMX-400 (162 MHz) spectrometer. All chemical shifts () were recorded in ppm relative to external 85% H 3 PO 4 at 0.00 ppm. All commercial reagents were ACS reagent grade and used as received. The cavitands Tiiii[H, CH 3 , C 6 H 5 ] and Tiiii[C 3 H 7 , CH 3 , C 6 H 5 ] were prepared following published procedures (Tonezzer et al., 2008;Menozzi et al., 2015).

Figure 5
Comparison of the interaction modes of GOTCAT, JAHFOO (side view), and of the title compound, NO@Tiiii[H, CH 3 , C 6 H 5 ] (top view), highlighting the disorder of the guest over two equivalent positions. The space-filling view is only partial for reasons of clarity.
(1 eq.) with a dichloromethane solution of NOBF 4 (1 eq.). The mixture was left to evaporate to yield colourless single crystals of the 1:1 complex that were suitable for X-ray diffraction analysis.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. The nitrosonium ion was found to be disordered over two positions, with a refined occupancy ratio of 0.503 (2):0.497 (2). The C-bound H atoms were placed in calculated positions and refined using a riding model: C-H = 0.95-0.98 Å with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms.

Special details
Experimental. The calculated molar mass, density and absorption coefficient include two disordered dichloromethane molecules per cell which do not appear in the final files because of the refinements carried out with data subjected to SQUEEZE. 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.