Host–guest supramolecular interactions between a resorcinarene-based cavitand bearing a –COOH moiety and acetic acid

Acetic acid is a by-product of peracetic acid with acute irritant properties when present in air. The cavitand 5,11,17,23-tetramethyl-4,24:6,10:12,16:18,22-tetrakis(methylenedioxy)resorcin[4]arene functionalized at the upper rim with a carboxylic acid group, CavCOOH-in, was synthesized and crystallized with acetic acid to evaluate its molecular recognition properties towards this analyte in the solid state.

The cavitand 5,11,17,23-tetramethyl-4,24:6,10:12,16:18,22-tetrakis(methylenedioxy)resorcin [4]arene functionalized at the upper rim with a carboxylic acid group, CavCOOH-in, of chemical formula C 37 H 32 O 10 , was synthesized in order to study its supramolecular interactions with acetic acid in the solid state. Crystals suitable for X-ray diffraction analysis were obtained by slow evaporation of a dichloromethane-acetone solution of CavCOOH-in, to which glacial acetic acid had been added. The resulting compound, C 37 H 32 O 10 Á-2C 2 H 4 O 2 (1) crystallizes in the space group P1 and its asymmetric unit consists of one molecule of cavitand and two molecules of acetic acid, one of which is encapsulated inside the aromatic cavity and disordered over two positions with a refined occupancy ratio of 0.344 (4):0.656 (4). The guest interacts with the host primarily through its methyl group, which (in both orientations) forms C-HÁ Á Á interactions with the benzene rings of the cavitand. The crystal structure of 1 is dominated by O-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonding due to the presence of acetic acid and of the carboxylic group functionalizing the upper rim. Further stabilization is provided by offsetstacking interactions between the aromatic walls of adjacent cavitands [intercentroid distance = 3.573 (1) Å ].

Chemical context
Aseptic packaging utilizes hydrogen peroxide or peracetic acid for the sterilization of the packaging material and machines, enabling the introduction of beverages without additional thermal stress or added preservatives. By-products of peracetic acid are hydrogen peroxide and acetic acid. Acetic acid has acute irritant properties [The National Institute for Occupational Safety and Health NIOSH (https://www.cdc.gov/ niosh/index.htm)] and its exposure limit value has been set at 10 ppm TWA. It is therefore important to find an accurate method to measure acetic acid vapour in order to assess the environmental air quality. In the literature, only one example of the environmental monitoring of gaseous acetic acid has been reported (Yan et al., 2014). In particular, the authors presented the use of a quartz crystal microbalance (QCM) sensor on which a polyaniline film for the environmental monitoring of acetic acid was electrochemically polymerized. In the past, the QCM approach has also been used in combination with resorcinarene-based cavitands for the molecular recognition of short-chain linear alcohols (Melegari et al., 2008), and for the detection of aromatic hydrocarbons in water (Giannetto et al., 2018). Cavitands, bowl-shaped synthetic macrocycles (Cram, 1983), have been successfully ISSN 2056-9890 employed as sensors at the solid-gas interface Tudisco et al., 2016), and also as building blocks for crystal engineering . In order to endow the preorganized cavity with hydrogen-bonding acceptor and donor properties, a tetramethyleneresorcin[4]arene functionalized at the upper rim with a carboxylic acid group, CavCOOH-in, was synthesized as receptor for the recognition of acetic acid. Preliminary studies were then carried out in the solid state through X-ray diffraction methods on single crystals, to analyze the weak interactions responsible for the recognition event. In this context, we report herein and discuss the crystal and molecular structure of the title complex of CavCOOH-in with acetic acid, compound 1.

Figure 1
Top view of the molecular structure of 1, with the labelling scheme and displacement ellipsoids drawn at the 20% probability level. For clarity, only one of the two orientations for the disordered acetic acid molecule inside the cavity is shown.

Supramolecular features
While the main supramolecular contacts at play for the encapsulation of acetic acid inside the cavitand are C-HÁ Á Á interactions (Table 1), the crystal structure of 1 is dominated by hydrogen bonding. A chain which propagates along the caxis direction is formed by strong O-HÁ Á ÁO interactions involving the hydroxyl group O3D-H3D from the carboxylic acid at the methylene bridge and the bridging resorcinol oxygen atom O2B i of an adjacent cavitand ( Fig. 3 and Table 1). Pairs of chains form ribbons through the crystal, the cavitands facing one another, via supramolecular interactions involving the acetic acid guest. In particular, C1 0 /C2 0 /O1 0 /O2 0 forms a classical hydrogen-bonded inversion dimer with its symmetryrelated analogue at Àx + 2, Ày + 1, Àz + 1 (O2 0 -H2 0 Á Á ÁO1 0 ; Fig. 3 and Table 1). When the acetic acid guest is in the other orientation, namely C1/C2/O1/O2, this dimer is not formed, but the guest acts as a hydrogen-bond donor with the hydroxyl group O2-H2 towards the oxygen atom O4D ii of the carboxylic acid at the methylene bridge of an adjacent cavitand [symmetry code: (ii) Àx + 2, Ày + 1, Àz + 1; see Fig. 4 and Table 1). On the other hand, atom O1 forms two C-HÁ Á ÁO contacts, an intermolecular one with a methyl group at the upper rim of a symmetry-related cavitand [C7D--H7D1Á Á ÁO1 ii ] and an intramolecular one with a methylene bridge [C9A-H9A1Á Á ÁO1]. These sets of interactions are completed by another intermolecular C-HÁ Á ÁO hydrogen bond between methyl group C7C-H7C2 and the carboxyl oxygen atom O4D ii . Finally, the ribbons (highlighted in blue, red and yellow in Fig. 5) form offsetstacking interactions involving pairs of inversion-related (Àx + 1, Ày + 1, Àz + 1) C1A-C6A aromatic rings [ Fig. 5 right-hand-side; centroidcentroid distance = 3.573 (1) Å ; slippage = 1.338 Å ].

Database survey
A resorcinarene-based cavitand in which one of the four methylenic bridges is functionalized with a carboxylic acid is unique to the present day. An isomer of the title compound Intra-and intermolecular contacts (cyan and blue dotted lines, respectively) involving the acetic acid guest in the orientation C1/C2/ O1/O2. For clarity, only the H atoms involved in the formation of hydrogen bonds have been included [symmetry codes: (i) x, y, z + 1; (ii) Àx + 2, Ày + 1, Àz + 1].

Figure 3
A view of the supramolecular chain in the crystal structure of 1, propagating along the c-axis direction. For clarity, only the H atoms involved in the formation of hydrogen bonds have been included [symmetry codes: (i) x, y, z + 1; (ii) Àx + 2, Ày + 1, Àz + 1].
(XIDLIG) and its analogue with four -C 5 H 11 alkyl chains at the lower rim (XIDLEC) have been used to form supramolecular complexes with dimethylmethylphosphonate, DMMP, a nerve-gas simulant bearing a P O group (Daly et al., 2007). XIDLIG and XIDLEC do not only differ from each other in the lower rim substituents, but also in the orientation of the -COOH group (outward and inward, respectively) with respect to the cavity. The presence of this group is pivotal in providing the cavity with a hydrogen-bond donor towards the P O fragment of DMMP; when -COOH points inward, not only is this hydrogen bond formed, but DMMP enters the cavity with one of its methyl groups, forming C-HÁ Á Á interactions with the aromatic walls of the cavitand. In the case of the title compound 1, an acetic acid molecule enters the cavity with the methyl group but the hydrogen bond is formed with another symmetry-related molecule of acetic acid. The -COOH fragment on the methylene bridge is hence free to hydrogen bond to the resorcinol oxygen atom of an adjacent cavitand, giving rise to the supramolecular chain described in Section 3. A search in the Cambridge Structural Database (CSD, Version 5.38, update August 2018; Groom et al., 2016) for a cavitand bearing a carboxylic acid moiety at the upper rim gave six hits other than XIDLIG and XIDLEC, namely compounds ILIJOC and ILIJUI (Kobayashi et al., 2003), KAHMOV (Kobayashi et al., 2000), LOPKEG (Kobayashi et al., 1999), OSIYIA and OSIYOG (Aakerö y et al., 2016). In all these structures, the -COOH moiety is employed to build supramolecular architectures through hydrogen bonding. More precisely, in the case of ILIJOC and ILIJUI, a tetramethyleneresorcin[4]arene functionalized with four carboxylic groups on the aromatic walls of the cavity (A) has been used to form a heterodimeric capsule in a rim-to-rim fashion through the formation of four hydrogen bonds with a tetra(3-pyridyl)-cavitand. The previously cited cavitand A self-assembles into a one-dimensional chain (LOPKEG) or into dimeric capsules (KAHMOV) via hydrogen bonding with four 2-aminopyrimidine molecules. Similarly, OSIYIA and OSIYOG consist of supramolecular self-assembled polymers or capsules between tetracarboxylic acid functionalized cavitands and suitable N-heterocyclic linkers such as 4,4-bipyridine and 2-amino-5-bromo-4-chloro-6-methylpyrimidine.

Synthesis and crystallization
The synthesis of cavitand CavCOOH-in was carried out according to the procedure employed for the CavCOOH-out isomer (Daly et al., 2007). 1 H NMR spectra were obtained using a Bruker AMX-300 (300 MHz) spectrometer. Colourless crystals of the inclusion complex 1 were obtained by slow evaporation of a solution prepared by dissolving 0.005 mmol of the cavitand CavCOOH-in in 5 ml of a 1:1 dichloromethane and acetone solution, to which 1.1 mL (0.02 mmol) of glacial acetic acid were added.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The H atoms bound to C and O were placed in calculated positions and refined isotropically using the riding model with C-H ranging from 0.95 to 0.99 Å , O-H = 0.84 Å and U iso (H) set to 1.2-1.5U eq (C/O), the only exception being atom H9D, which was located in a difference-Fourier map and refined freely. A DIFX instruction was employed to avoid a short HÁ Á ÁH contact between atoms H9D and H8D1. Atoms O1 and O2 were refined using the EADP command. The acetic acid guest is disordered over two positions with a refined occupancy ratio of 0.344 (4):0.656 (4).

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.