Crystal structure and supramolecular features of a bis-urea-functionalized pillar[5]arene

The crystal structure and supramolecular features are reported of a dimeric bis-urea-functionalized pillar[5]arene macrocycle, which functions as a receptor system to the DMF guest molecule.


Chemical context
The design of molecular receptors based on pillararenes is an active research area (Ogoshi & Yamagishi, 2013;Ogoshi et al., 2016;Fang et al., 2020).In particular, pillararene receptors bearing multiple urea-based substituents that possess polarized N-H groups are important derivatives in the field of molecular recognition and sensing because of their excellent guest-host interactions (Duan et al., 2012;Ni et al., 2014;Feng et al., 2017).The presence of strong hydrogen-bonding interaction sites in the macrocyclic rim provided by the presence of N-H groups is the prime factor for determining the efficiency of such host-guest interactions, and consequently, the extent of their molecular recognition ability.As a result, the number and relative position of the N-H groups with respect to the pillararene macrocycle is very crucial in such molecular receptors.Recently, we have reported the synthesis of ureafunctionalized anionic receptors based on di-and tetra-functionalized pillar [5]arenes (Vinodh et al., 2023).The influence of the receptor structure on the selectivity and binding ability toward different halides was investigated by 1 H NMR titrations, diffusion-order spectroscopy (DOSY) and isothermal titration calorimetry (ITC) experiments.It was observed that the non-covalent interactions between the receptors and the guest anions are affected by both the number of the urea substituents and their relative positions on the pillar[5]arene frame.In addition, the supramolecular self-assembly mediated by hydrogen-bonding interactions of urea-functionalized substituents on the pillararene frame in solution was also detected.Therefore, a detailed crystal-structure determination of bis-urea-functionalized pillararenes is very important for obtaining more insight into their molecular recognition characteristics.In the present communication we report the single-crystal X-ray structure of an inclusion complex of A1/A2-bis-urea functionalized pillar[5]arene (DUP) with a DMF molecule.The structural details, host-guest interactions and other supramolecular features of this macrocyclic system (DUP•DMF) were investigated and are discussed in detail.

Structural commentary
The bis-urea-functionalized pillar[5]arene (DUP) molecules crystallize in the monoclinic crystal system, space group P2 1 /c.In the crystal structure, one molecule of dimethylformamide (DMF) is encapsulated within the cavity of the pillararene, resulting in the formation of a host-guest supramolecular inclusion complex.As anticipated, the structure of the pillararene is a pentagonal-shaped macrocycle having benzyl urea substitution at both ends of the rim.The crystal structure also reveals that one of the urea substituents is oriented above the pillar [5]arene where its N-H groups are situated just above the cavity of the macrocycle and the other urea moiety is projected outwards from the pillar[5]arene ring, as depicted in Fig. 1.In this crystal, both urea-substituted arms of the pillar [5]arene were found to be disordered and this disorder was treated specially during data refinement by applying appropriate restraints.It can be seen that the guest DMF molecule engages in multiple intermolecular interactions with pillar[5] arene ring via N-H� � �O or C-H� � �� interactions, as given in Fig. 2 and Table 1 (� being the centroids of the pillar[5]arenebased C8-C13 and C29-C34 phenyl rings).The orientation of the substituted urea arm above the pillar[5]arene cavity clearly promoted pillar[5]arene-guest interactions by enabling a strong N-H� � �O hydrogen bond, as depicted in Fig. 2. Such a spatial orientation of the urea spacer and subsequent N-Hmediated interaction with the guest molecule suggests the ability of these urea-substituted pillar [5]arenes to facilitate selective encapsulation and provide stable host-guest systems in a variety of applications.

Figure 4
Packing pattern of DUB molecules in the crystal.Hydrogen atoms except those on the urea moieties are omitted for clarity.

Synthesis and crystallization
The synthesis and characterization of DUP have been described earlier (Al-Azemi et al., 2019;Vinodh et al., 2023).The first step is the synthesis of A1/A2-dibromoethoxy-pillar-[5]arene by the co-condensation method.The bromo-functionalized pillar [5]arene is then converted to amino derivatives by the reaction with sodium azide followed by catalytic hydrogenation.The bis-urea-functionalized pillar[5]arene DUP is finally synthesized upon its reaction with p-nitrophenyl benzylcarbamate.Colorless blocks of DUP•DMF crystals suitable for single-crystal analysis were grown by dissolving DUP (20mg) in DMF (0.5 mL) and keeping the solution in a 1 ml vial for 1 month.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3.Both urea-substituted spacers (C37-C45 and C47-C55) of the pillar[5]arene in DUP•DMF were found to be disordered and hence the refinement of the disordered fractions was done using the PART command.The final most satisfactory occupancies for the C37-C45-urea fraction are 0.55:0.45for the major and minor components.In the case of the C47-C55 urea fraction, the final occupancies are 0.52:0.48for the major and minor components.In this study, only the primary components of the disordered urea moieties were taken into account to calculate the intermolecular interactions (as given in Tables 1 and 2) as well as to generate Figs.2-4.The DFIX command was used to restrain the C O distances in the carbonyl groups of the urea fractions to 1.2 A ˚.In addition, the AFIX 66 command was applied to the C40B-C45B and C50A-C55A phenyl rings.In addition, DFIX commands were applied to the disordered atoms C40A-C45A and C50B-C55B to fix their bond lengths to 1.395 A ˚. Furthermore, DELU and SIMU commands were used in the refinement to restrain the thermal factors of the disordered C37A to C45B as well as C47A to C55B components.All the hydrogen atoms were positioned geometrically with C-H distances for methyl, methylene, aromatic groups being 0.96, 0.97 and 0.93 A ˚, respectively, and refined with U iso (H) = 1.2U eq (C).The N-H distances were restrained to be 0.86 A ẘith U iso (H) = 1.2U eq (N).

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.
Refinement.The single crystal data collection were made on Rigaku Rapid II diffractometer by Mo-Kα radiation at 150K.The data were processed by ′Crystalclear′ software package.The structures were then solved by direct methods by ′CrystalStructure′ crystallographic software package and the refinement was performed using SHELXL-2019/2.124.9 (16) H59A-C59-H59C 109.5 C36-C37A-N1A 118.9 ( 14

Figure 1
Figure 1Crystal structure of DUB•DMF with displacement ellipsoids at the 30% probability Hydrogen atoms are omitted for clarity.

Figure 2
Figure 2Intermolecular interactions between the pillar[5]arene host and the DMF guest; �2, and �5 are the centroids of the phenyl rings C8-C13 and C29-C34, respectively.Hydrogen atoms except those on urea moieties and the DMF molecule are omitted for clarity.

�2
and �5 are the centroids of the C8-C13 and C29-C34 phenyl rings, respectively.urea spacers.As depicted in Fig.3, this supramolecular dimer is formed mainly by N-H� � �O C interactions between two neighboring pillararenes.The urea N-H bonds in one arm of the pillar[5]arene are bound to the carbonyl C O group belonging to the urea arm of a second pillar[5]arene.Furthermore, the C O component of the other urea arm of this first pillararene is bound to the N-H groups of the second urea arm of the latter pillararene.Thus, supramolecular dimers are produced as a result of these complementary contacts between two pillar[5]arene urea arms.Overall, in the bis-urea-pillar[5]arene system, two urea N-H groups in each pillar[5]arene are involved in supramolecular dimer formation, and another N-H from the same pillar[5]arene is involved in supramolecular host-guest interaction with the DMF molecule, as is evident in Fig. 3.In addition to these dimeric interactions, there are a few other non-bonding interactions between adjacent pillar[5]arenes whose quantitative details are provided in Table 2.It is observed that each pillar[5]arene unit interacts with four neighboring pillar[5]arenes.The packing pattern of the DUP molecules when viewed along the b-axis direction is depicted in Fig. 4. The urea-based N-H� � �O hydrogen bonds through which the dimer formation occurred are also shown in this figure as blue dotted lines.This packing diagram shows sets of dimeric pillar[5]arenes propagated along the a-axis direction.However, the pillar[5]arenes are oriented in two different directions, which are almost perpendicular, as represented in green and pink colors.

Table 1
Intermolecular interactions(A ˚, � ) between the pillararene host and the DMF guest.

Table 2
Intermolecular interactions (A ˚,� ) engaged by DUP in the crystal network.

Table 3
Experimental details.