Macrocycle design, synthesis, and characterizationThe design of these H macrocycles is depicted in Fig. 1a. Initially, the benzimidazolone motif 1, 1,3-bis(chloromethyl)−1,3-dihydro-2H-benzo[d]imidazol-2-one, was readily obtained through modifications of the inexpensive and commercially available 2-hydroxybenzimidazole (Supplementary Figs. 1–4). Subsequent reactions with imidazole derivatives yielded C-shaped clefts 2 functionalized with different imidazoles. The final fragment cyclization of 2 with benzimidazolone motif 1 under refluxing in acetonitrile for 5 h provided the crude product of H (H = H1-H4) with Clˉ as counterions (Fig. 1b–e). Following crystallization in methanol, pure H was obtained with isolated yields ranging from 55% to 72% in 100 g batches. All four calix[2]azolium[2]benzimidazolones exhibited solubility exceeding 10 mM in water due to their cationic nature.The synthesized macrocycles H1-H4 were characterized by high-resolution mass spectrum (HRMS), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, and single crystal X-ray analysis (Supplementary Note 1 and Supplementary Figs. 5–17). These analyses provided strong evidence for the molecular formulae of H1-H4. The 1H NMR spectra of H1-H4 recorded in D2O revealed only one set of sharp resonances, indicative of their highly symmetrical structures. The introduction of sterically hindered benzimidazolone resulted in the suppression of azolium rings flipping45,51, leading to the conformational immobilization of H. In all four cases, the resonance corresponding to the N-CH-N proton of azolium units became invisible in the 1H NMR spectra recorded in D2O, presumably due to the exchange between active hydrogen and deuterium in D2O (H/D exchange)52,53,54. When these exchange processes occurred at a medium rate on the 1H NMR timescale, N-CH-N resonances broadened into the baseline. Notably, the 1H NMR spectra of millimolar D2O solutions of free H1-H4 exhibited sharp proton signals owing to their rigidity. Moreover, the aromatic cavities of H could be further modified by introducing substituents at their upper rims, yielding calix[2]azolium[2]benzimidazolones H5-H7 functionalized with arenes, amides, and esters chains (Supplementary Figs. 18-22).Macrocycle crystal structureH exhibits favorable crystallization properties, yielding single crystals suitable for single-crystal X-ray diffraction experiments through slow vapor diffusion of i-Pr2O into a mixture of H2O and MeOH of H at room temperature. As depicted in Fig. 1, H1-H4 are constructed from four connected N-heterocycle cores by covalent attachment of walls, resulting in one open end and one bottom plane consisting of two O and two H coordination sites. H adopts a symmetrical vase-shaped conformation with different distances between the upper and lower rims ranging from 9.92 to 11.40 Å and 3.14 to 3.38 Å (Fig. 1f–m), respectively. In addition to the two imidazolium walls, the inclusion of benzimidazolone scaffolds provides a four-wall container H1 with a deep intramolecular cavity (5.74 Å). Further substitution of benzimidazolium derivatives in each imidazolium group yields the four-wall aryl-extended macrocycles H2-H4 (5.87, 7.14, and 7.36 Å in height, respectively). The pairs of azlolium and benzimidazolone units in H1-H4 are arranged pseudo-face-to-face. Considering the plane established by the methylene bridges, two benzimidazolone units point in the same direction, resulting in torsion angles of approximately 58.1˚, 77.2˚, 76.4˚, and 76.1˚ for H1-H4 (Supplementary Fig. 24). Accordingly, the dihedral angles of two azolium units are approximately 68.4˚, 43.2˚, 39.8˚, and 40.9˚ in H1-H4, while possessing similar corner angles of about 110˚. The net result is the formation of a confined cavity with a hydrophobic upper rim and a relatively hydrophilic lower rim simultaneously. The cavities of H1-H4 are electron-deficient and hydrophobic in water, defined by two azolium and two bezimidazolone units, thereby serving as binding pockets for selectively binding electron-rich guests with high affinities. Herein, a series of aldehydes, ketones, and nitriles (G1-G29) were tested as guests (Fig. 2).Fig. 2: Chemical structures of the neutral molecules involved in this research as guest.Guest number used in other places can be found here.In the packing diagram, one benzimidazolone subunit is partially located inside the cavity of an adjacent H1, stabilized by C-H···π interactions, while arranged parallel and opposite to another adjacent H1 through π···π interactions (Supplementary Fig. 25), resembling the arrangement observed in H3 in the solid state (Supplementary Fig. 27). In contrast, H2 acts as a linker between two adjacent H2 in the pseudo-head-to-head and tail-to-tail modes, respectively, connecting the components within a two-dimensional (2D) plane to form lamellar superstructures based on multiple C-H···π and C-H···O interactions (Supplementary Fig. 26). H4 stacks in an opposite orientation directed by C-H···O and π···π interactions (Supplementary Fig. 28).Guest inclusion studiesThe complexation of the macrocycle H with butyraldehyde (G2) was investigated in the solid state. X-ray crystallography revealed the formation of G2@H host–guest complexes (Fig. 3), facilitated by their inherent characteristics of preorganized cavities and multiple non-covalent binding sites. In all complexes, each G2 molecule is situated within the cavity of H by lone pair···π and C−H···π interactions55. H1-H4 behave as electron-deficient macrocyclic hosts, accommodating aldehydes within their vase cavities composed of two azolium heterocycles and two benzimidazolone rings.Fig. 3: Different views of the single crystal structure of G2@H.a–d Top: top views of the single crystal structures of G2@H1, G2@H2, G2@H3, and G2@H4. Hydrogen atoms of H are omitted for viewing clarity. Blue dotted lines indicate lone pair···π interactions. Black dotted lines indicate C−H···π interactions. Red dotted lines indicate C−H···O interactions. Middle and bottom: side views of the single crystal structures of G2@H1, G2@H2, G2@H3, and G2@H4 (from left to right). Hydrogen atoms of H are omitted for viewing clarity. The arrows represent distances of the rims of H. P1–P4 represent the planes of N-heterocycles, and the relevant dihedral angles are illustrated.Several noteworthy structural features were observed. First, G2 forms typical lone pair−π interactions with all four N-heterocycles, evidenced by the short distances between G2 to the centroid or plane of the N-heterocycles. For example, the oxygen atom of G2 in the G2@H1 and G2@H2 complexes exhibited distances ranging from 3.11 to 3.27 Å to the centroid of azolium rings (Fig. 3a, b, top). G2@H3 complex displayed the shortest contact with imidazolium rings, with distances of 3.03 and 3.06 Å, owing to the incorporation of 5,6-dimethyl benzimidazolium units (Fig. 3c, top). In contrast, in the G2@H4 complex, the oxygen atom of G2 is located inside the cavity, resulting in longer distances to the centroid of imidazolium rings as 3.59 and 3.64 Å (Fig. 3d, top). Second, G2 interacts with two benzimidazolone rings through lone pair−π interactions in G2@H complexes. G2@H1, G2@H2, and G2@H3 exhibit comparable lone pair−π interactions in the range of 3.07 to 3.26 Å, while G2@H4 displays relatively weaker interactions at approximately 3.64 and 4.05 Å (Fig. 3a–d, top). Third, in addition to the lone pair−π interactions mentioned above, G2 is bonded inside the cavity of macrocycle H through multiple C–H···π interactions between the hydrogen atoms of G2 and the aromatic rings of H. Notably, H2 and H3 form stronger C–H···π interactions with G2 than H1 due to the presence of benzimidazolium units, evidenced by the short distances (2.89 and 2.99 Å) between alkyl C–H of G2 and aromatic rings of the host. Furthermore, the cavity size of the host in each complex, defined by the lower rim distance between two azolium rings, increased compared to that of the parent macrocycles H1-H4 (Fig. 3a–d, middle). In G2@H4, a significant decrease in the dihedral angle of two azolium rings was observed due to the additional formation of C–H···O interactions. Lastly, the lower rim distances between two benzimidazolone rings slightly decreased (Fig. 3a–d, bottom), while the dihedral angle of two benzimidazolone rings increased, with values ranging from 45.7˚ to 76.5˚.Based on the above results, we investigated the binding ability of H1 to a series of monofunctional aldehydes (Fig. 2, G1-G13). Specifically, the proton of the aldehyde group was selected to investigate the host–guest interactions in water. In the presence of H1, all proton resonances corresponding to the aldehyde groups of G1-G13 exhibited distinct upfield shifts, indicating the formation of host−guest complexes (Supplementary Figs. 31–43). Among these complexes, large upfield shifts of the proton signals belonging to the aldehyde groups were observed in the NMR spectra of G1-G5 when H1 was introduced into water: shifts of −0.82, −0.91, −1.19, −1.90, and −1.84 ppm for G1-G5, respectively, as the alkyl chain increased. This shielding effect is expected as four N-heterocycle panels surround the aldehyde within the cavity. Considering the transformation from G1-G6 to the relevant gem-diol form in water56, G7 was selected for detailed investigation to elucidate the binding mode and interactions between host and guest in water (Fig. 4a). Upon addition of H1, all proton signals of G7 shifted upfield relative to the free guest (Fig. 4c, d, ∆δ = −0.75, −0.69, −0.22, and −0.14 ppm for protons 1, 2, 3, and 4, respectively). This shift indicates that G7 was encapsulated within the cavity of H1, consistent with the results obtained from the host–guest single-crystal analysis. Additionally, the proton signals of host H1 exhibited slight upfield shifts after complexation (Fig. 4b, c). During the titration experiment, fast exchange kinetics on the 1H NMR timescale was observed, and a 1:1 binding stoichiometry of G7@H1 was inferred from Job plot analysis (Supplementary Fig. 37).Fig. 4: Host–guest complexation between H1 and G7.a Schematic presentation of the host–guest complexation between H1 and G7 and the top and side views of the single crystal structure of G7@H1. b 1H NMR spectrum (298 K, 400 MHz, D2O) of H1. c 1H NMR spectrum (298 K, 400 MHz, D2O) of H1 after adding 1.0 equiv. of guest G7. d 1H NMR spectrum (298 K, 400 MHz, D2O) of free guest G7. The concentrations of H1 and G7 were kept constant (i.e., 1.0 mM) in all the spectra.By performing isothermal titration calorimetry (ITC) experiments, the binding constant (Ka) values for aldehydes in water are determined (Supplementary Table 1 and Supplementary Figs. 49–53). Even though all these seven aliphatic aldehydes G1-G7 can fit in the cavity of H1, G3 emerges as the superior guest. Among the seven monoaldehyde guests, G3 exhibits the largest Ka (3370 ± 233 M−1), which is one order of magnitude higher than that of G4. The binding data for G1, G2, and G5 are too weak to be obtained, consistent with our previous observations of the proton shift.To elucidate the host–guest interactions at the molecular level, we crystallized the guest-loaded single crystals to explore the effect between H1 and the aldehyde guests. As depicted in Fig. 5, each guest is located within the cavity of H1 via lone pair···π and C−H···π interactions. The aldehyde groups are positioned at the bottom of the cavity through lone pair···π interactions, while the aliphatic chains extend to the upper rim in an extended conformation through multiple C−H···π interactions. Notably, a folded chain at the end of G5 is observed in G5@H1 due to the formation of a C−H···π interaction between a fixed methylene and another H1 outside the upper rim of the cavity (Supplementary Fig. 68)34. Considering the binding constants determined by ITC experiments, we confirmed that minor structural differences significantly influenced the binding affinities of H1. Compared to free H1, the upper-rim distance between two benzimidazolone rings increases in the order of 8.24 Å (G2@H1), 8.35 Å (G3@H1), and 8.41 Å (G4@H1), indicating cavity contraction due to multiple host–guest interactions (Supplementary Fig. 70). Additionally, the dihedral angle of the two rings slightly decreases from 45.7˚ (G2@H1) to 46.8˚ (G3@H1) to 47.6˚ (G4@H1). The variations in the shape and size of host H1 formed by two pairs of opposing rings substantiate the fine- and self-tunability of the cavity. Aromatic aldehydes, including benzaldehyde, cinnamyl aldehyde, and 2-furyl acrolein, can also be complex with the host H1.Fig. 5: Single crystal structures of host–guest complexes of H1 and aldehyde guests.Side views of the single crystal structure of G@H1 (G = G1–G7, G11). Red dotted lines and black dotted lines represent the lone pair···π interaction and C-H···π interaction between the host H1 and the guest.The binding affinity, however, was not limited to aldehydes: ketones and nitriles are also complexed by H1 in water. However, there was no evidence of guest recognition when equivalent amounts of alcohol, acid, and alkyne are added under the same conditions. Four-, five-, and six-membered cyclic ketones (G16-G18) formed 1:1 host–guest complexes with H1 in water, as confirmed by 1H NMR spectroscopy and single crystal X-ray analysis (Supplementary Figs. 44–48, 71). In addition to lone pair−π interactions and C-H···π interactions, C−H···N hydrogen bonding interactions also supported the complexation between nitriles and H1 within the range of 3.09–3.48 Å (Supplementary Fig. 72). A series of linear, branched chain, and even cyclic nitriles (G19-G28) could be accommodated in the cavity of H1 to form 1:1 host–guest complexes (Supplementary Figs. 54–63, 73–86).The stoichiometry of the host–guest complexes also depended on the number of polar groups and the length of aliphatic chains. While the rim atoms of H1 exhibited little self-complementarity, the ditopic guests appeared to induce the formation of a capsule, resulting in 2:1 host–guest complexes. For aldehydes, the extended capsule could be formed from H1 and glutaraldehyde or adipaldehyde guests (G14, G15) through multiple lone pair−π interactions, C-H···π interactions, and hydrophobic effects (Fig. 6a, b). Nitriles up to glutaronitrile (G25-G28) resulted in 1:1 host–guest complexes, whereas longer adiponitrile (G29) formed a 2:1 complex in which G29 was incarcerated inside the capsule in an extended conformation in water (Fig. 6c).Fig. 6: Single-crystal X-ray diffraction analysis of host–guest capsules.a–c Single-crystal X-ray molecular structures of capsule complexes between H1 and G14, G15, and G29. Green dotted lines represent distances between the upper rims of two host H1. The arrows represent the length of capsule complexes.Separation of valeraldehyde by nonporous adaptive crystals H1αValeraldehyde holds significant importance as a key feedstock chemical in the chemical industry, finding applications in fragrance production, resin chemistry, and rubber accelerators. Typically, valeraldehyde is industrially synthesized through the hydroformylation of 1-butene in the presence of a catalyst57. However, this reaction inevitably yields a mixture of isomeric products, including valeraldehyde (G3, linear), 2-methylbutanal (MB, branched), and pentanol (PA), necessitating further purification through energy-consuming and environmentally unfriendly distillation processes (Fig. 7a)58,59,60.Fig. 7: Separation of G3 by nonporous adaptive crystals H1α.a Schematic representation of hydroformylation of 1-butene. b PXRD patterns of (I) original H1α; (II) H1α after uptake of G3 liquid; (III) H1α after uptake of G3/MB mixture (1:1, v/v); (IV) H1α after uptake of G3/PA mixture (1:1, v/v); (V) H1α after uptake of G3/MB/PA mixture (1:1:1, v/v/v). c Relative contents of G3 and MB adsorbed in H1α measured by gas chromatography. d Relative contents of G3, MB, and PA adsorbed in H1α measured by gas chromatography. e Recycling performance of H1α.Preliminary results suggested that H1 exhibited selective recognition toward aldehydes, enabling the discriminating and selective separation/absorption of target valeraldehyde from a mixture with MB and PA. In this regard, we explore its potential use as an adsorptive separation material. Activated guest-free H1 crystals, named H1α, were obtained by heating at 60 ˚C under 0.1 torr for 12 h to remove CH3OH from the crystals. 1H NMR and thermogravimetric analysis (TGA) affirmed the complete removal of CH3OH (Supplementary Figs. 87, 88). Powder X-ray diffraction (PXRD) data suggested that the obtained H1α powder was crystalline and different from its CH3OH-containing crystals H1 (Supplementary Fig. 89), further confirming the crystal transformation induced by solvent removal. The 77 K N2 sorption test indicated the nonporous nature of H1α (Supplementary Fig. 90) and dense packing in its crystal state.Despite its nonporous feature, TGA and NMR data confirmed the effective adsorption capability of H1α toward G3 through a solid-liquid adsorption process, with the uptake amount of G3 calculated to be 0.8 molecule per H1α (Supplementary Note 2 and Supplementary Figs. 91, 97). It is noteworthy that the transformation from G3 to the relevant gem-diol form in water can be suppressed upon the formation of G3@H1α crystals, with no signals corresponding to the gem-diol form detected in the 1H NMR spectrum of G3@H1α crystals in D2O solution. On the other hand, PXRD studies were conducted to investigate the crystalline phase changes upon guest uptake (Fig. 7b and Supplementary Figs. 93, 95). The PXRD patterns changed after the adsorption of G3, indicating a structural transition from the guest-free H1α crystals to the G3-loaded crystalline structure. Based on the FTIR spectra, a new peak at 1665 cm−1, representing the carbonyl stretching vibration absorption peak of G3, appeared upon G3 adsorption (Supplementary Fig. 96), further validating the adsorption capability of H1α. These findings made H1α a potential sorbent material with aldehyde selectivity.The sorbent ability of H1α was further investigated by taking up G3 from mixtures of G3/MB and G3/PA (1:1, v/v), respectively. H1α selectively adsorbed G3, while the uptake of MB and PA was minimal (Supplementary Note 3 and Supplementary Figs. 98, 99). Gas chromatography (GC) data revealed high selectivity for G3 during these solid-liquid phase adsorption processes (96.5 and 99.1% in the G3/MB and G3/PA mixtures, respectively. Supplementary Figs. 100, 101). Furthermore, the purity of G3 absorbed in H1α reached 99.2% when mimicking a more realistic ratio of G3/MB (97:3, v/v) in the crude product after butene hydroformylation (Fig. 7c and Supplementary Fig. 102)57. Inspired by the above results, solid-liquid phase adsorption was conducted in a three-component mixture of G3/MB/PA (1:1:1, v/v/v). As expected, H1α demonstrated high selectivity towards G3 as determined by GC experiments (97.5%, Fig. 7d and Supplementary Fig. 103). Moreover, after the solid-liquid phase adsorption of this three-component mixture, the removal of guest from the G3-loaded crystals under reduced pressure and heating could lead to the recovery of the original guest-free H1α, which can be recycled 4 times without any material decomposition or performance loss (Fig. 7e, Supplementary Note 4, and Supplementary Figs. 104, 105). PXRD patterns of H1α after adsorption of equal volume mixtures of G3/MB, G3/PA, and G3/MB/PA all matched well with G3@H1 (Fig. 7b), confirming the excellent anti-interference capabilities of H1α in the purification of G3 molecules.Considering the close boiling points of cyclopentanone (G17) and cyclopentanol (CPOL), which are typically obtained as mixtures during industrial preparation, we further applied H1α in discriminating G17 and CPOL (Fig. 8)61. Upon solid-liquid phase adsorption, G17 could be separated from the G17 and CPOL mixture (1:1, v/v) with remarkably high purity (99.9%, Supplementary Figs. 106–110). H1α proved to be a powerful and practical adsorbent material due to its simple operation, high efficiency, and recyclability.Fig. 8: Selective separation applications of H1α.Schematic representation of the selective separation of G3 and G17 from a G3/MB/PA mixture and a G17/CPOL mixture, respectively.
