Pillar[n]arene–calix[m]arene hybrid macrocyclic structures

To reserve planar chirality, enhance molecular recognition, and build advanced self-assemblies, hybrid macrocyclic hosts containing rigid pillar[n]arene and flexible calix[m]arene were designed, prepared and investigated for interesting applications. This review summarizes and discusses different synthetic strategies for constructing hybrid macrocyclic structures. Pillar[n]arene dimer with rigid aromatic double bridges provided the possibility of introducing calix[m]arene cavities, where the planar chirality was reserved in the structure of pillararene. The capacity for molecular recognition was enhanced by hybrid macrocyclic cavities. Interestingly, the obtained pillar[n]arene–calix[m]arene could self-assemble into “channels” and “honeycomb” in both the solid state and solution phase as well as donate the molecular architecture as the wheel for the formation of mechanically interlocked molecules, such as rotaxane. In addition, the pillar[n]arene and calix[m]arene could also be coupled together to produce pillar[n]arene embeded 1,3-alternate and cone conformational calix[m]arene derivatives, which could catalyze the oxidative polymerization of aniline in aqueous solutions. Except for building hybrid cyclophanes by covalent bonds, weak supramolecular interactions were used to prepare pillar[n]arene–calix[m]arene analogous composites with other pillar-like pillar[n]pyridiniums and calix-like calix[m]pyrroles, exhibiting reasonable performances in enhancing molecular recognition and trapping solvent molecules.

Bing Li is a graduate student in Xi'an Jiaotong University majored in Chemical Engineering and Technology currently. She got her bachelor's degree from Zheng Zhou University in 2021. She has great research interests in the application of supramolecular hybrid materials in catalysis.
advanced hierarchical architectures, 42,43 such as metal organic frameworks, [44][45][46][47][48] as well as energy storage and batteries. 49,50 Actually, owing to the presence of similar aromatic oligomeric structures, the development of novel structures and applications of pillar[n]arene 51 has always resembled those of calix[m]arene. 52 However, because of different substitution sites on aromatic rings, pillar[n]arene and calix[m]arene 53 always exhibit different topologies and morphologies in molecular conformation and conguration, 54 as well as diverse behaviors in particular physiochemical characteristics. 55 For example, from the molecular geometry and shape perspective, the exible structures of calix[m]arene could result in an adaptable cavity for diverse guests, 56 while the rigid conformational structures of pillar[n]arene can produce unique planar chirality. 57 It is important to compare these two attractive analogues of aromatic macrocycles in terms of their structural and physiochemical behaviors. 58 Several investigation methods have been developed for this purpose; for example, computational studies 59 such as density functional theory (DFT) 60 have been employed in investigating the diverse physiochemical properties of pillar[n]arene and calix[m]arene for different performances and applications, such as host-guest complexation. 60 Furthermore, a direct comparison between these two cyclophanes in practical experiments was also carried out. 61  Scheme 3 Two synthesis routes from the starting molecule P4 with the assistance of F1 to prepare diverse oxacalix [4]arene-bridged pillar [5] arene dimers, such as PC1, PC2 and PC3, with different planar chirality.   [5]arenes possessed R p and S p rings. Solvent molecules and hydrogen atoms were omitted for clarity. 85 Scheme 4 Schematic illustration of the synthesis of diverse planar chirality-containing pillar [5]arene-based [2]rotaxanes, such as PC4, PC5, PC8 and PC9, as well as [3]rotaxanes, such as PC6, PC7 and PC10, by utilizing previous pieces, such as double-bridged pillar [5]arene derivatives, including PC1, PC2 and PC3, as well as functional reagents, including stopper-containing F2 and F3 for the formation of axle subunits. 85 functionalization of calix[m]arene with pillar[n]arene were challenging because of several organic experimental issues, such as the diverse solubilities of the two cyclophanes in reaction solutions, 79 as well as the multivalent reactive sites 80 embedded in their structures. Thus, the current rigid skeleton of pillar[n]arene was initially considered the structural basis, and heteroatoms, such as oxygen-atom on the hydroquinone moieties of pillar[n]arene, were further used as a bridge to incorporate extra aromatic subunits via meta positions, producing an additional calix-like cyclophane cavity. Such hybrid macrocycles have particular structural characteristics, e.g., "fused" hybrid macrocyclic cavities "double-bridged" 81 by aromatic rigid linkers with unique planar chirality. 82 Furthermore, it provides the opportunity to raise another supramolecular issue, i.e., the fabrication of mechanically interlocked molecules. 82 For example, 83 1,4-dimethoxypillar [4]arene [1]hydroquinone P1 (Scheme 2) was used as the previous piece to react with the "bridging group"-1,5-diuoro-2,4-dinitrobenzene F1 (Scheme 2) in the presence of triethylamine as the catalyst in THF solutions under N 2 atmosphere to produce 2,4-dinitro-5-uorophenyl difunctionalized pillar [5]arene P2 (Scheme 2) using the classic nucleophilic aromatic substitution (S N Ar) yielding 90%. Then, P2 was dissolved in DMF to promote its solubility under K 2 CO 3 condition and prepare another nitrophenyl difunctionalized pillar [5]arene P3 (Scheme 2), yielding 99%. Interestingly, the vapor diffusion method was applied to synthesize the single crystal structures of P2 and P3 using hexane, heptane and dichloromethane, revealing that tubular and honeycombed selfassemblies 84 were formed in the solid state with solvent molecules encapsulated inside these structures (Fig. 1). 83 Considering the above organic experiment of preparing signicant previous pieces of conformationally locked A1/A2 difunctionalized pillar [5]arene P2 and P3 (Scheme 2), the pillar [5]arene/calix [4]arene-containing fused hybrid macrocyclic compound-oxacalix [4]arene-bridged pillar [5]arene dimers PC1-PC3 with diverse planar chirality (Scheme 3) were further obtained using two different synthesis strategies, such as the Scheme 4 (contd.)  85 Interestingly, PC1 and PC2 were a pair of enantiomers, as conrmed by chiral high performance liquid chromatography (HPLC), and PC3 (Fig. 2) was the achiral meso compound of PC1/PC2 as revealed by 1

Coupling independent structures of pillar[n]arene and calix[m]arene
Except for expanding the current structural skeleton of pillar [n] arene to build extra calix-like cavities, two independent structures of pillar[n]arene and calix[m]arene can be coupled via classic organic reactions. For example, tetraacyl chlorides-Scheme 5 Synthesis route for producing PC11 and PC12 by coupling thiacalix [4]arene C1 and pillar [5]arene P6. 88 Scheme 6 Synthesis of PC13 using P7 and C2. 91 containing p-tert-butylthiacalix [4]arene C1 (Scheme 5) could be integrated with amino monofunctionalized pillar [5]arene derivative P6 (Scheme 5) in dichloromethane in the presence of Hünge's base under the argon atmosphere through acylation reaction, preparing pillar [5]arene-calix [4]arene hybrid macrocycles, such as 1,3-alternate conformational calixarenecontaining PC11 (Scheme 5) and cone conformational calixarene-containing PC12 (Scheme 5), yielding 58% and 65%, respectively. 88 Interestingly, the combination of pillar [5]arene and thiacalix [4]arene into a hybrid macrocyclic system not only allowed the integration of the diverse capacities of molecular recognition towards valuable guest molecules, such as aniline and aniline/p-toluenesulfonic acid, but also promoted the oxidative polymerization of aniline in aqueous p-toluenesulfonic acid solutions by increasing the yield and molecular weight of emeraldine.

Integrating pillar-like and calix-like aromatic cyclic oligomers
In addition to the direct coupling of pillar[n]arene and calix[m] arene into hybrid macrocyclic structures, other pillar-like and calix-like macrocycles, such as heteroatom-containing ones, were employed to resemble fused cyclophanes. Owing to the introduction of heteroatoms, the capacity for molecular recognition generated from fused macrocycles was enhanced.
For example, carboxylate 89,90 difunctionalized pillar [5]arene P7 (Scheme 6) was reacted with the calix-like nitrogen-rich macrocycle-calix [4]pyrrole C2 (Scheme 6) via an esterication reaction in the presence of catalytic amounts of 1-(3dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) and 4-dimethylaminopyridine (DMAP), leading to the formation of pillar [5]arene-calix [4]pyrrole PC13 (Scheme 6) with two calix [4]pyrrole subunits on both ends yielding 50%. 91 Owing to the possession of nitrogen-rich calix [4]pyrrole structures and conformational xed pillar [5]arene moieties, PC13 exhibited enhanced inclusion ability for chiral anion salts, such as chiral (R/S)-mandelate anionic guests as tetramethylammonium salts, by a series of weak supramolecular interactions, including hydrogen bonding, cation-p, p-p stacking and C-H/p interactions. The association constants (K a ) were determined in the range of 5.15 Â 10 4 to 2.25 Â 10 5 M −1 . Particularly, the introduction of heteroatoms embedded in the macrocyclic structures provided the possibility of combining pillar-like and calix-like cyclic aromatic oligomers via noncovalent interactions, i.e., the heteroatom-containing macrocycles acting as the guest molecule to be included by the other cavity via supramolecular interactions, such as electrostatic forces. For example, 92 cationic pillar[n]pyridiniums, such as the rigid square-shaped tetramer P8 and the exible roughly hexagonal hexamer P9 (Scheme 7), were encapsulated by anionic p-sulfonatocalix [4]arene C3 (Scheme 7) in the solid state and aqueous solution phase by electrostatic attractions, and anion/p + , anion/p + /anion and p/p + interactions, leading to the co-assemblies of oppositely charged hybrid macrocycles ( Fig. 4 and 5).

Overview and outlook
In conclusion, the design, preparation and application of pillar  bridged pillar[n]arene dimers further provided the pillar[n] arene cavity as the wheel to integrate with "dumb-bell"-like linear molecules, affording mechanically interlocked molecules, such as [2]/ [3]rotaxanes, with planar chirality. Additionally, classic organic synthetic methods, such as acylation reaction, were further carried out to directly combine independent units of pillar[n]arene and calix[m]arene, producing two types of pillar [5]arene-calix [4]arene hybrid macrocyles with 1,3-alternate and cone conformations, which were observed to have the capacity to catalyze the oxidative polymerization of aniline in aqueous solutions. Furthermore, pillar-like cyclophanes, such as pillar[n]pyridiniums, and calix-like cyclophanes, such as calix[m]pyrrole, were also used for the fabrication of hybrid macrocyclic systems with calixarene and pillararene, respectively, to resemble pillar[n]arene-calix[m] arene composites, where both covalent bonds and noncovalent interactions acted as the driving forces. Particularly, these analogous systems exhibited reasonable performances in enhancing molecular recognition and trapping solvent molecules in the solution and solid phases.
Numerous studies on the fabrication and application of pillararene-calixarene hybrid macrocycles are still attractive for future researchers, needing attention from related scientists in synthesis chemistry, physical chemistry and material science.
First, the efficient integration of pillar[n]arene and calix[m] arene together as well as the effective separation of enantiopure hybrid macrocycles 94 are still challenges in organic synthesis chemistry. In particular, owing to the possession of pillararene and the introduction of larger functional groups, the planar chirality of pillararene granted future applications for hybrid macrocycles but made the separation and purication of such compounds more difficult. 95 Second, other sized pillar-like and calix-like aromatic macrocycles should be employed in the fabrication of such hybrid cyclophanes to enrich the family of pillar[n]arene/calix[m]arenebased fused cyclophanes. 96 Larger cavities of fused hybrid macrocycles not only enlarge the possibilities of complexing diverse functional guest molecules, 97 but also provide signicant backbones and building blocks for constructing advanced functional structures, such as self-assemblies and mechanically interlocked molecules. 98,99 Future applications should be further explored based on functional architectures with covalent bonds, mechanical forces and supramolecular interactions. 100 Third, a computational study is highly recommended for proposing and investigating pillararene-calixarene hybrid macrocycle-based supramolecular materials, 101,102 such as the study of different behaviors of host-guest inclusions, as well as the competition and cooperation between the two hybrid macrocycles. 103

Conflicts of interest
There are no conicts to declare.