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. 2022 Jun 3;8(22):eabo2255. doi: 10.1126/sciadv.abo2255

Guest-induced amorphous-to-crystalline transformation enables sorting of haloalkane isomers with near-perfect selectivity

Jia-Rui Wu 1,2, Gengxin Wu 1, Dongxia Li 1, Dihua Dai 1, Ying-Wei Yang 1,*
PMCID: PMC9166396  PMID: 35658045

Abstract

The separation of haloalkane isomers with distillation-free strategies is one of the most challenging research topics in fundamental research and also gave high guiding values to practical industrial applications. Here, this contribution provides a previously unidentified solid supramolecular adsorption material based on a leggero pillararene derivative BrP[5]L, which can separate 1-/2-bromoalkane isomers with near-ideal selectivity. Activated solids of BrP[5]L with interesting amorphous and nonporous features could adsorb 1-bromopropane and 1-bromobutane from the corresponding equal volume mixtures of 1-/2-positional isomers with purities of 98.1 and 99.0%, respectively. Single-crystal structures incorporating theoretical calculation reveal that the high selectivity originates from the higher thermostability of 1-bromoalkane–loaded structures compared to its corresponding isomer-loaded structures, which could be further attributed to the perfect size/shape match between BrP[5]L and 1-bromoalkanes. Moreover, control experiments using its counterpart macrocycle of traditional pillararene demonstrate that BrP[5]L has better adsorptive selectivity, benefiting from the intrinsic free-rotation phenylene subunit on its backbone.

A macrocycle-based supramolecular-level adsorption material without any porosity and crystallinity is presented.

INTRODUCTION

With the increasing global demand for petrochemicals, the exploitation of new materials or strategies, expected to reduce the environmental impact and operation cost/complexity of industrial separation and purification, is of great significance and imperative. Among these, the energy-efficient separation of haloalkane compounds is a major industrial sustainability challenge (1–3). The use of macromolecular porous materials, such as metal-organic frameworks (4–6), zeolites (7–9), porous organic polymers (10–13), and covalent organic frameworks (14–18), in which the building blocks are linked together by covalent or coordinative bonds is considered one solution to solving this problem. Besides, molecular-level porous/nonporous materials, such as hydrogen-bonded organic frameworks (19–21), supramolecular organic frameworks (22–24), porous organic cages (25–27), and nonporous adaptive crystals (28–31), which are constructed by weak intermolecular interactions, also show promising applications in physical adsorption and energy-efficient separation processes. To date, these macromolecular- or molecular-level adsorption materials have been intensively investigated, and similar features could be summed up as “porosity and crystallinity of its initial state,” which means that their adsorption performance is closely correlated with their well-ordered porous frameworks or molecular arrangement.

Supramolecular macrocycle-based crystalline molecular adsorbents have attracted much attention from chemists over the past few years and acquired inestimable benefits from the development of novel synthetic macrocyclic host compounds with distinctive topologies and intriguing properties (32–36). With the increased understanding of host-guest chemistry, structure-function relationship, noncovalent interactions, and dynamic molecular assembly, the creative design of macrocycle-based supramolecular materials with growing complexity, functionality, and applicability could be implemented with great ease.

Pillararenes, a new generation of supramolecular hosts, have been classified as one of the most iconic macrocyclic containers among the well-established ones (e.g., crown ethers, cyclodextrins, cucurbiturils, and calixarenes) (37–39) and gained tremendous momentum during the modern supramolecular chemistry boom. Recently, we have presented an example of pillar[5]arene-derived macrocyclic receptor, named permethylated leggero pillar[5]arene (MeP[5]L) (40), in which two methoxy functionalities on a single one of the subunits of traditional permethylated pillar[5]arene were selectively removed. We also found that the amorphous powder of MeP[5]L can physically adsorb certain types of guest vapors accompanied by the molecular packing transition from the initially chaotic state to various ordered states. Inspired by this, we speculate that the macrocycle-based molecular materials constructed from disordered molecular building blocks without any porosity and crystallinity could also be excellent potentially applied in molecular separation.

In this work, we report the whole family of leggero pillar[n]arenes (P[n]Ls for short) and use the amorphous nonporous powders of perbromoethylated leggero pillar[5]arene (BrP[5]L) to achieve a super-efficient adsorptive separation of 1-/2-bromoalkane isomers (Fig. 1, A and B). We find that BrP[5]L can separate 1-bromopropane (1-BPR) from 2-BPR with 98.1% purity (Fig. 1C) and separate 1-bromobutane (1-BBU) from 2-BBU with 99.0% purity (50:50, v/v) (Fig. 1D), which is superior to the counterpart in traditional pillararenes, perbromoethylated pillar[5]arene (BrP[5]A). The precisely sorting capability can be ascribed to the superior cavity adaptability and tunability, benefiting from its inherent free-rotation phenylene subunit. Powder x-ray diffraction (PXRD) reveals that this adsorptive separation process is also a bottom-up molecular assembly approach from the initial guest-free amorphous to the last guest-loaded crystalline structures driven by weak intermolecular interactions in the solid state. Moreover, removing 1-bromoalkanes from 1-bromoalkanes–loaded BrP[5]L structures leads to the original guest-free amorphous state, making BrP[5]L highly recyclable without losing any performance.

Fig. 1. A general strategy for separating 1-/2-bromoalkane isomers via guest-induced restructuring of amorphous macrocyclic hosts.

Fig. 1.

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Chemical structures of (A) perbromoethylated leggero pillar[5]arene (BrP[5]L) and (B) 1-bromopropane (1-BPR), 2-BPR, 1-bromobutane (1-BBU), and 2-BBU. The size of the cavity in BrP[5]L was calculated to be 4.7 Å. The effective sizes of 1-BPR, 1-BBU, 2-BPR, and 2-BBU were calculated as 4.8, 4.8, 6.6, and 6.9 Å, respectively. Schematic representation of the separation process and mechanism of (C) 1-BPR from 1-BPR/2-BPR isomer mixture and (D) 1-BBU from 1-BBU/2-BBU isomer mixture using BrP[5]Lβ.

RESULTS

Synthesis and characterization of P[n]Ls

Selective removal of two hydroxy or alkoxy groups on one subunit of traditional P[n]As turns out to be much more unachievable because of the extreme difficulty to precisely crack two aryl-O bonds on one alkoxybenzene subunit. Previously, we discovered that the critical step for MeP[5]L synthesis is the initial construction of two kinds of coupling precursors (40). Accordingly, in this research, we successfully synthesized per-hydroxylated P[5]L (P[5]L), perethylated P[5]L (EtP[5]L), perethylated P[6]L (EtP[6]L), BrP[5]L, and two other important functional derivatives P[5]L-1 and P[5]L-2. Specifically, macrocyclization of EtP[5]L and EtP[6]L could be implemented by fragment coupling of two kinds of easily synthesized precursors (1 and 2 or 1 and 3) with paraformaldehyde in CHCl2 or CHCl3 in the presence of a catalytic amount of Lewis acid BF3·O(Et)2 at room temperature (Fig. 2A and figs. S1 to S4), resulting in EtP[5]L and EtP[6]L in isolated yields of 19 and 9%, respectively (see the Supplementary Materials). Whereafter, P[5]L could be qualitatively obtained by the O-dealkylation of EtP[5]L with an excess amount of BBr3 (fig. S5), indisputably confirming the postmodification capability of P[n]Ls.

Fig. 2. Synthesis and structures.

Fig. 2.

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(A) Synthetic route to P[n]Ls, that is, P[5]L, EtP[5]L, EtP[6]L, and functional P[5]L derivatives P[5]L-1, P[5]L-2, and BrP[5]L. (B) Energy-minimized structures and electrostatic potential surfaces of P[5]L, EtP[5]L, EtP[6]L, and BrP[5]L showing the π-electron–rich character of the aromatic cavity and the noncylindrical molecular conformation of the P[5]Ls scaffold.

The synthesis of BrP[5]L, bearing eight bromoethyl moieties, was accomplished by a facile three-step synthetic approach from P[5]L (Fig. 2A and fig. S6). First, macrocyclic intermediate P[5]L-1, i.e., ethoxycarbonyl-substituted P[5]L, can be prepared in a yield of 47% by reacting P[5]L with excess ethyl bromoacetate via a nucleophilic substitution reaction. Whereafter, the reduction of P[5]L-1 with LiAlH4 afforded the octanol P[5]L-2 in 45% yield, followed by further bromination by CBr4 and PPh3 to give the target compound BrP[5]L in 50% yield. The whole synthetic approach of these derivatives is highly convenient, efficient, and smooth, indicating the versatility and universality of P[n]L macrocycles.

P[5]L, EtP[5]L, EtP[6]L, and BrP[5]L were fully characterized by 1H/13C nuclear magnetic resonance (NMR) spectroscopies, matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) spectroscopy, and density functional theory (DFT) analysis (Fig. 2B and figs. S7 to S30). The guest-binding capability, derived from the strengths and weaknesses of intermolecular interactions, more or less relies on the in-cavity electrical properties in supramolecular macrocyclic receptors. Similar to traditional pillararenes, the electrostatic potential maps of P[n]Ls also exhibit π-electron–rich aromatic cavities with negative potential, confirming that the selective removal of functionalities on a single one phenylene subunit of traditional pillararenes has no noticeable impact on its in-cavity binding performance in the viewpoint of electrical characters. All energy-minimized structures of P[5]L, EtP[5]L, EtP[6]L, and BrP5L render a noncylindrical Ci molecular conformation with the unsubstituted phenylene subunit tilt to the inner cavity in varying degrees (Fig. 2B), which is in sharp contrast to the traditional pillar-shaped pillar[5]arenes with D5h symmetry.

Although one unsubstituted phenylene exists among the ring-forming subunits, P[n]Ls still show large enough and effective cavities for binding with different species in the solid-state (super)structure. As in Fig. 3 and figs. S31 to S36, by the stabilization of multiple intermolecular interactions, P[5]L, MeP[5]L, EtP[5]L, and BrP[5]L can encapsulate acetone, n-hexane (n-Hex), dichloromethane (DCM), or CH3CN molecule in the cavity or lattice voids to form acetone⊂P[5]L, n-Hex⊂MeP[5]L, DCM⊂MeP[5]L, CH3CN⊂MeP[5]L, CH3CN⊂EtP[5]L, and 2(CH3CN)⊂BrP[5]L, respectively. Furthermore, the structural flexibility and adaptability of P[5]Ls were proven unambiguously by x-ray crystallography. Concretely, MeP[5]L in n-Hex⊂MeP[5]L adopts an almost pillar-shaped structure, and the unsubstituted phenylene subunit has a dihedral angle (DA) of 89.9° with the pentagonal plane formed by its five methylene carbon atoms (Fig. 3B). MeP[5]L exhibited a distinct conformational change in DCM⊂MeP[5]L and CH3CN⊂MeP[5]L, where the relative DA values are 58.0° and 61.2° (Fig. 3, C and D), respectively, rendering an approximate 30° angle change in comparison with MeP[5]L in n-Hex⊂MeP[5]L. Besides, the relative DA values of EtP[6]L and BrP5L in CH3CN⊂EtP[5]L and 2(CH3CN)⊂BrP[5]L are 75.3° and 50.9° (Fig. 3, E and F), respectively, displaying obvious distinctions between each other and also varying from MeP[5]L in CH3CN⊂MeP[5]L as aforementioned, which suggest that the conformational diversity of P[5]Ls was affected by not only the guest species but also the substituent groups. All the above results reflect the remarkable adaptability and tunability of the binding cavity in P[5]L macrocycles, benefiting from the free-rotation phenylene subunit.

Fig. 3. Solid-state (super)structure of P[5]Ls.

Fig. 3.

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X-ray single-crystal structures of (A) P[5]L, (B) n-Hex⊂MeP[5]L, (C) DCM⊂MeP[5]L, (D) CH3CN⊂MeP[5]L, (E) CH3CN⊂EtP[5]L, and (F) 2(CH3CN)⊂BrP[5]L showing the structural adaptability and tunability of the binding cavity in P[5]Ls macrocycles that are benefiting from the free-rotation phenylene subunit.

Preparation and characterization of activated BrP[5]L

For adsorptive separation, guest-free– and thermodynamically favored crystalline structure of BrP[5]L (BrP[5]Lα) was obtained from recrystallization in the mixture of 2-bromobutane and methylcyclohexane (fig. S37). The resulting crystals were then subjected to vacuum at elevated temperature (110°C) for 6 hours to obtain activated adsorptive separation materials. Thermogravimetric analysis (TGA) proved that the activated powder was fully desolvated (figs. S38 and S39). PXRD demonstrated that the solids transformed from crystalline BrP[5]Lα to amorphous state (BrP[5]Lβ) upon heating (Fig. 4A and fig. S40), which could be ascribed to the relatively low melting point (138°C) of BrP[5]L, as proved by differential scanning calorimetry (DSC) experiment (fig. S41). The Brunauer-Emmett-Teller surface area of BrP[5]Lβ was determined to be 3.83 m2/g by the 77-K N2 sorption test (fig. S42), indicating its nonporous feature.

Fig. 4. Single-component bromoalkane isomer adsorption experiments.

Fig. 4.

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(A) Schematic representation of the phase transition from the initial guest-free crystalline state (BrP[5]Lα) to the guest-free amorphous state (BrP[5]Lβ) upon heating. (B and C) Time-dependent BrP[5]Lβ solid-vapor sorption plots for single-component (B) bromopropane isomer vapor and (C) bromobutane isomer vapor. (D) PXRD patterns of BrP[5]L: (I) original BrP[5]Lβ, after adsorption of (II) 2-BPR vapor, and (III) 1-BPR vapor. (E) PXRD patterns of BrP[5]L: (I) original BrP[5]Lβ, after adsorption of (II) 2-BBU vapor, and (III) 1-BBU vapor.

Single-component bromoalkane isomer adsorption experiments

Despite its nonporous nature, the adsorption property of BrP[5]Lβ toward 1-bromoalkane and 2-bromoalkane was first investigated through time-dependent single-component solid-vapor sorption experiments. As shown in Fig. 4 (B and C), 1-BPR, 2-BPR, 1-BBU, and 2-BBU can all be adsorbed by BrP[5]Lβ, and the adsorption rates of 1-BPR and 2-BPR were slightly faster than 1-BBU and 2-BBU, which took only about 1 to 2 hours to reach the saturation points upon adsorption. 1H NMR spectra and TGA results further verified the adsorption and storage capability of BrP[5]Lβ. The uptake amounts of 1-BPR, 2-BPR, 1-BBU, and 2-BBU can be calculated as ca. 1.0, 2.0, 1.0, and 1.5 mol/mol BrP[5]L at equilibrium, respectively (figs. S43 to S50).

PXRD experiments were implemented to study the structural changes of BrP[5]Lβ upon uptake of bromoalkane vapors. As shown in Fig. 4 (D and E), BrP[5]Lβ in amorphous state exhibited sharp peaks after adsorption of 1-BPR, 2-BPR, 1-BBU, and 2-BBU, which indicated that these guest-free disordered hosts transformed into new guest-loaded structures and gained crystallinity to some extent via guest-induced intermolecular interactions. Moreover, the BrP[5]L patterns after adsorption of 1-BPR or 2-BPR were different from each other, suggesting the formation of two new BrP[5]L structures. Similar results were also observed after uptake of 1-BBU and 2-BBU.

Structural analysis of BrP[5]L with bromoalkane isomers

To reveal these new guest-containing structures, we obtained single crystals of BrP[5]L loaded with 1-BPR, 1-BBU, and 2-BPR (Fig. 5). By the stabilization of multiple C─H···π (interact site distances of 2.521, 2.648, 2.775, and 3.004 Å), C─H···O (3.330 and 3.348 Å), and C─H···Br (3.394 Å) interactions (fig. S51), BrP[5]L can encapsulate one 1-BPR to form 1-BPR⊂BrP[5]L complex (space group C2, monoclinic) in the crystalline state. The pentagonal BrP[5]L molecules assemble in a herringbone packing mode. Thus, no atomic-scale channel could be found in the structure because of the two adjacent BrP[5]L molecules being staggered from each other (Fig. 5A). Moreover, the PXRD pattern of BrP[5]L after uptake of 1-BPR matched well with the simulated pattern (fig. S52), suggesting that the adsorption of 1-BPR led to the structural transition from disordered BrP[5]Lβ to 1-BPR⊂BrP[5]L. As for 1-BBU–loaded BrP[5]L structure (1-BBU⊂BrP[5]L), BrP[5]L molecules were crystallized in the space group P-1 (triclinic), and a 1:1 host-guest complex stabilized by C─H···π (interact site distances of 2.761, 2.838, 2.791, and 3.011 Å), C─H···O (2.979 and 3.374 Å), and C─H···Br (3.348 and 3.379 Å) interactions was also observed (fig. S53). BrP[5]L forms regularly window-to-window packing mode, resulting in infinite honeycomb-like one-dimensional (1D) channels with 1-BBU threaded through (Fig. 5B). Note that there are still a small quantity of disordered 1-BBU molecules located outside the cavity and links neighboring BrP[5]L through weak van der Waals contacts in 1-BBU⊂BrP[5]L (fig. S54). Despite many attempts, the PXRD pattern of BrP[5]L after taking up 1-BBU gave a poor quality of match with the corresponding simulated pattern from 1-BBU⊂BrP[5]L (fig. S55), presumably due to the lack of disordered 1-BBU molecules in the lattice voids as the crystal structure presented to us. Subsequently, DSC experiments were carried out to study the desorption behaviors of 1-BPR⊂BrP[5]L and 1-BBU⊂BrP[5]L. Contrary to the relatively normal boiling points of 1-BPR and 1-BBU (boiling point of 1-BPR: 71°C and boiling point of 1-BBU: 101°C), 1-BPR⊂BrP[5]L and 1-BBU⊂BrP[5]L began to release 1-BPR and 1-BBU molecules at ca. 125° and 105°C (figs. S56 and S57), which indicated that the thermostability of herringbone packing mode without specific channels in 1-BPR⊂BrP[5]L is higher than the honeycomb-like packing mode in 1-BBU⊂BrP[5]L, and more heat is needed to desorb the guest species.

Fig. 5. Structural analysis of BrP[5]L with bromoalkane isomers.

Fig. 5.

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Solid-state superstructures and intermolecular binding isosurfaces (visual study of weak intermolecular interaction) of (A) 1-BPR⊂BrP[5]L, (B) 1-BBU⊂BrP[5]L, and (C) 2-BPR⊂BrP[5]L.

In terms of 2-bromoalkane–loaded structures, single crystals of BrP[5]L loaded with 2-BPR (2-BPR⊂BrP[5]L) were also obtained by slow evaporation of a 2-BPR solution of BrP[5]L. Despite numerous attempts, no suitable crystal structure of 2-BBU–loaded BrP[5]L (2-BBU⊂BrP[5]L) was obtained, which could be ascribed to the molecular chirality of 2-BBU and the size mismatch between 2-BBU and the cavity of BrP[5]L. In 2(2-BPR)⊂BrP[5]L, BrP[5]L hosts were crystallized in the space group P-1 (triclinic) and formed a 1:2 host-guest assembly with 2-BPR (Fig. 5C). Driven by the stabilization of C─H···π (interact site distances of 2.880, 2.835, and 3.190 Å), C─H···O (2.786, 2.928, and 3.076 Å), and C─H···Br (distance of 3.183 Å) interactions, two 2-BPR molecules irregularly reside in the cavity rims of BrP[5]L, and the protruded Br atoms further interact with the neighboring BrP[5]L through C─H···Br (distance of 3.031 Å) interaction (fig. S58). Besides, BrP[5]L in 2(2-BPR)⊂BrP[5]L exhibited a 2D layer-like superstructure network with the neighboring layers stacking in a staggered packing mode; thus, no specific channels could be found in the structure (Fig. 5C). The PXRD pattern of BrP[5]L after adsorption of 2-BPR vapor was consistent with that simulated from 2-BPR⊂BrP[5]L (fig. S59), confirming that the uptake of 2-BPR resulted in a phase transition from nonporous BrP[5]Lβ to 2-BPR⊂BrP[5]L.

To prejudge the relative stability of BrP[5]L loaded with 1-bromoalkane and 2-bromoalkane, independent gradient model (IGM) analyses (visual study of weak interaction) were carried out (Fig. 5). The intermolecular binding isosurfaces revealed that the host-guest interactions of 1-BPR⊂BrP[5]L and 1-BBU⊂BrP[5]L are mainly concentrated in the center of the electron-rich cavity of BrP[5]L. Meanwhile, the guest molecules are fully encapsulated. In comparison, the areas of the binding isosurfaces between 2-BPR and BrP[5]L are centered mainly around the rims of the cavity, which binding mode is sustained primarily by the substituent groups of BrP[5]L. In addition, DSC experiments were conducted, and a broad endothermic peak ranging from 40° to 120°C was found in both 2-BPR⊂BrP[5]L and 2-BBU⊂BrP[5]L (figs. S60 and S61), representing the release of 2-BPR or 2-BBU molecules. As compared with the higher desorption temperatures and smaller endothermic ranges of both 1-BPR⊂BrP[5]L and 1-BBU⊂BrP[5]L as aforementioned, we can deduce that the in-cavity binding between 1-bromoalkanes and BrP[5]L with more suitable host-guest size/shape match will have higher thermostability than their corresponding 2-bromoalkanes–loaded structures.

Mixture vapor adsorption experiments of BrP[5]L

Given the different crystal structures and thermostabilities of BrP[5]L upon adsorption, we here investigated whether BrP[5]Lβ could separate 1-/2-bromoalkane isomers. First, a time-dependent solid-vapor (from an equimolar 1-BPR/2-BPR or 1-BBU/2-BBU mixture) sorption experiment was carried out. As shown in Fig. 6 (B and C), the uptake amounts of 1-BPR and 1-BBU increased with time and took about 2 and 5 hours to reach each saturation point, respectively. In sharp contrast to the single-component adsorption plots, the sorption of 2-bromoalkanes was negligible from beginning to end, and BrP[5]Lβ maintained its selectivity toward 1-bromoalkanes all along. Consistent with the crystal structures, the adsorption amounts of 1-BPR and 1-BBU were determined as nearly one 1-BPR or 1-BBU/BrP[5]L, which were also in good agreement with the single-component adsorption experiments as above mentioned (figs. S62 and S63). The PXRD patterns of BrP[5]Lβ after adsorption of the 1-/2-bromoalkane isomer mixture vapors matched well with that upon uptake of the single-component 1-bromoalkane vapors (Fig. 6, C and D). Gas chromatography (GC) tests showed that the purities of 1-BPR and 1-BBU adsorbed in BrP[5]Lβ were determined to be 98.1 and 99.0% (Fig. 6E and figs. S64 and S65), respectively, further supporting the remarkably high selectivity of BrP[5]Lβ for 1-bromoalkane isomers. Electrostatic potential maps for the complexes of 1-BPR⊂BrP[5]L and 1-BBU⊂BrP[5]L exhibited that electrons in the original electron-deficient 1-BPR and 1-BBU fully delocalized in the whole electron-rich cavity of BrP[5]Lβ upon adsorption (Fig. 6G), again confirming that the high selectivity not only arose from the stability of the newly formed crystal superstructure after guest adsorption but also came from the strong intermolecular interactions by the perfect size match between BrP[5]L and 1-bromoalkane isomers.

Fig. 6. Mixture vapor adsorption experiments of BrP[5]L.

Fig. 6.

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(A and B) Time-dependent BrP[5]Lβ solid-vapor adsorption plots for a 1:1 vapor mixture of (A) bromopropane isomers and (B) bromobutane isomers. (C) PXRD patterns of BrP[5]L: (I) original BrP[5]Lβ; (II) after adsorption of 2-BPR vapor, (III) simulated from the single-crystal structure of 2-BPR⊂BrP[5]L, (IV) after adsorption of 1-BPR vapor, (V) after adsorption of the 1-BPR and 2-BPR mixture vapor, and (VI) simulated from the single-crystal structure of 1-BPR⊂BrP[5]L. (D) PXRD patterns of BrP[5]L: (I) original BrP[5]Lβ, (II) after adsorption of 2-BBU vapor, (III) after adsorption of 1-BBU vapor, (IV) after adsorption of the 1-BBU and 2-BBU mixture vapor, and (V) simulated from the single-crystal structure of 1-BBU⊂BrP[5]L. (E) Relative amounts of 1- and 2-bromoalkane isomers adsorbed by BrP[5]Lβ over 7 hours as measured by GC. (F) Relative uptake of 1-BBU and 2-BBU by BrP[5]Lβ over 7 hours after BrP[5]L was recycled six times. (G) Electrostatic potential maps of 1-BPR, 1-BPR⊂BrP[5]L, 1-BBU, and 1-BBU⊂BrP[5]L revealing that electrons in the original electron-rich 1-bromoalkanes delocalized in the whole host-guest complexes because of strong intermolecular interactions. a.u., arbitrary units.

In industry, recyclability is one of the vital parameters to evaluate an adsorbent. We proved that BrP[5]Lβ with amorphous nature could be wholly regenerated by simply heating 1-BBU⊂BrP[5]L at 120°C under vacuum, as characterized by 1H NMR, TGA, and PXRD (figs. S66 to S69). Moreover, the newly formed BrP[5]Lβ still maintained its selectivity for 1-BBU vapor from an equal volume mixture of 1-BBU/2-BBU without any detectable degradation after recycling six times (Fig. 6F).

Controlled experiments by comparison with traditional pillararene

Given that BrP[5]Lβ exhibited high selectivity to 1-bromoalkane isomers, we were interested in finding some differences in the adsorption performance between BrP[5]Lβ and its counterpart macrocyclic arene of BrP[5]A (BrP[5]Aα) in traditional pillararenes (Fig. 7A). Therefore, controlled adsorption experiments by using BrP[5]Aα were carried out. Single-component solid-vapor adsorption experiments confirmed that the uptake amounts of 1-BPR, 2-BPR, 1-BBU, and 2-BBU could all be calculated as about one molecule per BrP[5]A at saturation (figs. S70 to S79), respectively. Consistent with BrP[5]Lβ, mixture vapor adsorption experiments revealed that BrP[5]Aα also exhibited an outstanding selectivity to 1-bromoalkane isomers (figs. S80 to S85). GC experiments demonstrated that the selectivities of BrP[5]Aα for 1-BPR and 1-BBU were 96.9 and 96.0%, respectively (Fig. 7B). Although the adsorptive selectivity of BrP[5]Aα toward 1-bromoalkane isomers is good, there are still substantial gaps in comparison with BrP[5]Lβ. To reveal the mechanism of the selectivity difference between BrP[5]A and BrP[5]L, we obtained single crystals of BrP[5]A loaded with 1-BBU (1-BBU⊂BrP[5]A) via a solution growth method (Fig. 7C). In line with 1-BBU⊂BrP[5]L, BrP[5]A molecules in 1-BBU⊂BrP[5]A were crystallized in the space group P-1 (triclinic) and formed a 1:1 host-guest complex with 1-BBU by the stabilization of multiple C─H···π (distances of 2.773, 2.689, 2.958, and 3.001 Å), C─H···O (distances of 2.993 and 3.057 Å), and C─H···Br (distances of 3.232 and 3.333 Å) interactions (fig. S86). Intriguingly, we found that BrP[5]L in 1-BBU⊂BrP[5]L exhibited a distinct guest-induced conformational change, where the DA value between the unsubstituted phenylene subunit and the pentagonal plane is 70.6°, in sharp contrast to the pillar-shaped molecular conformation of BrP[5]A in 1-BBU⊂BrP[5]A (fig. S87). Thus, the better adsorptive/guest selectivity than BrP[5]A is ascribed to the superior adaptability and tunability of the binding cavity in BrP[5]L macrocycle due to the free-rotation phenylene subunit.

Fig. 7. Controlled experiments by comparison with traditional pillararene.

Fig. 7.

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(A) Chemical structure of BrP[5]A. (B) Relative amounts of 1- and 2-bromoalkane isomers adsorbed by BrP[5]Aα over 7 hours as measured by GC. (C) Single-crystal structure of 1-BBU⊂BrP[5]A. (D) DFT-calculated rotational free energy comparison between the free-rotation phenylene subunit of P[5]L and a subunit of P[5]A.

In addition, the structural flexibility of P[5]Ls was also tested and proved by DFT analysis. Conformational free energies of P[5]L were calculated by rotating the DA of the unsubstituted phenylene subunit every 20° concerning the pentagonal plane (Fig. 7D). Taking a point-to-point comparison with the corresponding conformational free energy of traditional pillar[5]arene (P[5]A) by rotating one of its phenylene subunits, we can easily find that the rotation of the subunit in P[5]A is challenging, where the maximum rotational barrier reaches up to more than 80 kcal/mol, showing a barrier nearly 20-fold larger than that of P[5]L (about 4 kcal/mol). Besides, compared with the single low-energy state point at the pillar-shaped molecular conformation of P[5]A (90° DA), the energy changes of all points during the rotation in P[5]L were minor. These results indicated a markedly increased flexibility of macrocyclic backbone of P[5]L, allowing the free-rotation phenylene subunit to adopt a preferred perpendicular or tilted conformation and again confirmed the better tunability of the cavity size, endowing P[5]Ls with more potential for high selective guest adsorption as demonstrated by the aforementioned controlled experiments.

DISCUSSION

In conclusion, we have successfully developed a flexible macrocycle-based molecular-level adsorption material, amorphous solids of BrP[5]L, which can separate 1-/2-bromoalkane isomers with near-ideal selectivity. In conjunction with theoretical calculation and TG-DSC, single-crystal structures revealed that the adsorption selectivity mostly came from the higher thermostability of 1-bromoalkanes–loaded structures than its corresponding isomers-loaded structures, which could be further attributed to the perfect size/shape match between BrP[5]L and 1-bromoalkanes. Controlled experiments using its counterpart macrocyclic arene from traditional pillararenes demonstrated that BrP[5]Lβ had better sorting abilities by virtue of its superior structural adaptability and cavity-size tunability arising from the unsubstituted free-rotation phenylene subunit. In addition, the reversible transitions between the guest-free amorphous and the guest-containing crystalline state made BrP[5]L highly recyclable. On reflection, the novelty of this work can be summarized as follows: (i) We presented a family of skeleton-trimmed pillararene derivatives, leggero pillar[n]arene, and meanwhile, a nearly perfect separation of bromoalkane isomers using macrocycle-based molecular adsorbent is achieved; (ii) we proved that adsorption material without any porosity and crystallinity could also be greatly applied in molecular adsorptive separation; and (iii) new strategies to strengthen the structural adaptability and guest selectivity for traditional pillararenes have been put forward. Ongoing studies in our laboratory focus on constructing more supramolecular-level adsorptive separation materials based on the P[n]L family for applications in other demanding separations, such as sorting isotopes and chiral compounds.

MATERIALS AND METHODS

Materials availability

All reagents were purchased from commercial suppliers and used without further purification unless stated otherwise. The synthetic methods of P[5]L, EtP[5]L, EtP[6]L, P[5]L-1, and BrP[5]L are described in detail in the Supplementary Materials. 1-BPR, 2-BPR, 1-BBU, and 2-BBU were purchased from Sigma-Aldrich. Activated amorphous BrP[5]L, referred to as BrP[5]Lβ, was obtained by heating the thermodynamically favored guest-free crystalline structure of BrP[5]L, that is, BrP[5]Lα, under reduced pressure at 110°C for 6 hours.

Material characterization

1H and 13C NMR spectra were recorded at 298 K on a Bruker AVANCE III 400-MHz instrument at room temperature. Chemical shifts were referenced to tetramethylsilane. Mass spectra were recorded on Bruker Daltonics Autoflex Speed Series: High-Performance MALDI-TOF Systems and a Bruker Agilent1290 micrOTOF-Q II high-resolution MS instrument. PXRD measurements were collected on a PANalytical B.V. Empyrean powder diffractometer operating at 40 kV/30 mA using the Cu Kα line (λ = 1.5418 Å). Following procedures previously described in (41), data were measured over the range 5° to 40° in 5°/min steps over 7 min. Single-crystal XRD data were measured by a Bruker D8 Venture diffractometer using the ω-scan mode with graphite-monochromator Mo Kα radiation (λ = 0.71073 Å) and Ga Kα (λ = 1.34139 Å). The structures were solved with SHELXD (42), with SHELXT (43), or by the direct methods with SHELXS-2014 (44); refined by full-matrix least squares on |F|2 by SHELXL (45); and interfaced through the program Olex2 (46). TGA was carried out using a simultaneous thermal analyzer 449 F3 analyzer (NETZSCH Instruments) with an automated vertical overhead thermobalance. The samples were heated at 10°C/min using N2 as the protective gas. DSC analysis was done on a DSC Q20 at a heating rate of 10°C/min at a nitrogen atmosphere. Low-pressure gas adsorption measurements were performed on a Micromeritics Accelerated Surface Area and Porosimetry System 2020 surface area analyzer. Samples were degassed under dynamic vacuum for 12 hours at 100°C before each measurement. N2 isotherms were measured using a liquid nitrogen bath (77 K).

Vapor-phase adsorption measurements

For each solid-vapor sorption and fractionation experiment, an open 0.5-ml vial containing 3.0 mg of activated BrP[5]L adsorbent (BrP[5]Lβ) was placed in a sealed 2-ml vial containing 0.03 ml of solvent or solvent mixture (50:50, v/v). Relative uptake amount in the amorphous solids of BrP[5]L was determined by 1H NMR integrals of corresponding proton signals by completely dissolving the organic powders in CDCl3. GC characterizations were also performed to determine the relative uptake amounts of 1-/2-bromoalkane isomers more accurately. Desorption experiments after saturation were carried out by TGA and DSC.

Theoretical calculations

All calculations were performed by DFT using the B3LYP hybrid function combined with 6-31G(d,p) basis set under Gaussian G09. Using single-crystal superstructures as input files, IGM analyses (47) were carried out by Multiwfn 3.6 program (48) through function 20 (visual study of weak interaction) and visualized using Visual Molecular Dynamics software (49).

Acknowledgments

Funding: This work was supported by the National Natural Science Foundation of China (grant nos. 52173200 and 21871108), the China Postdoctoral Science Foundation (grant no. BX2021112), and Jilin Province-University Cooperative Construction Project–Special Funds for New Materials (grant no. SXGJSF2017-3).

Author contributions: Conceptualization: J.-R.W. and Y.-W.Y. Methodology: J.-R.W. and G.W. Investigation: J.-R.W. and G.W. Visualization: J.-R.W. and Y.-W.Y. Supervision: Y.-W.Y. Writing (original draft): J.-R.W., G.W., D.L., and D.D. Writing (review and editing): Y.-W.Y.

Competing interests: The authors declare that they have no competing interests.

Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. X-ray crystallographic data reported here are listed in the Supplementary Materials and archived at the Cambridge Crystallographic Data Centre under reference numbers CCDC 2041500, 2041451, 2041449, 2041446, 2041448, 2041450, 2124278, 2124280, 2124276, 2124288, and 2124291.

Supplementary Materials

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Supplementary Methods

Supplementary Data and Figures

Figs. S1 to S87

Tables S1 to S4

References

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Other Supplementary Material for this manuscript includes the following:

Dataset files

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REFERENCES AND NOTES

  • 1.Hua B., Ding Y., Alimi L. O., Moosa B., Zhang G., Baslyman W. S., Sessler J., Khashab N. M., Tuning the porosity of triangular supramolecular adsorbents for superior haloalkane isomer separations. Chem. Sci. 12, 12286–12291 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Zhou Y., Jie K., Zhao R., Li E., Huang F., Highly selective removal of trace isomers by nonporous adaptive pillararene crystals for chlorobutane purification. J. Am. Chem. Soc. 142, 6957–6961 (2020). [DOI] [PubMed] [Google Scholar]
  • 3.Bao Z., Chang G., Xing H., Krishna R., Ren Q., Chen B., Potential of microporous metal-organic frameworks for separation of hydrocarbon mixtures. Energ. Environ. Sci. 9, 3612–3641 (2016). [Google Scholar]
  • 4.Eddaoudi M., Kim J., Rosi N., Vodak D., Wachter J., O’Keeffe M., Yaghi Omar M., Systematic design of pore size and functionality in isoreticular MOFs and their application in methane storage. Science 295, 469–472 (2002). [DOI] [PubMed] [Google Scholar]
  • 5.Cai G., Yan P., Zhang L., Zhou H.-C., Jiang H.-L., Metal-organic framework-based hierarchically porous materials: Synthesis and applications. Chem. Rev. 121, 12278–12326 (2021). [DOI] [PubMed] [Google Scholar]
  • 6.Li J.-R., Sculley J., Zhou H.-C., Metal-organic frameworks for separations. Chem. Rev. 112, 869–932 (2012). [DOI] [PubMed] [Google Scholar]
  • 7.Yu M., Noble R. D., Falconer J. L., Zeolite membranes: Microstructure characterization and permeation mechanisms. Acc. Chem. Res. 44, 1196–1206 (2011). [DOI] [PubMed] [Google Scholar]
  • 8.Chen L.-H., Sun M.-H., Wang Z., Yang W., Xie Z., Su B.-L., Hierarchically structured zeolites: From design to application. Chem. Rev. 120, 11194–11294 (2020). [DOI] [PubMed] [Google Scholar]
  • 9.Dusselier M., Davis M. E., Small-pore zeolites: Synthesis and catalysis. Chem. Rev. 118, 5265–5329 (2018). [DOI] [PubMed] [Google Scholar]
  • 10.Jie K., Zhou Y., Sun Q., Li B., Zhao R., Jiang D.-e., Guo W., Chen H., Yang Z., Huang F., Dai S., Mechanochemical synthesis of pillar[5]quinone derived multi-microporous organic polymers for radioactive organic iodide capture and storage. Nat. Commun. 11, 1086 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Lee J.-S. M., Cooper A. I., Advances in conjugated microporous polymers. Chem. Rev. 120, 2171–2214 (2020). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Wu D., Xu F., Sun B., Fu R., He H., Matyjaszewski K., Design and preparation of porous polymers. Chem. Rev. 112, 3959–4015 (2012). [DOI] [PubMed] [Google Scholar]
  • 13.Chen W., Chen P., Zhang G., Xing G., Feng Y., Yang Y.-W., Chen L., Macrocycle-derived hierarchical porous organic polymers: Synthesis and applications. Chem. Soc. Rev. 50, 11684–11714 (2021). [DOI] [PubMed] [Google Scholar]
  • 14.Côté Adrien P., Benin Annabelle I., Ockwig Nathan W., O’Keeffe M., Matzger Adam J., Yaghi Omar M., Porous, crystalline, covalent organic frameworks. Science 310, 1166–1170 (2005). [DOI] [PubMed] [Google Scholar]
  • 15.Feng X., Ding X., Jiang D., Covalent organic frameworks. Chem. Soc. Rev. 41, 6010–6022 (2012). [DOI] [PubMed] [Google Scholar]
  • 16.Geng K., He T., Liu R., Dalapati S., Tan K. T., Li Z., Tao S., Gong Y., Jiang Q., Jiang D., Covalent organic frameworks: Design, synthesis, and functions. Chem. Rev. 120, 8814–8933 (2020). [DOI] [PubMed] [Google Scholar]
  • 17.Zhang Y. Y., Duan J. Y., Ma D., Li P. F., Li S. W., Li H. W., Zhou J. W., Ma X. J., Feng X., Wang B., Three-dimensional anionic cyclodextrin-based covalent organic frameworks. Angew. Chem. Int. Ed. 56, 16313–16317 (2017). [DOI] [PubMed] [Google Scholar]
  • 18.Li X., Xu H.-S., Leng K., Chee S. W., Zhao X., Jain N., Xu H., Qiao J., Gao Q., Park I.-H., Quek S. Y., Mirsaidov U., Loh K. P., Partitioning the interlayer space of covalent organic frameworks by embedding pseudorotaxanes in their backbones. Nat. Chem. 12, 1115–1122 (2020). [DOI] [PubMed] [Google Scholar]
  • 19.He Y., Xiang S., Chen B., A microporous hydrogen-bonded organic framework for highly selective C2H2/C2H4 separation at ambient temperature. J. Am. Chem. Soc. 133, 14570–14573 (2011). [DOI] [PubMed] [Google Scholar]
  • 20.Hisaki I., Xin C., Takahashi K., Nakamura T., Designing hydrogen-bonded organic frameworks (HOFs) with permanent porosity. Angew. Chem. Int. Ed. 58, 11160–11170 (2019). [DOI] [PubMed] [Google Scholar]
  • 21.Lin Y., Jiang X., Kim S. T., Alahakoon S. B., Hou X., Zhang Z., Thompson C. M., Smaldone R. A., Ke C., An elastic hydrogen-bonded cross-linked organic framework for effective iodine capture in water. J. Am. Chem. Soc. 139, 7172–7175 (2017). [DOI] [PubMed] [Google Scholar]
  • 22.Song N., Kakuta T., Yamagishi T.-a., Yang Y.-W., Ogoshi T., Molecular-scale porous materials based on pillar[n]arenes. Chem 4, 2029–2053 (2018). [Google Scholar]
  • 23.Tan L. L., Li H. W., Tao Y. C., Zhang S. X. A., Wang B., Yang Y. W., Pillar[5]arene-based supramolecular organic frameworks for highly selective CO2-capture at ambient conditions. Adv. Mater. 26, 7027–7031 (2014). [DOI] [PubMed] [Google Scholar]
  • 24.Patil R. S., Drachnik A. M., Kumari H., Barnes C. L., Deakyne C. A., Atwood J. L., Solvent-induced manipulation of supramolecular organic frameworks. Cryst. Growth Des. 15, 2781–2786 (2015). [Google Scholar]
  • 25.Tozawa T., Jones J. T. A., Swamy S. I., Jiang S., Adams D. J., Shakespeare S., Clowes R., Bradshaw D., Hasell T., Chong S. Y., Tang C., Thompson S., Parker J., Trewin A., Bacsa J., Slawin A. M. Z., Steiner A., Cooper A. I., Porous organic cages. Nat. Mater. 8, 973–978 (2009). [DOI] [PubMed] [Google Scholar]
  • 26.Mitra T., Jelfs K. E., Schmidtmann M., Ahmed A., Chong S. Y., Adams D. J., Cooper A. I., Molecular shape sorting using molecular organic cages. Nat. Chem. 5, 276–281 (2013). [DOI] [PubMed] [Google Scholar]
  • 27.He A., Jiang Z., Wu Y., Hussain H., Rawle J., Briggs M. E., Little M. A., Livingston A. G., Cooper A. I., A smart and responsive crystalline porous organic cage membrane with switchable pore apertures for graded molecular sieving. Nat. Mater. 21, 463–470 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Atwood Jerry L., Barbour Leonard J., Jerga A., Schottel Brandi L., Guest transport in a nonporous organic solid via dynamic van der Waals cooperativity. Science 298, 1000–1002 (2002). [DOI] [PubMed] [Google Scholar]
  • 29.Thallapally P. K., Peter McGrail B., Dalgarno S. J., Schaef H. T., Tian J., Atwood J. L., Gas-induced transformation and expansion of a non-porous organic solid. Nat. Mater. 7, 146–150 (2008). [DOI] [PubMed] [Google Scholar]
  • 30.Jie K., Zhou Y., Li E., Li Z., Zhao R., Huang F., Reversible iodine capture by nonporous pillar[6]arene crystals. J. Am. Chem. Soc. 139, 15320–15323 (2017). [DOI] [PubMed] [Google Scholar]
  • 31.Jie K., Zhou Y., Li E., Huang F., Nonporous adaptive crystals of pillararenes. Acc. Chem. Res. 51, 2064–2072 (2018). [DOI] [PubMed] [Google Scholar]
  • 32.Zhou Y., Jie K., Zhao R., Huang F., Supramolecular-macrocycle-based crystalline organic materials. Adv. Mater. 32, 1904824 (2020). [DOI] [PubMed] [Google Scholar]
  • 33.Lei S. N., Xiao H. Y., Zeng Y., Tung C. H., Wu L. Z., Cong H., BowtieArene: A dual macrocycle exhibiting stimuli-responsive fluorescence. Angew. Chem. Int. Ed. 59, 10059–10065 (2020). [DOI] [PubMed] [Google Scholar]
  • 34.Luo D., Tian J., Sessler J. L., Chi X., Nonporous adaptive calix[4]pyrrole crystals for polar compound separations. J. Am. Chem. Soc. 143, 18849–18853 (2021). [DOI] [PubMed] [Google Scholar]
  • 35.Wu J. R., Li B., Yang Y. W., Separation of bromoalkanes isomers by nonporous adaptive crystals of leaning pillar[6]arene. Angew. Chem. Int. Ed. 59, 2251–2255 (2020). [DOI] [PubMed] [Google Scholar]
  • 36.Wu J.-R., Yang Y.-W., Geminiarene: Molecular scale dual selectivity for chlorobenzene and chlorocyclohexane fractionation. J. Am. Chem. Soc. 141, 12280–12287 (2019). [DOI] [PubMed] [Google Scholar]
  • 37.Ogoshi T., Yamagishi T.-a., Nakamoto Y., Pillar-shaped macrocyclic hosts pillar[n]arenes: New key players for supramolecular chemistry. Chem. Rev. 116, 7937–8002 (2016). [DOI] [PubMed] [Google Scholar]
  • 38.Xia D., Wang P., Ji X., Khashab N. M., Sessler J. L., Huang F., Functional supramolecular polymeric networks: The marriage of covalent polymers and macrocycle-based host-guest interactions. Chem. Rev. 120, 6070–6123 (2020). [DOI] [PubMed] [Google Scholar]
  • 39.Li Z., Yang Y.-W., Functional materials with pillarene struts. Acc. Mater. Res. 2, 292–305 (2021). [Google Scholar]
  • 40.Wu J.-R., Cai Z., Wu G., Dai D., Liu Y.-Q., Yang Y.-W., Bottom-up solid-state molecular assembly via guest-induced intermolecular interactions. J. Am. Chem. Soc. 143, 20395–20402 (2021). [DOI] [PubMed] [Google Scholar]
  • 41.Zhou Y., Jie K., Zhao R., Li E., Huang F., Cyclic ether contaminant removal from water using nonporous adaptive pillararene crystals via host-guest complexation at the solid-solution interface. Research 2019, 5406365 (2019). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Sheldrick G. M., Experimental phasing with SHELXC/D/E: Combining chain tracing with density modification. Acta Crystallogr. D Biol. Crystallogr. 66, 479–485 (2010). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Sheldrick G. M., SHELXT - Integrated space-group and crystal-structure determination. Acta Crystallogr. A Found. Adv. 71, 3–8 (2015). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Sheldrick G. M., A short history of SHELX. Acta Crystallogr. 64, 112–122 (2008). [DOI] [PubMed] [Google Scholar]
  • 45.Sheldrick G. M., Crystal structure refinement with SHELXL. Acta Crystallogr. C Struct. Chem. 71, 3–8 (2015). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Dolomanov O. V., Bourhis L. J., Gildea R. J., Howard J. A. K., Puschmann H., Olex2: A complete structure solution, refinement and analysis program. J. Appl. Cryst. 42, 339–341 (2009). [Google Scholar]
  • 47.Lefebvre C., Rubez G., Khartabil H., Boisson J. C., Contreras-Garcia J., Henon E., Accurately extracting the signature of intermolecular interactions present in the NCI plot of the reduced density gradient versus electron density. Phys. Chem. Chem. Phys. 19, 17928–17936 (2017). [DOI] [PubMed] [Google Scholar]
  • 48.Lu T., Chen F. W., Multiwfn: A multifunctional wavefunction analyzer. J. Comput. Chem. 33, 580–592 (2012). [DOI] [PubMed] [Google Scholar]
  • 49.Humphrey W., Dalke A., Schulten K., VMD: Visual Molecular Dynamics. J. Mol. Graph. 14, 33–38 (1996). [DOI] [PubMed] [Google Scholar]
  • 50.Wu J.-R., Mu A. U., Li B., Wang C.-Y., Fang L., Yang Y.-W., Desymmetrized leaning pillar[6]arene. Angew. Chem. Int. Ed. 57, 9853–9858 (2018). [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Methods

Supplementary Data and Figures

Figs. S1 to S87

Tables S1 to S4

References

Click here for additional data file. (7.9MB, pdf)

Dataset files

Click here for additional data file. (1.6MB, zip)

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