Soft Hydrogen-Bonded Organic Frameworks Constructed Using a Flexible Organic Cage Hinge

Soft porous crystals combine flexibility and porosity, allowing them to respond structurally to external physical and chemical environments. However, striking the right balance between flexibility and sufficient rigidity for porosity is challenging, particularly for molecular crystals formed by using weak intermolecular interactions. Here, we report a flexible oxygen-bridged prismatic organic cage molecule, Cage-6-COOH, which has three pillars that exhibit “hinge-like” rotational motion in the solid state. Cage-6-COOH can form a range of hydrogen-bonded organic frameworks (HOFs) where the “hinge” can accommodate a remarkable 67° dihedral angle range between neighboring units. This stems both from flexibility in the noncovalent hydrogen-bonding motifs in the HOFs and the molecular flexibility in the oxygen-linked cage hinge itself. The range of structures for Cage-6-COOH includes two topologically complex interpenetrated HOFs, CageHOF-2α and CageHOF-2β. CageHOF-2α is nonporous, while CageHOF-2β has permanent porosity and a surface area of 458 m2 g–1. The flexibility of Cage-6-COOH allows this molecule to rapidly transform from a low-crystallinity solid into the two crystalline interpenetrated HOFs, CageHOF-2α and CageHOF-2β, under mild conditions simply by using acetonitrile or ethanol vapor, respectively. This self-healing behavior was selective, with the CageHOF-2β structure exhibiting structural memory behavior.


■ INTRODUCTION
Soft porous crystals have attracted much interest since they were proposed as third-generation porous framework materials by Kitagawa and co-workers in 1998. 1,2−7 Most soft porous crystals reported in the literature are coordination frameworks, 6,8−11 such as the metal−organic frameworks (MOFs), MIL-53, 12 and MIL-88, 13,14 where the secondary building units and organic ligands can rotate to reshape the pores though "hinge-type" rotation. 15While there are now a few examples of MOFs that exhibit this type of structural flexibility, reports of flexible MOFs with switchable porosity are still somewhat rare compared to rigid MOFs. 16By contrast, molecular crystals, which do not contain extended coordination bonded frameworks, can exhibit more profound dynamic behavior: for example, to allow the encapsulation of guests such as enzymes. 17However, dynamic flexibility frequently results in a permanent loss of porosity in molecular crystals.
−26 In most cases, the flexibility of these HOFs can be explained in large part by related rotations around single carbon−carbon bonds (Figure 1a).A different approach is to mimic the "hinge-type" rotation used to tune the pore size in MOFs, which is synthetically tunable 27 and, to a degree, computationally predictable. 15owever, translating this approach into the area of HOFs requires new three-dimensional (3-D) building blocks that feature "hinge-like" rotatable groups.Such building blocks are rare, particularly for porous HOFs where building block rigidity has tended to be a prerequisite to prevent HOFs from collapsing into nonporous structures. 28,29ere, we prepared soft porous organic crystals using a flexible oxygen-bridged cage molecule (Cage-6-COOH, Figure 1b).Cage-6-COOH contains six trigonal prismatically arranged carboxylic acid groups and somewhat flexible oxygen bridges that allow the hinge-like rotation of trigonally arranged aromatic pillars.This conformational flexibility endows Cage-6-COOH with rich structural behavior in the solid state.We found that Cage-6-COOH can crystallize to form both a 3-fold (CageHOF-2α) and 2-fold (CageHOF-2β) interpenetrated HOF, along with five other solvated HOFs.In combination, this diverse family of Cage-6-COOH crystal structures revealed the extensive conformational flexibility of the aromatic pillars and their ability to rotate from 90°degrees in CageHOF-2β to 157°degrees in CageHOF-2•H 2 O in a hinge-like rotation.This profound flexibility of Cage-6-COOH enabled the soft HOF to self-heal, transforming into crystalline solids upon treatment with organic vapors.Moreover, CageHOF-2α switches to CageHOF-2β in response to ethanol vapor, which exhibits permanent porosity and has a Brunauer−Emmett−Teller (BET) surface area (SA BET ) of 458 m 2 g −1 , as measured using N 2 adsorption at 77 K.

■ RESULTS AND DISCUSSION
Triangular prismatic-shaped molecules are a common polyhedral motif for constructing 3-D extended frameworks, including materials with flexible structures 14 and high storage capacities. 305,36 Here, we explore the third approach, which uses oxygen-bridged trigonal prismatic organic cages 37,38 (Figure 1b).An advantage of oxygen-bridged organic cages is their stability and excellent tolerance to a wide range of synthetic conditions and modifications, which has yielded a rich family of organic cages with diverse functions and geometries.40−46 We synthesized the carboxylic acid-functionalized cage compound, Cage-6-COOH, by hydrolyzing the cyano groups of a previously reported cage, Cage-6-CN (Schemes S1−S4).40 We confirmed the formation of Cage-6-COOH using 1 H, 13 C, HSQC (Figures S2−S4), and HMBC spectroscopy (Figure S5), along with MALDI-TOF mass spectroscopy.In the 1 H NMR spectrum, a singlet corresponding to the proton of the carboxylic acid group was observed at a low field (δ = 13.2 ppm), indicating the successful conversion of Cage-6-CN to Cage-6-COOH (Figure S2).We also observed two singlets at δ = 8.78 and 6.76 ppm, assigned to the two aromatic protons, indicating that Cage-6-COOH adopts a high D 3h -symmetric structure in solution.
We confirmed the bulk-phase purity of CageHOF-2α by powder X-ray diffraction (PXRD) using a Pawley refinement of the CH 3 CN-solvated material loaded in a capillary (see Figure S10 for refinement details).The Pawley refinement and the simulated PXRD pattern for CageHOF-2α indicate that the CH 3 CN-solvated crystalline sample was phase-pure.Cage-HOF-2α contains three different and modestly sized (<10 Å) triangular-shaped solvent-filled pores (Figure 2d,e), so we next investigated its stability to activation.However, all attempts to remove the solvent from the crystal pores, including heating (Figures S11 and S12) and supercritical CO 2 drying (scCO 2 , Figure S13), caused CageHOF-2α to transform into a lowcrystallinity solid (referred to as CageHOF-2) that was nonporous based on N 2 sorption at 77 K (Figure S14).We used variable-temperature (VT) PXRD measurement to  S15), which we attribute to the denser packing of Cage-6-COOH layers in the CageHOF-2α crystal structure (Figure S16).
Next, we expanded our crystallization screen and discovered a new polymorph, CageHOF-2β, that was formed by crystallizing Cage-6-COOH from ethanol (EtOH) after leaving a solution to evaporate at 343 K.During the crystallization, we observed spindle-like crystals on the surface of the vial (Figure S8).Due to the small crystal size and weak diffraction, SCXRD quality was limited but sufficient to determine the crystal packing of Cage-6-COOH.As shown in Figure 3 are not all planar, and the aromatic pillars have profoundly different orientations.For comparison, the dihedral angles in CageHOF-2α range between 116°and 126°, while the dihedral angles in CageHOF-2β range between 90°and 143°.In addition, there are two interpenetrated HOF networks in the extended CageHOF-2β structure compared to three in CageHOF-2α.We attribute these differences to the hinge-like rotation of the Cage-6-COOH pillars since the change in solvent did not appear to disrupt the hydrogen-bonding interactions between the cage molecules.
We performed a refinement on the PXRD of EtOH-solvated CageHOF-2β to confirm its phase purity.(See Figure 3e for the Pawley refinement and Figure S17 for the Rietveld refinement.)The excellent similarity between the experimental PXRD data and the PXRD refinements indicated that the bulk CageHOF-2β sample was phase-pure and that it closely matched the single-crystal structure.
Properties of CageHOF-2β.We first investigated the stability of CageHOF-2β by in situ VT-PXRD analysis (Figures S18 and S19).No significant changes were observed in the VT-PXRD patterns of CageHOF-2β while increasing the temperature from 303 to 433 K or upon recooling the sample to room temperature, indicating that CageHOF-2β has good thermal stability (Figure S18).From the VT-PXRD study, we also observed that CageHOF-2β contracts along the a and b unit cell axes during heating while expanding along the c unit cell axis (Figure S20).We attribute this to the hydrogenbonding interactions between Cage-6-COOH molecules reorganizing into a more planar geometry along the c unit cell axis, which enables the Cage-6-COOH molecules to pack more closely along the a and b unit cell axes (Figure S21).
This thermal stability encouraged us to obtain crystalline porous materials by careful desolvation treatment for CageHOF-2β.Before studying the porosity of CageHOF-2β, we first exchanged the EtOH crystallization solvent with acetone and then n-pentane over 2 days, noting that n-pentane is the most volatile and least likely to interact strongly with the pore walls (see SI Section 4 for details).Then, we activated the pores under a dynamic vacuum at room temperature.Unlike CageHOF-2α, the crystallinity of CageHOF-2β appeared to be preserved after activating the crystal, according to the PXRD patterns (Figure 3e and Figure S22).However, the NMR spectrum indicates that the activated CageHOF-2β still contained a trace amount of EtOH solvent (3.5 wt %, Figure S23).Thermogravimetric analysis (TGA, Figure S24) showed a 5% weight loss before 450 °C, in broad agreement with the NMR data.
Next, we recorded an N 2 sorption isotherm for the activated CageHOF-2β at 77 K.This gave a type-I sorption isotherm with a sharp uptake over the low-pressure range (P/P 0 = 0− 0.01), indicating that CageHOF-2β possesses micropores (Figure 3f).The SA BET also revealed a surface area of 410 m 2 g −1 (Figures S25), which is similar to that of other soft porous HOFs reported in the literature. 22,24,47We also recorded a PXRD pattern of CageHOF-2β after the N 2 sorption isotherm, which confirmed the good stability of CageHOF-2β during this sorption measurement (Figure S26).
The crystal structures of CageHOF-2•DMAc, CageHOF-2• NMP, and CageHOF-2•DESO are isostructural with respect to the crystal packing of Cage-6-COOH, despite the differences between the physical properties of the crystallization solvents (Figure S34).In total, we measured seven SCXRD structures of Cage-6-COOH during this study.In combination, these structures exemplify the profound hingelike flexibility of the oxygen bridges and hydrogen-bonded interactions (Figure 4, Figures S35−S37, and Tables S11− S13) and the apparent rigidity of the aligned 1,3,5-substituted aromatic rings in the cage core (Table S14).Indeed, we found that the dihedral angle (Φ in Figure 4) could rotate from 90°i n CageHOF-2β to up to 157°in CageHOF-2•H 2 O. Furthermore, the three aromatic pillars in Cage-6-COOH appear to be independently flexible and typically have different conformations in each structure, highlighting the soft nature of these frameworks (Table S11).We used relaxed scan density functional theory (DFT) calculations to investigate the flexibility of Cage-6-COOH.These DFT calculations revealed that the lowest-energy conformer had dihedral angles of around 120°.However, the energy required to rotate the pillars of Cage-6-COOH by 60°from 120°was approximately 6.4 kcal mol −1 (Figure S38 and Section 1.2.7 for full details), which is within the usual energetic range of polymorphism. 49ere, this hinge-like rotation in Cage-6-COOH adapts to accommodate guests in the resulting crystals.It is therefore comparable to prototypical MOFs such as MIL-53, which has pores that can expand and contract using a "hinge-type" rotation, 4,6 albeit through a different process.
Furthermore, we performed molecular dynamics (MD) simulations to investigate the flexibility of Cage-6-COOH.We performed these MD simulations using the RASPA software package and a 2 × 2 × 3 supercell generated using the SCXRD of CageHOF-2α (see Section 1.2.7 for details and Figure S39).These MD simulations indicate that Cage-6-COOH molecules exhibit "hinge-like" rotational motion in CageHOF-2α (Supporting Information Video 1).At the same time, the packing of the Cage-6-COOH layers in the structure appears to be rigid (Supporting Information Video 2).This observation agrees well with the VT-PXRD measurements performed using the CH 3 CN-solvated CageHOF-2α (Figures S11, S12, and S15), which indicated that the packing of Cage-6-COOH layers along the c unit cell axis remained essentially unchanged during the VT-PXRD measurement.We attribute the rigidity of hydrogen-bonded layers of Cage-6-COOH in CageHOF-2α to the order we observed in the desolvated PXRD patterns (Figure S13).
Self-Healing Properties of Cage-6-COOH.Although HOFs can recover their crystallinity via recrystallization from solution, HOFs that self-heal via solid-state structural transformations are rare. 18,20,47The profound flexibility of Cage-6-COOH motivated us to study its self-healing properties.To do this, we conducted organic vapor sorption experiments by exposing an activated, solvent-free, activated CageHOF-2 powder to CH 3 CN vapor.In the CH 3 CN sorption isotherm, we observed a stepwise increase in the uptake (Figure 5a) with a gradual increase over the low-pressure range, followed by a steep increase in the uptake at P/P 0 = 0.43.The pores then appeared to saturate by about P/P 0 = 0.85.From the CH 3 CN isotherm, we calculated that the experimental pore volumes of the activated CageHOF-2 powder were 0.12 cm 3 g −1 at P/P 0 = 0.41, 0.23 cm 3 g −1 at P/P 0 = 0.68, and 0.25 cm 3 g −1 at P/P 0 = 0.93.These pore volumes are below the theoretical uptake of CageHOF-2α of 0.40 cm 3 g −1 calculated using a 2.5 Å probe; however, this can be rationalized by the poor structural stability of activated CageHOF-2α.PXRD patterns recorded after CH 3 CN vapor exposure indicated that the CageHOF-2 powder had switched to CageHOF-2α with high crystallinity.Further PXRD experiments suggested that this transformation was reversible; that is, the regenerated CageHOF-2α crystal transformed to CageHOF-2 powder again after removing the CH 3 CN (Figures S40−S42).We also observed this type of gate open behavior during a CO 2 adsorption isotherm recorded at 195 K (Figure S43), with the pore volume increasing from 0.024 cm 3 g −1 at P/P 0 = 0.21 to 0.185 cm 3 g −1 at P/P 0 = 0.96.
After the CH 3 CN vapor sorption isotherm, we used the same sample for an EtOH vapor sorption isotherm after degassing the material at 333 K for 12 h.Again, we observed a gate-opening-type sorption isotherm, with a sharp increase occurring from about P/P 0 = 0.35, indicating the existence of a phase transformation (Figure 5b).In this case, the sorption process was irreversible until the fourth cycle.After that, the saturation point gradually moved to the low-pressure range, suggesting that the material transforms into a porous metastable phase step by step over successive adsorption experiments, as verified by PXRD analysis (Figure S44).From the EtOH isotherm, we calculated that the experimental pore volume of the CageHOF-2 powder was 0.197 cm 3 g −1 at P/P 0 = 0.97, which is close to the theoretical value of CageHOF-2β of 0.22 cm 3 g −1 calculated using a 2.5 Å probe.A further PXRD study confirmed that activated CageHOF-2 powder transformed into the porous CageHOF-2β phase upon treatment with EtOH vapor (Figure S41).Remarkably, this structural transformation appeared to be complete after 5 min under saturated EtOH vapor at room temperature, as indicated by a dynamic PXRD study (Figure S45).This switching behavior is advantageous for the scale-up preparation of CageHOF-2β with improved porosity (458 m 2 g −1 , Figures S46 and S47).We propose that the fast crystalline transformation is due to the synergistic effect of the flexible oxygen bridges in Cage-6-COOH and flexible carboxylic acid hydrogen-bond dimers.Notably, we could not transform CageHOF-2β into CageHOF-2α after exposing CageHOF-2β to CH 3 CN vapor, suggesting that activated CageHOF-2 powder exhibits a structural "memory" behavior, as observed in some soft porous MOF materials. 2,50e screened the self-healing behavior of activated CageHOF-2 powder in response to different organic solvents, which suggests that the self-healing behavior strongly correlates with the type and functionality of the solvent (Figure S48).For example, we found that a trace amount of THF liquid cleanly transformed activated CageHOF-2 powder into highly crystalline CageHOF-2•THF (Figures S49−S51).By contrast, MeOH transformed activated CageHOF-2 powder into CageHOF-2β, whereas solvents without hydrogen-bond donor and acceptor atoms, such as hexane and toluene, had no apparent effect on the structure of the material (Figure S48).In addition, we found that after being immersed in water for several days, CageHOF-2α transformed to CageHOF-2• H 2 O. Interestingly, CageHOF-2•THF and CageHOF-2•H 2 O could then be transformed to CageHOF-2β using EtOH (Figures S52−S54).

■ CONCLUSIONS
We have prepared a soft porous crystal using a flexible cage molecule, Cage-6-COOH.This cage molecule is decorated with six carboxylic acid groups, and it features a 3-D arrangement of rotationally flexible oxygen bridges that allow it to adapt its conformation in the solid state via hinge-like rotational motion.We found seven crystal structures of Cage-6-COOH, including topologically complex 3-D HOFs featuring 3-fold (CageHOF-2α) and 2-fold (CageHOF-2β) interpenetration.Of these HOFs, CageHOF-2β alone had permanent solid-state porosity and an SA BET of 458 m 2 g −1 .
CageHOF-2α collapsed into the low-crystallinity CageHOF-2 powder during activation, as do many other interpenetrated HOFs, except for a few examples. 31,32,51However, the hingelike flexibility of Cage-6-COOH enabled the CageHOF-2 powder to self-heal to recover its CageHOF-2α structure using solvent vapor or to transform selectively into porous CageHOF-2β.These structural transformations were fast and complete within 5 min, with the crystalline solids exhibiting structural memory behavior during vapor sorption experiments.
Taken together, these results outline a new strategy to generate soft, crystalline, and porous HOFs using organic cage molecules.These soft porous crystalline HOFs mimic the structural behavior of certain MOFs, without the requirement of a coordination network.This lack of a coordination network seems to help Cage-6-COOH to rapidly self-heal and undergo rapid and profound structural transformations, even under mild conditions (5 min, solvent vapor, room temperature).This suggests a possible unique advantage of soft porous molecular systems over bonded framework materials.Further exploration of this approach, for example, by constructing HOFs with the molecular hinge motifs found in molecular machines, 52 might help HOFs to mimic even more complex structural behavior found in nature that is also underpinned by "hinge-type" rotation.

Figure 1 .
Figure 1.Representative flexible molecules used in the formation of soft HOFs.(a) Most examples involve carbon−carbon single bondbased rotation.(b) Here, we exploit "hinge-like" rotation for cagebased HOF linkers.

Figure 2 .
Figure 2. Crystal structures of CageHOF-2α.(a) The structure of Cage-6-COOH can be represented topologically as a triangular prism.(b) Top view and (c) side view of CageHOF-2α under the noninterpenetrated acs topology.Atom colors: C, white; N, blue; and O, red.H atoms are omitted for clarity.(d) Top view and (e) side view CageHOF-2α under the 3-fold interpenetrated acs topology, where the triangular prisms represent Cage-6-COOH and the cage nodes belonging to the different nets colored here in green, red, and blue.

Figure 4 .
Figure 4. Scheme illustrating the hinge-like motion of Cage-6-COOH in various crystal structures.The dihedral angles of the pillar rings change from 90°to 157°in these crystal structures. 52 CCDC 2253690−2253694 and 2290410−2290411 contain the supplementary crystallographic data for this paper.These data can be obtained free of charge via www.ccdc.cam.ac.uk/ data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.Department of Chemistry and Materials Innovation Factory and Leverhulme Research Centre for Functional Materials Design, University of Liverpool, Liverpool L7 3NY, U.K.; orcid.org/0000-0001-6462-9340Lei Wei − School of Physical Science and Technology, ShanhaiTech University, Shanghai 201210, China Chengxi Zhao − Department of Chemistry and Materials Innovation Factory, University of Liverpool, Liverpool L7 3NY, U.K.; Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China Hang Qu − Department of Chemistry and Materials Innovation Factory, University of Liverpool, Liverpool L7 3NY, U.K.; orcid.org/0000-0001-8726-3062Bowen Liu − Department of Chemistry and Materials Innovation Factory, University of Liverpool, Liverpool L7 3NY, U.K. Thomas Fellowes − Department of Chemistry and Materials Innovation Factory and Leverhulme Research Centre for Functional Materials Design, University of Liverpool, Liverpool L7 3NY, U.K. Siyuan Yang − Department of Chemistry and Materials Innovation Factory, University of Liverpool, Liverpool L7 3NY, U.K. Alexandra Longcake − Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K.; orcid.org/0000-0003-2881-3938Michael J. Hall − Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K.; orcid.org/0000-0001-6475-9161Michael R. Probert − Chemistry, School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne NE1 7RU, U.K.; orcid.org/0000-0002-2412-7917Yingbo Zhao − School of Physical Science and Technology, ShanhaiTech University, Shanghai 201210, China; orcid.org/0000-0002-6289-7015Complete contact information is available at: https://pubs.acs.org/10.1021/jacs.3c09246 AuthorsQiang Zhu −