Synthesis and structure analysis of chiral enantiomer of 1. Homochiral 1-S and -R were directly synthesized by using commercially available TFP and enantiomerically pure BINAM under solvothermal conditions. The chirality of 1-S and -R is confirmed by circular dichroism (CD) spectra which exhibit nearly perfect mirror images in the range of 230 − 525 nm (Fig. S2). The successful condensation and the purity of product is demonstrated by 1H NMR, 13C NMR spectra (Fig. S3, S4), and mass spectrometry (observed m/z = 2330.6, calculated m/z = 2330.551) for 1-S (Fig. S8). The disappearance of the 1H NMR signal at 12.60 and 12.57 ppm after addition of D2O confirms the presence of an exchangeable NH proton (Fig. S5), suggesting the conversion of imine bond to amine. The keto form was confirmed by 13C NMR spectroscopy (Fig. S4) in which a clear signal near 184 ppm is detected, corresponding to the carbonyl carbons.
Single-crystal X-ray diffraction (SCXRD) analysis reveals that 1-S or -R is a [4 + 6] octahedral molecular cage composed of four TFP and six BINAM crystallizing in F4132 chiral space group (Fig. 1a, 1b and Table S1). In the octahedral cage, TFP occupies four faces and is connected with naphthalene ring through C-N bonds. It is worth noting that one naphthyl of BINAM and TFP are nearly coplanar (dihedral angle: 2.558°). The lengths of C–N and C–C bond ranges from 1.365 to 1.384 Å, which are between the lengths of single (1.47–1.58 Å) and double bond (1.25–1.34 Å), indicating the formation of delocalized conjugated structures (Fig. S9).38 This configuration leads to the dihedral angle of two adjacent planes (73.505°) slightly smaller than binaphthalene diamine monomer (79.254°). The length of C–O bonds on phloroglucinol changes from 1.43 to 1.249 Å illuminating phenolic hydroxyls are rearranged from enols into ketones.37, 39, 42 This rearrangement makes aldehyde group more active than ordinary aromatic aldehydes, which facilitates the condensation reaction towards C–N bond formation. The FTIR spectrum (Fig. S6, S7) of 1-S does not show any characteristic stretching bands of imine (C = N) groups, instead, they present obvious C = C stretching around 1602 cm− 1 and C-N stretching around 1282 cm− 1. These peaks support the formation of keto–enol tautomerism. The estimated volume of the internal cavity is ca. 229.689 Å3, calculating by VOIDOO program with 2.1 Å probe based on the crystal structure (Fig. S10).40 These discrete octahedral cages packing in a window-to-window model generate a 3-D diamondoid porous network (Fig. 1d, 1e).
The porous nature of 1 is probed by N2 adsorption. The measurements at 77 K exhibits a Type I isotherm (Fig. 4a), with a total gas uptake of 205 cm3/g at 1.0 bar and an apparent BET surface area of 343.4 m2/g. Pore size distribution shows a narrow range with a pore-width of 13.9 Å (Fig. S11, S12).
Chiral self-sorting behaviour in cage formation. When using racemic BINAM to react with TFP, only homochiral cages are formed, as confirmed by 1H NMR after reaction using benzene-d6 as solvent and SCXRD signal (Fig. S14 and Fig. 3a, c). The exclusive chiral narcissistic self-sorting is not common in POCs.17, 18, 20 According to Burnside’s lemma, 11 cage isomers (including enantiomers) are possible. Eliminating the enantiomers, the possible cages are six (Fig. 2). In dynamic covalent condensation, the major products are the most thermodynamically stable or those with the lowest Gibbs free energy, in which both enthalpy and entropy have a role. In order to acquire more insight into factors for the favored formation of the homochiral cage, the enthalpy (ΔH) and entropy (ΔS) of all possible isomers were calculated by density functional theory (DFT) calculations (Table S2, Fig. 2). The largest energy difference of ΔS between the homochiral and heterochiral cages is only 15.11 J∙K− 1∙mol− 1 while the energy difference of ΔH reaches 150.35-311.94 kJ mol− 1 and ΔH favors the formation of a homochiral cage over the heterochiral cages. This huge energy difference leads to ΔG of homochiral cage lower than that of heterochiral ones by 102.25-316.44 kJ mol− 1. These results illuminate homochiral cage is the thermodynamically stable conformation and the exclusive chiral narcissistic self-sorting is enthalpy-driven process.
Chiral self-sorting on supramolecular level. The supramolecular assembly of 1-S and 1-R cages exhibits controllable chiral self-discrimination and self-recognition via precisely adjusting organic solvents. When the solvent is mesitylene, the racemic structure (1-R/S) is obtained (Fig. 3e). SCXRD analysis shows 1-R/S crystallizes in P-1 space group, two enantiomer cages are stacked in wall-to-wall manners (Fig. S15), and the cavities and intermolecular space are occupied by mesitylenes. The purity of the sample is illuminated by PXRD (Fig. S16). When mesitylene is replaced with benzene or toluene, homochiral crystals without guests are obtained (Fig. 3a, c), and the structure is the same as that prepared from the enantiomerically pure precursor.
Interestingly, the homochiral and racemic crystallization presents supramolecular structural reversible transformations (Fig. 4). When equimolar crystals of 1-S and 1-R were dissolved in mesitylene and heated at 120°C for 3.5 days, the crystals of 1-R/S⊃mesitylene were obtained as confirmed by SCXRD and PXRD (Fig. S17). The obtained heterochiral crystals can return to homochiral crystallization in toluene under similar conditions (Fig. S17). While it has been previously reported the transformation of the crystal of homochiral cage to racemic 1-R/S structure,16–19 this is the first time, the controllable reversible transformation between the single crystal of homochiral and racemic structure is achieved.
DFT calculations are carried out to clarify the mechanism of solvent-controlled chiral self-sorting. Based on reduced density gradient (RDG) analysis, the intuitive information about molecular interactions for homochiral cage and racemic structure are shown in Fig. 3g and S18, S19.41 If the neighboring cages are heterochiral, the interaction energy of the structure is only − 8.0 kcal/mol and the intermolecular distance is increased comparing with homochiral configuration. As a comparison, the interaction energy of the homochiral cage is decreased to -24.83 kcal/mol for strong π–π interactions between adjacent cages, which means the homochiral packing is more stable and preferred. When mesitylene is introduced into racemic system, the lower interaction energy of -62 kcal/mol is obtained benefiting from the π–π and C–H…π interactions between mesitylenes and cages. When the mesitylene is changed to benzene or toluene, the interaction energy is increased to -29.93 kcal/mol which is close to homochiral configuration. These conclusions well verify the experimental results and clarify intermolecular forces play an important role in cage chiral self-sorting. Besides, we find only two methyl groups at an angle of 120° can undertake the C–H…π interaction between neighboring cages while the left methyl plays a space-occupying role (Fig. S18). In order to verify the results of a theoretical calculation, three different solvents, including p-xylene, m-xylene and 5-iodo-m-xylene, were used. 1-R/S crystal is obtained only in 5-iodo-m-xylene, and the arrangement of 5-iodo-m-xylene in the structure is similar to mesitylene (Fig. S20). Calculated interaction energy (-67.08 kcal/mol) is also similar to the case of mesitylene (-62 kcal/mol). Combining the results of theoretical calculations and experiments, the chiral self-sorting of cage can be precisely regulated through solvent and supramolecular interactions.
Stability of 1- S. Chemical stability is one of the knotty issues that plague the development of chiral POCs.37 The chemical stability of homochiral 1-S is investigated under various harsh conditions including boiling water, and concentrated base and acid (12 M NaOH, 1 M HCl and H2SO4). Excitingly, 1-S presents outstanding stability toward water and also to both concentrated acids and bases. As confirmed by FTIR and 1H NMR (Fig. S21, S22,), there is not any chemical decomposition of 1-S when it was soaked in boiling water, NaOH (12 M), HCl (1 M) and H2SO4 for 7 days. From the intact powder X-ray diffraction (PXRD, Fig. 5a) pattern and the crystal photographs (Fig. S23), we can find there is no loss of crystallinity, as well. Likewise, these treatments of concentrated acidic and basic solutions do not affect the porosity in 1-S, as witnessed by the N2 adsorption isotherms after treatment (Fig. 5b). The chemical stability of this POC towards both alkaline and acid solutions outperforms the reported POCs (Table S4). We believe the high durability of 1-S to the extremely harsh conditions not only ascribes to the keto-enamine structure, but also benefits from the aromatic skeleton which facilitates electron delocalization and provides the steric hindrance and hydrophobicity around the amine bond preventing its hydrolysis. The high hydrophobicity of the crystal surface is verified by the water contact angle of 145.7° (Fig. S24).
In thermal stability, 1-S also has appealing performance. Through thermogravimetric analysis (Fig. S25), it is found there is a weight loss of about 8% before 90°C, which can be attributed to the loss of solvent molecules. Then, a platform appeared before 200°C, indicating the structure can be stabilized to this temperature. In order to further prove its thermal stability, a variable temperature PXRD test was carried out with an interval of 50°C (Fig. S26). No obvious change is observed, indicated 1-S can be stable before 200°C.
Enantioselective recognition of biaryl molecules. As crucial components in the biological system, the enantiomer recognition of atropisomerically biaryl molecules is of significant importance to life sciences and pharmaceutics.43, 44 The observed supramolecular interactions may endow 1 capacity for enantioselective recognition of biaryl molecules.45 Therefore, 1 is selected as a sensor for six enantiomers B1-B6. Chiral sensing experiments were conducted by immersing activated enantiopure 1 into the solution of analytes separately and evaluated by the fluorescence of analytes. To get a clear evaluation, the changes (ΔI) in luminescence intensity before and after adding 1 is normalized (ΔI/I0). As shown in Fig. 6, S27, 1-S preferred S-fashion substrates over the R-fashion, especially to B4 with the selectivity up to 98%. Recycle experiments show the sensing ability maintains by ~ 85% after five rounds of recycling. (Fig. S28). The limit of detection (LOD) of 1-S to S-B4 was determined to be 0.597 µM (Fig. S29, S30). A similar selectivity also occurs in 1-R to R-fashion substrates. These results demonstrate 1 could be a promising probe for recognition of enantiomer atropisomerically biaryl molecules. To clarify the internal reasons for the recognition process, molecular dynamics simulation and DFT calculations on 1-S to R-B4 and S-B4 were carried out. Comparing with 1-S/R-B4, 1-S/S-B4 has much stronger interaction energy by 16.13 kcal/mol (Fig. S31, S32 and Table S5). Moreover, larger electronic coupling for excitation energy transfer of 1-S/S-B4 than that of 1-S/R-B4 is also found (Table S5). These results suggest stronger interaction and more efficient energy transfer between 1-S and S-B4 may result in the observed larger changes (ΔI) in luminescence intensity.