Tetraphenylethene-Embedded Pillar[5]arene and [15]Paracyclophane: Distorted Cavities and Host–Guest Binding Properties

Two aggregation-induced emission (AIE) macrocycles (DMP[5]-TPE and PCP[5]-TPE) were prepared by embedding Tetraphenylethene (TPE) unit into the skeletons of Dimethoxypillar[5]arene (DMP[5]) and [15]Paracyclophane ([15]PCP) at meso position, respectively. In crystal, the PCP[5]-TPE showed a distorted cavity, and the incubation of hexane inside the DMP[5]-TPE cavity caused a distinct change in the molecular conformation compared to PCP[5]-TPE. There was no complexation between PCP[5]-TPE and 1,4-dicyanobutane (DCB). UV absorption experiments showed the distorted cavity of DMP[5]-TPE hindered association with DCB.


Introduction
Macrocyclic molecules are the most important supramolecular hosts, with multivalent binding sites and ring-like structures [1]. Pillararenes are new generation macrocyclic molecules, made up of hydroquinone units linked by methylene bridges [2][3][4][5]. The structures of pillararenes are similar to that of calixarenes, but are much more symmetrical [1]. Pillararenes show excellent host-guest binding properties, which can not only recognize ionic guests [6,7], but also interact strongly with selective neutral objects [8,9]. [15]Paracyclophane ( [15]PCP) received a great deal of attention since the first report by Huang in 2018 [10]. [15]PCP is a new carbon-bridged macrocycle, and its structure is similar to that of pillar [5]arene. [15]PCP can be synthesized by the hydrodeoxygenation of pillar [5]arene via aryl fluorosulfonate intermediates with a high yield.
There are several potential modification positions in pillararene, such as rims [4,[11][12][13][14], meta, and bridging meso positions [15]. Current explorations of function pillararene still focus on the meta or rim positions. However, the functionalization of pillararene at the meso position has not been as extensively explored as that of their meta or rim positions. Meanwhile, due to the absence of the alkoxy groups, there are fewer modification sites than pillararenes, so the modification of the meso position of [15]PCP is particularly important [16]. Unlike the rim positions, the modifications at the meso positions may distort the cavity of the pillararene, which depends on the structure of the introduced substituents [15,17]. Meanwhile, a distorted cavity may exhibit different host-guest binding properties. Therefore, it is important to explore the host-guest binding properties of the meso position of pillararene.
Tetraphenylethylene (TPE) is an aggregation-induced emission (AIE) molecule that has been extensively studied. The TPE skeleton owns propeller-like conformation with one double-bond stator and four phenyl rotors [18][19][20][21][22]. The TPE unit can be embedded into the skeletons of pillararenes by a few reactions. To maintain the lower-energy state of the TPE unit, the skeletons of pillararene are deformed to keep their propeller-like conformation [15].
As shown in Scheme 1, DMP [5] the meso position anion was generated by deprotonation of DMP [5] with 5.0 eqiv. of n-butyllithium. Then, the DMP [5] anion proceeded to the nucleophilic addition reaction with 6.0 equiv. of benzophenone, which was followed by dehydration using p-toluenesulphonic acid as a catalyst in the refluxing toluene, resulting in DMP[5]-TPE with an overall yield of 6.7% (Figures S1-S4). The synthesis of PCP[5]-TPE was carried out in the same way as for the synthesis of DMP[5]-TPE, but [15]PCP was used instead of DMP [5], and 4,4'-dimethoxybenzophenone instead of benzophenone, resulting in PCP[5]-TPE with an overall yield of 95% ( Figures S5-S8). Unexpectedly, under the same experimental procedures, the yield of DMP[5]-TPE was much lower than PCP[5]-TPE. Two main reasons may account for this significant difference: (1) In common solvents for lithiation reactions, DMP [5] is only slightly more soluble in THF, and so a large amount of undissolved DMP [5] could not participate efficiently in the lithiation reaction. Contrarily, [15]PCP has good solubility in THF. (2) The structure of DMP [5] contains ten methoxy groups, and these electron-donating groups could increase the electron density of the meso position and decrease the lithiation reaction yield. The identities of the above-mentioned products were all unequivocally confirmed by NMR spectroscopy and high-resolution mass spectroscopy.
Molecules 2020, 25, x FOR PEER REVIEW 2 of 8 of the TPE unit, the skeletons of pillararene are deformed to keep their propeller-like conformation [15]. In this research, we report two macrocycles (DMP [5]-TPE and PCP [5]-TPE) prepared by embedding the TPE unit into the meso position of the skeletons of Dimethoxypillar [5]arene (DMP [5]) and [15]PCP, respectively.
As shown in Scheme 1, DMP [5] the meso position anion was generated by deprotonation of DMP [5] with 5.0 eqiv. of n-butyllithium. Then, the DMP [5] anion proceeded to the nucleophilic addition reaction with 6.0 equiv. of benzophenone, which was followed by dehydration using p-toluenesulphonic acid as a catalyst in the refluxing toluene, resulting in DMP [5]-TPE with an overall yield of 6.7% (Figures S1-S4). The synthesis of PCP [5]-TPE was carried out in the same way as for the synthesis of DMP[5]-TPE, but [15]PCP was used instead of DMP [5], and 4,4'-dimethoxybenzophenone instead of benzophenone, resulting in PCP [5]-TPE with an overall yield of 95% ( Figures S5-S8). Unexpectedly, under the same experimental procedures, the yield of DMP[5]-TPE was much lower than PCP[5]-TPE. Two main reasons may account for this significant difference: (1) In common solvents for lithiation reactions, DMP [5] is only slightly more soluble in THF, and so a large amount of undissolved DMP [5] could not participate efficiently in the lithiation reaction. Contrarily, [15]PCP has good solubility in THF. (2) The structure of DMP [5] contains ten methoxy groups, and these electron-donating groups could increase the electron density of the meso position and decrease the lithiation reaction yield. The identities of the above-mentioned products were all unequivocally confirmed by NMR spectroscopy and high-resolution mass spectroscopy. Take the 1 H NMR of DMP[5]-TPE as an example ( Figure S1). The resonance at δ= 7.02 ppm as a single peak was assigned to the phenyl protons of the TPE unit outside the skeleton of pillar [5]arene. The resonance peaks of Δ = 6.72, 6.66, 6.65, 6.36 and 6.18 ppm were assigned to the phenyl protons of the pillar [5]arene, the δ = 3.81 and 3.72 resonance peaks were assigned to the remaining meso protons, and the δ = 3.66, 3.61, 3.54, 3.38, and 2.65 ppm resonance peaks were assigned to the methoxy groups protons. Remarkably, the resonance of the six protons of the methoxy groups at δ = 2.65 ppm as a single peak showed a high-field shift, which indicated that the two methoxy groups rotated in the cavity of the pillar [5]arene due to the propeller-like conformation of the TPE unit.
Fortunately, the crystal of DMP [5]-TPE and PCP[5]-TPE was obtained by slowly evaporating the mixed solutions of dichloromethane and petroleumether. As shown in Figure 1, the TPE unit was embedded in the skeletons of the pillararenes successfully. With no complexation with the guest, the pillar scaffold of PCP [5]-TPE adopts an exceedingly distorted conformation (Figures 1a and S9). The dihedral angles between the phenyl moieties of the TPE unit and the ethylene plane are 37.98°, 47.2°, 52.31°, and 62.13°, respectively. In contrast, due to the complexation with hexane, DMP [5]-TPE shows an almost symmetrical cavity identical to that of DMP [5] (Figures 1b and S11). The dihedral angles between the phenyl groups and the planes constructed by the five-pillar meso carbons are 44.21°, 74.04°, 87.40°, and 87.75°, respectively. These results indicate that the combination of host-guest will induce a significant change in the molecular conformation. Take the 1 H NMR of DMP[5]-TPE as an example ( Figure S1). The resonance at δ = 7.02 ppm as a single peak was assigned to the phenyl protons of the TPE unit outside the skeleton of pillar [5]arene. The resonance peaks of ∆ = 6.72, 6.66, 6.65, 6.36 and 6.18 ppm were assigned to the phenyl protons of the pillar [5]arene, the δ = 3.81 and 3.72 resonance peaks were assigned to the remaining meso protons, and the δ = 3.66, 3.61, 3.54, 3.38, and 2.65 ppm resonance peaks were assigned to the methoxy groups protons. Remarkably, the resonance of the six protons of the methoxy groups at δ = 2.65 ppm as a single peak showed a high-field shift, which indicated that the two methoxy groups rotated in the cavity of the pillar [5]arene due to the propeller-like conformation of the TPE unit.
Fortunately, the crystal of DMP[5]-TPE and PCP[5]-TPE was obtained by slowly evaporating the mixed solutions of dichloromethane and petroleumether. As shown in Figure 1, the TPE unit was embedded in the skeletons of the pillararenes successfully. With no complexation with the guest, the pillar scaffold of PCP[5]-TPE adopts an exceedingly distorted conformation ( Figure 1a and Figure S9). The dihedral angles between the phenyl moieties of the TPE unit and the ethylene plane are 37.98 • , 47.2 • , 52.31 • , and 62.13 • , respectively. In contrast, due to the complexation with hexane, DMP[5]-TPE shows an almost symmetrical cavity identical to that of DMP [5] (Figure 1b and Figure S11). The dihedral angles between the phenyl groups and the planes constructed by the five-pillar meso carbons are 44.21 • , 74.04 • , 87.40 • , and 87.75 • , respectively. These results indicate that the combination of host-guest will induce a significant change in the molecular conformation.
the molecules more tightly connected and further restrict the intramolecular movement of the TPE units, leading to the intense fluorescence in the polymerized state. Further measurements of the molecular arrangements revealed the intermolecular ArH-interaction with a minimum contact distance of 3.206 Å. The same study for DMP [5]-TPE showed that DMP [5]-TPE crystalized in an orthorhombic Pbca space group, and that there was an intermolecular ArH-interaction with a minimum contact distance of 3.058 Å (Figures 1d and S12). Therefore, DMP [5]-TPE is packed more tightly than PCP[5]-TPE.

PCP[5]
-TPE crystalizes in a monoclinic P2 1 /n space group. Short ArH-contacts exist between the adjacent TPE units (Figure 1c and Figure S10). These intermolecular contacts make the molecules more tightly connected and further restrict the intramolecular movement of the TPE units, leading to the intense fluorescence in the polymerized state. Further measurements of the molecular arrangements revealed the intermolecular ArH-interaction with a minimum contact distance of 3.206 Å. The same study for DMP [5]-TPE showed that DMP[5]-TPE crystalized in an orthorhombic Pbca space group, and that there was an intermolecular ArH-interaction with a minimum contact distance of 3.058 Å (Figure 1d and Figure  However, when f w increased to over 80%, the fluorescence intensity significantly increased (Figure 2a,b, Figures S13 and S14). Meanwhile, the PCP[5]-TPE solution in the THF-H 2 O mixture displayed a significant enhancement in fluorescence when f w exceeded 90% (Figure 2c,d, Figures S15 and S16). In addition, in terms of the fluorescence wavelength, with the f w increasing from 90% to 99%, the aggregation-induced fluorescence of DMP[5]-TPE showed a 12 nm blue shift from 460.2 nm to 448.2 nm. At the same time, PCP[5]-TPE showed a 3.4 nm blue shift from 475 nm to 471.6 nm. In the same experiments for free TPE, a remarkable fluorescence enhancement was observed when f w increased to 95% (Figure 2e,f, Figures S17 and S18). The f w increase from 95% to 99% was accompanied by a blue shift in the emission wavelength of 1.  Subsequently, the binding properties of DMP [5]-TPE and PCP [5]-TPE were first performed by 1 H NMR (Figures 3, 4, S19 and S20). As the guest for the host-guest interaction research, 1,4-dicyanobutane (DCB) was selected. As shown in Figure 3, The 1 H NMR spectra of the solution of DMP [5]-TPE in CDCl3 in the absence and presence of the DCB guest were recorded. For the complex, on the NMR timescale, a slow exchange was observed. The resonances of the new species are consistent with the formation of an interpenetrated complex. In the presence of 1.0 equivalent DCB, the five resonance peaks of the phenyl protons of the pillar [5]arene skeleton were merged into a slope-shaped resonance peak  Figure S19 and S20). As the guest for the hostguest interaction research, 1,4-dicyanobutane (DCB) was selected. As shown in Figure 3, The 1 H NMR spectra of the solution of DMP[5]-TPE in CDCl 3 in the absence and presence of the DCB guest were recorded. For the complex, on the NMR timescale, a slow exchange was observed. The resonances of the new species are consistent with the formation of an interpenetrated complex. In the presence of 1.0 equivalent DCB, the five resonance peaks of the phenyl protons of the pillar [5]arene skeleton were merged into a slope-shaped resonance peak accompanied by a minor low-field shift. At the same time, the resonance assigned to phenyl protons of the TPE unit outside the skeleton of pillar [5]arene were shown as multiplet peaks. The remaining meso protons and methoxy groups protons of the pillararene showed a double peak signal. Especially, the disappearance of the signal of the methoxy groups at δ = 2.65 ppm suggested that the distortion of the cavity of DMP  Unexpectedly, for the PCP[5]-TPE, as shown in Figure 4, even with the addition of two equivalents of DCB, the peaks of PCP[5]-TPE and DCB showed no observable shifts or broadening. This phenomenon indicated that no complexation, or weak complexation between PCP[5]-TPE and DCB, could be attributed to the absence of the methoxy groups in the [15]PCP structure because the dipole-dipole interaction between the methoxy groups and DCB played a leading role in the host-guest binding [1,23]. Unexpectedly, for the PCP[5]-TPE, as shown in Figure 4, even with the addition of two equivalents of DCB, the peaks of PCP[5]-TPE and DCB showed no observable shifts or broadening. This phenomenon indicated that no complexation, or weak complexation between PCP[5]-TPE and DCB, could be attributed to the absence of the methoxy groups in the [15]PCP structure because the dipole-dipole interaction between the methoxy groups and DCB played a leading role in the host-guest binding [1,23].
The stoichiometry of complexation between DMP[5]-TPE and DCB was further investigated by Job's plot method based on the UV-vis absorption experiments ( Figure S21 Figure S23). In order to investigate the changes of the host-guest binding properties of the meso position of pillararene, DMP [5] was also tested in the same manner. The association constant (K a ) of DCB ⊂ DMP [5] was determined to be (2.14 ± 0.08) × 10 4 M −1 ( Figure S24). The association constants for DCB ⊂ DMP[5]-TPE and DCB ⊂ DMP [5] were both in the vicinity of 10 4 M −1 in CHCl 3 , and DCB ⊂ DMP[5]-TPE was slightly lower. The 1 H NMR spectra of the solution of DMP[5]-TPE in CDCl 3 in the presence of the DCB guest showed the re-symmetry of the cavity of DMP[5]-TPE. Thus, DCB was required to overcome the hindrances of the distorted cavity during the host-guest binding process. This could possibly be the reason for the decreased association constant for DMP [5]-TPE compared to the DMP [5] (Table S1).
Molecules 2020, 25, x FOR PEER REVIEW 6 of 8  Figure S23). In order to investigate the changes of the host-guest binding properties of the meso position of pillararene, DMP [5] was also tested in the same manner. The association constant (Ka) of DCB ⊂ DMP [5] was determined to be (2.14 ± 0.08) × 10 4 M −1 ( Figure S24). The association constants for DCB ⊂ DMP [5]-TPE and DCB ⊂ DMP [5] were both in the vicinity of 10 4 M −1 in CHCl3, and DCB ⊂ DMP[5]-TPE was slightly lower. The 1 H NMR spectra of the solution of DMP [5]-TPE in CDCl3 in the presence of the DCB guest showed the re-symmetry of the cavity of DMP[5]-TPE. Thus, DCB was required to overcome the hindrances of the distorted cavity during the host-guest binding process. This could possibly be the reason for the decreased association constant for DMP [5]-TPE compared to the DMP [5] (Table.  S1).