Sequence Engineering in Tuning the Circularly Polarized Luminescence of Aggregation-Induced Emission-Active Hetero3rotaxanes

Open AccessCCS ChemistryRESEARCH ARTICLES21 Feb 2024Sequence Engineering in Tuning the Circularly Polarized Luminescence of Aggregation-Induced Emission-Active Hetero3rotaxanes Zhiyong Peng, Pei-Pei Jia, Xu-Qing Wang, Xiao-Li Zhao, Hai-Bo Yang and Wei Wang Zhiyong Peng Shanghai Key Laboratory of Green Chemistry and Chemical Processes, State Key Laboratory of Petroleum Molecular 4.7 g, 5.0 mmol). The Schlenk flask was then evacuated and backfilled with N2 three times. Next, 10 mL of the freshly distilled CHCl3 was added via syringe. The resultant solution was stirred for 1 h under −15 °C. Then the mixture of pentafluorophenol (0.81 g, 4.4 mmol) and Et3N (0.53 g, 5.0 mmol) in 3 mL freshly distilled CHCl3 was added to the solution under an inert atmosphere, and the reaction mixture was allowed to warm to room temperature and stirred overnight. The solution was concentrated and the residue was purified by column chromatography (SiO2; petroleum ether (PE)/dichloromethane (DCM) = 4:1, v/v) to obtain the white solid 1.8 g with the yield of 72%. In addition, an optimized column-free purification procedure has been also developed. After evaporation of the solvent the crude material was then dissolved in a minimum amount of CH2Cl2 and poured into n-hexane to precipitate DEP5A. The resultant filtrate was collected, concentrated and followed by dissolving in a minimum amount of CH2Cl2 again and poured into acetonitrile to precipitate target 2rotaxane 1 with the yield of 66% on a multigram scale. 1H NMR (CDCl3, 300 MHz): δ = 6.92 (s, 10 H), 4.04–3.79 (m, 20 H), 3.76 (s, 10 H), 2.20–2.15 (m, 4 H), 1.46–1.24 (m, 38 H), 0.69–0.59 (m, 4 H), −0.91 (brs, 4 H), −1.42 (brs, 4 H); 19F NMR (CDCl3, 282 MHz): δ = −153.59, −157.95, −162.64; 13C NMR (125 MHz, CDCl3, 298 K): δ = 170.00, 149.81, 128.59, 114.43, 63.69, 33.13, 31.59, 30.36, 29.32, 27.75, 27.60, 24.94, 15.47, 1.17, 0.14; high-resolution electron spray ionization mass spectroscopy (HR ESI-MS): calcd for C77H86F10O14+, 1424.5858; found, 1424.5858. General protocol for wheel-assembling process To a stirred solution of key 2rotaxane precursor 1 (1.0 equiv) in tetrahydrofuran (THF) were added benzylamine derivative (1.0 equiv). The reaction mixture was stirred for 48 h at room temperature. The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography (SiO2, PE/DCM = 1:1, v/v). The resultant intermediate (1.0 equiv) was dissolved in Tol./DCM with benzylamine derivative (1.0 equiv) and crown ether (6.0 equiv). The reaction mixture was stirred at room temperature for 48 h. The solvent was removed under reduced pressure and the residue was purified by preparative thin layer chromatography (SiO2, DCM/ethyl acetate (EA) = 8:1, v/v). Results and Discussion In our study, inspired by recent developments in postsynthetic modification of rotaxanes,72–77 a wheel-assembling approach was proposed for the efficient, precise, and diverse synthesis of both sequence isomers of hetero3rotaxanes. First, to shorten the synthetic routes and improve the synthetic efficiency, a 2rotaxane with exchangeable stoppers was employed as the key precursor. Along with the stopper-exchange reaction that introduced specific functional groups as new stoppers, additional wheel components were also introduced through a metal-free active template strategy,67,78–80 thus leading to the evolution from the initial 2rotaxane to corresponding 3rotaxanes. Starting from the 2rotaxane with the same two exchangeable stoppers, by controlling the sequence of the stopper-exchange reactions, both the functional groups and wheel components were facilely assembled from either side, thus resulting in the precise synthesis of both sequence isomers of hetero3rotaxanes in a controllable divergent way. More importantly, if a chiral 2rotaxane with a chiral wheel was employed as the starting precursor, the corresponding functional chiral 3rotaxanes could be obtained since both the stopper exchange and wheel-assembling process would not lead to the dethreading of the original wheel component, thus resulting in the chirality retention of the hetero3rotaxanes. With such a design strategy in mind, in this study, we introduced pentafluorophenyl ester moieties81–83 as exchangeable stoppers. On the one hand, the existence of pentafluorophenyl ester stoppers could promote the facile structural analysis of the key intermediates with fluorine NMR spectra. On the other hand, the pentafluorophenyl ester stoppers significantly enhanced the solubility of 2rotaxane precursor that enabled the chiral resolution on a large scale, thus further making the investigations on the chirality retention in the wheel-assembling process feasible. In addition, considering the unique planar chirality of pillar5arene,84–89 its host–guest complex with neutral alkyl chain was employed as the rotaxane moiety for the synthesis of chiral rotaxanes.90,91 The reaction of sebacoyl chloride with pentafluorophenol in the presence of an excess of DEP5A and Et3N in CHCl3 afforded the desired 2rotaxane precursor 1 (Figure 2 and Supporting Information Scheme S1). A small amount of the corresponding axle component byproduct was also generated from the reaction of uncomplexed sebacoyl chloride with pentafluorophenol. The 2rotaxane 1 was prepared and conveniently separated by silica gel column chromatography in several grams scale with a yield of 72%. More importantly, an optimized column-free purification procedure has also been developed. After confirming the completion of the reaction through thin-layer chromatography monitoring and evaporation of the solvent, the crude material was then dissolved in a minimum amount of CH2Cl2 and poured into n-hexane to precipitate DEP5A. The resultant filtrate was collected, concentrated, and followed by dissolving it in a minimum amount of CH2Cl2 again and poured into acetonitrile to precipitate target 2rotaxane 1 with the yield of 66% on a multigram scale. Figure 2 | The synthetic route and single-crystal X-ray structures of both enantiomers of 2rotaxanes 1 as the key precursor for the synthesis of sequence isomers of hetero3rotaxanes. Download figure Download PowerPoint 2rotaxane 1 is highly soluble in common solvents and perfectly stable under normal laboratory conditions for several months, which not only makes the resolution of the enantiomers feasible but also lays the foundation for the further synthesis of hetero3rotaxanes. The optical resolution of 1 was successfully carried out by preparative chiral stationary phase-high performance liquid chromatography (CSP-HPLC), and the absolute configurations of 2rotaxane 1 in the first fraction and the second fraction were assigned to be Rp and Sp according to their single crystal X-ray structures, respectively (Figure 2, Supporting Information Figures S1–S5, S41, S42, S54–S61, and Table S2). Notably, both enantiomers were easily resolved on the scale of several hundreds of milligrams, which were sufficient for the synthesis of corresponding chiral hetero3rotaxanes, particularly the AIEgen-functionalized ones. With the key 2rotaxane precursor 1 in hand, the further synthesis of sequence isomers of corresponding hetero3rotaxanes were then carried out. In our study, additional crown ether wheel components were further assembled from either side of the initial 2rotaxane through metal-free active template strategy along with the stopper exchange process ( Supporting Information Scheme S2).67,78,79 Thus from the same 2rotaxane precursor 1, when one additional crown ether wheel and two different stoppers are introduced, there will be two sequence isomers. In order to firstly confirm the feasibility of newly-developed wheel-assembling approach, 3,5-bis(trifluoromethyl)benzylamine and 3,5-dibromobenzylamine ( Supporting Information Scheme S3 and Figure S53) were selected as two different stoppers. As shown in Figure 3a, treatment of 2rotaxane 1 with equimolar 3,5-bis(trifluoromethyl)benzylamine at room temperature for 48 h in THF afforded monosubstituted 2rotaxane 2 with a yield of 67%. By further employing the metal-free active template approach, the reaction of monosubstituted 2rotaxane 2, 3,5-dibromobenzylamine and dibenzo-24-crown-8 ( DB24C8) in a ratio of 1:2:6 in toluene/DCM (v/v, 1:1) resulted in the successful preparation of one sequence isomer, hetero3rotaxane HR-S1, in 43% yield ( Supporting Information Scheme S3). To obtain the other sequence isomer HR-S2, 3,5-dibromobenzylamine was first introduced as stopper to afford the monosubstituted 2rotaxane 3 through the stopper-exchange reaction in 60% yield. The sequential stopper-exchange reaction with 3,5-bis(trifluoromethyl)benzylamine in the presence of DB24C8 resulted in the successful synthesis of HR-S2 in 80% yield. Notably, for both sequence isomers, the DB24C8 wheel was also introduced in the first stopper-exchange process, resulting in the corresponding hetero3rotaxane intermediates 4 and 5 in 21% and 59% yields, respectively. Notably, the chemical structures of these two key intermediates were unambiguously confirmed by single-crystal X-ray analysis (Figure 3c and Supporting Information Figures S43 and S44). The further stopper-exchange reaction would then led to the successful synthesis of targeted sequence isomers in 85% and 84% yields, respectively. Figure 3 | (a) The wheel-assembling approach for the precise synthesis of both sequence isomers of hetero3rotaxanes HR-S1 and HR-S2. Reaction conditions: (i) 3,5-bis(trifluoromethyl)benzylamine (1.0 equiv), THF, rt., 48 h, 67%; (ii) 3,5-dibromobenzylamine (2.0 equiv), DB24C8 (6.0 equiv), Tol./DCM, rt., 48 h, 43%; (iii) 3,5-dibromobenzylamine (1.0 equiv), THF, rt., 48 h, 60%; (iv) 3,5-bis(trifluoromethyl)benzylamine (2.0 equiv), DB24C8 (6.0 equiv), Tol./DCM, rt., 48 h, 80%; (v) 3,5-dibromobenzylamine (1.0 equiv), DB24C8 (6.0 equiv), Tol./DCM, rt., 48 h, 21%; (vi) 3,5-bis(trifluoromethyl)benzylamine (4.0 equiv), THF, reflux, 48 h, 85%; (vii) 3,5-bis(trifluoromethyl)benzylamine (1.0 equiv), DB24C8 (6.0 equiv), Tol./DCM, rt., 48 h, 59%. (viii) 3,5-dibromobenzylamine (4.0 equiv), THF, reflux, 48 h, 84%. (b) The 1H NMR spectra (CDCl3, 298 K, 500 MHz) of HR-S1 and HR-S2. (c) Single-crystal X-ray structures of the key intermediates 4, 5, and the resultant hetero3rotaxane sequence isomers HR-S1 and HR-S2 (only the Rp isomers are shown) Download figure Download PowerPoint The resultant sequence isomers described above were fully characterized using 1-D multinuclear (1H, 13C, and 19F), 2-D rotating frame overhauser effect spectroscopy (ROESY) techniques, HR ESI-MS, and unambiguous single-crystal X-ray analysis ( Supporting Information Figures S62–S91 and Tables S3–S5). As revealed by 1H NMR spectra (Figure 3b, Supporting Information Figures S82 and S87), for the sequence isomers of both HR-S1 and HR-S2, attributed to the varied shielding effects of wheels in different sequences, remarkable differences in chemical shifts were observed. For instance, for HR-S1, due to the strong shielding effect of DEP5A, the highest upfield chemical shifts of ca. −2.18 ppm were observed for H3 in the alkyl chain, while the same case was found for H6 for HR-S2. Such obvious differences were reasonable since these two protons were proven to be located in the middle cavity of DEP5A of each sequence by single-crystal X-ray structures (Figure 3c and Supporting Information Figures S45 and S46). According to the above-discussed results, by simply combining different stoppers and wheels as well as programming the synthetic sequences, the synthesis of both sequence isomers of diverse hetero3rotaxanes was confirmed to be precisely controllable, thus laying the foundation for further explorations of their unique properties such as the AIE and CPL behavior. After confirming the successful development of the wheel-assembling approach for the synthesis of both sequence isomers of hetero3rotaxanes, the further synthesis of the sequence isomers of AIE-active hetero3rotaxanes was then carried out. In our study, the typical AIEgen tetraphenylethene (TPE) was selected as the functional stopper.42,92–95 Notably, since we have a sufficient amount of chiral 2rotaxane precursors Rp- 1 and Sp- 1, they were directly used for the synthesis of sequence isomers of chiral AIEgen-functionalized hetero3rotaxanes. However, when synthesizing the targeted sequence isomers with DB24C8, the one with the DB24C8 wheel close to the TPE stopper could not be achieved, possibly because the weaker N–H···O hydrogen bond could not overcome the steric hindrance and so was unable to assemble the DB24C8 wheel, only leading to the synthesis of corresponding 2rotaxane TPE-2R ( Supporting Information Scheme S4 and Figures S116–S119). In this case, considering the possible steric hindrance effect, a 24-crown-8 ( 24C8) was then employed as the wheel component instead.80 To our delight, this more flexible wheel with less steric hindrance could be successfully assembled, thus leading to the successful synthesis of both the sequence isomers TPE-S1 and TPE-S2 of functional hetero3rotaxanes through the key intermediates 2 and 6, respectively (Figure 4a, Supporting Information Scheme S5, and Figures S92–S115). Figure 4 | (a) The wheel-assembling approach for the synthesis of both sequence isomers of AIEgen-functionalized hetero3rotaxanes TPE-S1 and TPE-S2, and their single-crystal X-ray structures (only the Sp isomers are shown). Reaction conditions: (i) 3,5-bis(trifluoromethyl)benzylamine (1.0 equiv), THF, rt., 48 h, 67%; (ii) TPE-NH2 (1.0 equiv), THF, rt., 48 h, 50%; (iii) TPE-NH2 (2.0 equiv), 24C8 (6.0 equiv). Tol., 0 °C, 48 h, 10%; (iv) 3,5-bis(trifluoromethyl)benzylamine (2.0 equiv), 24C8 (6.0 equiv). Tol., rt., 48 h, 80%; (b) Chirality retention in the wheel-assembling approach. Chiral HPLC traces (n-Hex:EA = 96:4, v/v) of rac-1, Rp-1 (the first fraction of rac-1), and Sp-1 (the second fraction of rac-1) (left). Chiral HPLC traces (n-Hex:EA = 88:12, v/v) of rac-6, Rp-6 (synthesized from Rp-1) and Sp-6 (synthesized from Sp-1) (middle). Chiral HPLC traces (n-Hex:EA = 75:25, v/v) of rac-TPE-S2, Rp-TPE-S2 (synthesized from Rp-6) and Sp-TPE-S2 (synthesized from Sp-6) (right). Download figure Download PowerPoint Notably, upon the synthesis of these chiral hetero3rotaxanes sequence isomers, both the simple stopper-exchange and associated wheel-assembling process would not allow the dethreading of the DEP5A wheel since the key reaction intermediates could be regarded as even "bigger" stoppers ( Supporting Information Scheme S2). Thus, the direct employment of chiral 2rotaxane Rp- and Sp- 1 as starting materials led to the synthesis of corresponding sequence isomers of chiral AIEgen-functionalized hetero3rotaxanes through the chirality retention process (Figure 4b, Supporting Information Schemes S6, S7, and Figures S6–S22). As revealed by the chiral HPLC traces, starting from Rp- 1 (99.4:0.6 e.r.) and Sp- 1 (99.5:0.5 e.r.), the successful synthesis of corresponding chiral 2rotaxane intermediates Rp- 6 and Sp- 6 were realized with e. r. values of 99.5:0.5 and 99.7:0.3, respectively ( Supporting Information Figures S23–S27). Moreover, starting from these chiral intermediates Rp- 6 and Sp- 6, the further stopper-exchange reaction resulted in the successful synthesis of Rp- TPE-S2 and Sp- TPE-S2 with no degradation of e.r. values ( Supporting Information Figures S28–S32), and the chirality of the targeted AIEgen-functionalized hetero3rotaxanes were confirmed by single-crystal X-ray structures ( Supporting Information Figures S47–S52 and Tables S6, S7), demonstrating chirality retention during the whole synthetic routes. Having both sequence isomers of AIE-active hetero3rotaxanes in hand, their sequence-dependent AIE behavior and CPL performance were then investigated. For these two sequence isomers, the key difference is the arrangements of chiral wheel and AIEgen stopper along the axle components. The different structural features of pillar5arene and crown ether (rigid vs flexible and chiral vs achiral) would have great impact in the property engineering of the resultant isomers, thus the sequence-dependent AIE behavior of TPE-S1 and TPE-S2 were first evaluated ( Supporting Information Figures S33, S34, and Table S1). For both isomers, as revealed by the fluorescence spectra, no emission was observed in pure acetone. Upon the increase of the fraction of water as poor solvent (f, vol %) from 10% to 50%, only slight increase of the emission intensity was observed. By further increasing the f to 60% and finally to 95%, the remarkable enhancement in the emission intensity was revealed, thus indicating the typical AIE behavior. However, different from TPE-S1 which maintains cyan emission during the aggregation process (Figure 5a and Supporting Information Figure S33a), TPE-S2 revealed an obvious bathochromic shift from blue (458 nm) to cyan (472 nm) as f was increased from 70% to 80%, indicating a hierarchical aggregation behavior (Figure 5d and Supporting Information Figure S33b). Such interesting phenomenon might be attributed to the fact that the steric hindrance of the rigid pillar5arene wheel prevented the intermolecular aggregation of the nearby TPE unit when f < 80%, resulting in a blue emission in the initial aggregate state. The further increase of water made the intermolecular aggregation possible, thus leading to a bathochromic shift in the cyan emission. Figure 5 | Fluorescence spectra (λex = 330 nm) and photographs (upon UV lamp excitation at 365 nm) of (a) TPE-S1 and (d) TPE-S2 in acetone/H2O with different H2O fractions (c = 0.01 mM). SEM images of TPE-S1 (f = 70%, b; f = 90%, c) and TPE-S2 (f = 70%, e; f = 90%, f) in different aggregate Download figure Download PowerPoint To additional for such AIE phenomenon described electron analysis was further to the aggregation process of these two sequence isomers. As revealed by the SEM the of in the aggregate were observed for TPE-S1 when the f was 70% (Figure and Supporting Information Figure However, was observed for TPE-S2 when the f was 70% (Figure and Supporting Information Figure Upon further increasing the water to 90%, both sequence isomers revealed which might be attributed to the large steric hindrance of the DEP5A wheel and TPE stopper that the of large ( Supporting Information Figure Such phenomenon were in with the fluorescence spectra (Figure both of which the sequence-dependent hierarchical aggregation behavior that led to varied emission performance. With the targeted AIE-active chiral hetero3rotaxane isomers in hand, their chiroptical properties were then The spectra of both TPE-S1 and TPE-S2 that there was no obvious chirality information from the DEP5A wheel to the TPE stopper in solution and aggregate as revealed by the fact that only attributed to the DEP5A wheel were observed. that chiral information would be more in the solid the spectra of TPE-S1 and TPE-S2 in solid were then As revealed by the spectra, for both TPE-S1 and TPE-S2, were which was with that in solution and aggregate state. Moreover, at which were to the TPE were found, chirality information in the solid (Figure and Supporting Information Figure is that the at of TPE-S2 were of more chirality information in Figure 6 | and spectra of (a) and (b) in solution = aggregate = and solid spectra at the of Download figure Download PowerPoint by the chirality information in the the sequence engineering in the CPL performance of these AIE-active chiral hetero3rotaxane isomers was then investigated. CPL of these two sequence isomers TPE-S1 and TPE-S2 (Figure that both of them revealed CPL at that from the TPE indicating successful chirality information from the chiral DEP5A wheel to the TPE As the Rp- TPE-S1 resulted in CPL with is, a CPL for the Rp- TPE-S1 was Sp- TPE-S1 a again a pure CPL The of Rp- TPE-S1 and Sp- TPE-S1 were and respectively. More