Letter pubs.acs.org/OrgLett
A Braided Hetero[2](3)rotaxane Chuan Gao, Zhou-Lin Luan, Qi Zhang, Si-Jia Rao, Da-Hui Qu,* and He Tian Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China S Supporting Information *
ABSTRACT: A novel braided hetero[2](3)rotaxane is demonstrated by integrating the braided structure and mechanically interlocked rotaxane, in which a heterotritopic linear tris(dialkylammonium) guest penetrates a heterotritopic tris(crown ether) host, resulting in the formation of braided pseudohetero[2](3)rotaxane with different crossing and threading points. Then a braided hetero[2](3)rotaxane is constructed through the “CuAAC” click reaction.
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toward more functional molecular switches or machines.14 Our goal is to integrate the braided and threaded structures in a single molecule to construct a unique mechanically interlocked braided molecule (Scheme 1). It should be noted that the
imicking natural occurring structures by artificial synthetic routes is one of the most appealing but also challenging themes,1 especially the entwined and crossing molecular knots found throughout biology.2 One of the most well-known examples is the double-helical backbone of DNA, which has been widely investigated and mimicked since its identification.3 Meanwhile, threaded and entwined structures can also be found within proteins, also considered as “open braid” because of their disconnected terminal groups.4 Creating novel molecular braids or entwined structures by an artificial organic synthesis strategy would support a vital understanding for these natural homologous systems.1e Although these natural braided structures become increasingly accessible and controllable for scientists, it is still a challenge to create such highly programmed entwined and crossing molecules by artificial synthetic routes.5 Generating crossing points is the essential key to these braided molecular structures.1c−e,6 Chemists have introduced some reliable and efficient strategies for spontaneous formation of crossing points through template routes, including metal-ion coordination templates,7 hydrogen-bond motifs,8 active templates,9 and some other strategies.10 These template-induced crossing molecular blocks could be further built by a topological strategy toward the construction of many elegant molecular braids.1c−e,6c,9b Some of these entwined structures even bear promising operating behaviors simulating the biological functional molecules,1e showing a bright prospect for biological molecules with specific functions. However, few efforts have been made in the simultaneous presence of crossing and threading points,10b which bears wide existence especially in the proteins.4 Rotaxanes,11,12 a species of mechanically interlocked molecules consisting of macrocycles encircling on the threadshaped components with terminal stoppers, have attracted remarkable attention due to their unique threaded structures. Numerous rotaxanes have been fabricated with highly complicated structures12 via the well-known template-directed strategy,13 and the increasing structural complexity also brings incalculable possibilities for further design and modification © 2017 American Chemical Society
Scheme 1. Schematic Representation of the Formation and Structures of [2](3) Braid, (Pseudo)[2]rotaxane, and Proposed Braided (Pseudo)[2](3)rotaxane in Which Different Crossing and Threading Points Can Be Introduced
diversities of the host−guest systems can provide the braided heterorotaxane system with a variety of different crossing and threading points. Moreover, inspired by the specific sort of basic group in gene segment, we also expect to introduce two or more species of macrocycles into the braided (pseudo) [2]rotaxane toward an “encoded” braided hetero[2]rotaxane as shown in Scheme 1. Herein, we report the design, synthesis, and charaterization of a braided hetero[2](3)rotaxane 4 as shown in Scheme 2a, in which the simultaneous presence of three crossing points and three threading points was realized in a single self-assembling molecular system, and its synthesis could be undertaken by an efficient one-pot strategy. Considering the unique flexible molecular structures of macrocyclic polyethers and their reliable Received: June 18, 2017 Published: July 11, 2017 3931
DOI: 10.1021/acs.orglett.7b01853 Org. Lett. 2017, 19, 3931−3934
Letter
Organic Letters
tris(dialkylammonium) guest 2 contain different crown ether rings and dialkylammonium ions, respectively, it is necessary to investigate the self-assembly process between the two components. First, the multiple host−guest interactions of tris(crown ether) host 1 and different DBA and BAA recognition sites were thoroughly studied by 1H NMR spectroscopy. Moreover, the pseudorotaxanes formed between the heterotritopic tris(dialkylammonium) guest 2 with B21C7 and DB24C8 were also investigated (Figures S1 and S2). These results clearly showed that the host−guest combination of B21C7 and BAA site would not affect the pseudorotaxane formation between the DB24C8 and DBA site, indicating that the self-assembly of this kind of system occurred within a selective and well-organized self-sorting mode, even in the more complicated multiple host−guest systems. Meanwhile, it also helped our further understanding of the chemical shifts about the multilevel self-assembly of host 1 and guest 2. Subsequently, two-component self-assembly between tris(crown ether) host 1 and tris(dialkylammonium) guest 2 was investigated by 1H NMR spectroscopy (Figure 1). Upon mixing
Scheme 2. (a) Preparation of Braided Hetero[2](3)rotaxane 4 with Compound 1 and Compound 2 via One-Pot Synthesis. (b) Schematic Representation of Thread-Shaped Compound 5 and Hetero[4]rotaxane
Figure 1. Partial 1H NMR spectra (400 MHz, 298 K, 3.0 mM) of (a) compound 1 in CD3CN, (b) a 1:1 mixture of compound 1 and compound 2 in CD3CN, (c) compound 2 in CD3CN, and (d) a 1:1 mixture of compound 1 and compound 2 in solvent (CD3CN/CDCl3 = 1:1).
noncovalent interactions with dialkyl ammounium ions, a heterotritopic tris(crown ether) host 1 was designed with one DB24C8 macrocycle in the middle, which was covalently bonded with two B21C7 macrocycles at each side via ester bonds. Meanwhile, a heterotritopic linear tris(dialkylammonium) guest 2 was designed with one dibenzylammonium (DBA) site in the middle and two benzylalkylammonium (BAA) sites at both sides. Significantly, although there were numerous possibilities of different self-assembling modes formed by host 1 and guest 2, the pseudo[2](3)rotaxane 3 is the major self-assembly shown in Scheme 2a, owing to the highly selective host−guest interactions among the mixed components containing DB24C8, B21C7, DBA and BAA moieties, respectively, which were driven through a so-called self-sorting process.15 Then, the facile copper(I)-catalyzed alkyne−azide cycloaddition (CuAAC) click reaction with benzyl azide afforded the target hetero[2](3)rotaxane 4 in an efficient one-pot mode. We foresee this work to be a significant achievement for the construction of simultaneously entwined and threaded molecules toward bioinspired artificial complicated topological structures. The syntheses of the target hetero[2](3)rotaxane 4 and the chemical structures of its corresponding thread-shaped molecule 5 and a reference hetero[4]rotaxane 6 are shown in Scheme 2. As the tris(crown ether) host 1 and the
2 with 1 at a molar ratio of 1:1 in CD3CN (Figure 1b), the signals of the aromatic protons (H3, H4, H11, H12) in the DBA and BAA sites of 2 exhibited significant changes and gave the corresponding upfield shifts with Δδ of −0.11, −0.33, −0.28, and −0.27 ppm, respectively, due to the shielding effect of crown ether rings. Meanwhile, the protons H2 and H15 in the DBA and BAA sites of 2 shifted downfield with a Δδ of 0.43 ppm for H2 because of the hydrogen-bonding interactions with the oxygen atoms of crown ethers. Compared with the 1H NMR spectrum of tris(crown ether) host 1 (Figure 1a), the aromatic protons (Ha, He, Hf, Hg) of the crown ether almost all slightly shifted upfield because of the stabilizing effect of the hydrogen-bonding interaction between the crown ether and binding sites on guest 2. Moreover, it is noteworthy that the signal of methylene hydrogen atoms Hd of the linkage between ring moieties in host 1 split from single peak to multiple peaks, indicating their different surrounding chemical environments, which was created by the unique entwined structure of hetoropseudo[2](3)rotaxane 3. Considering the incomplete combination between host 1 and guest 2 in CD3CN, we also 3932
DOI: 10.1021/acs.orglett.7b01853 Org. Lett. 2017, 19, 3931−3934
Letter
Organic Letters investigated the 1H NMR spectrum (Figure 1d) of the preassembly process in the less polar solvent (CD3CN/ CDCl3 = 1:1). After 5 min of mixing host 1 and guest 2, the signals of the aromatic protons (H3, H4, H11, H12) and the proton H15 almost completely changed, owing to the solvent effect. All of these observations suggested the successful and efficient preassembly of braided heteropseudo[2](3)rotaxane 3 by a highly encoded self-assembly mode among macrocyclic hosts, DB24C8 and B21C7, and two kinds of secondary ammonium sites. Then host 1 was first mixed with 1 equiv of guest 2 in CH2Cl2/acetone (v/v = 2:1, 1.0 mM), and the mixture was stirred for 24 h to obtain heteropseudo[2](3)rotaxane 3. The subsequent “CuAAC” stoppering reaction can yield the target triply interlocked hetero[2](3)rotaxane 4 with a moderate separated yield of 32%. The high-resolution ESI-MS spectrum of rotaxane 4 showed signals at m/z 1259.5970 and 791.4070, corresponding to the species after loss of two and three PF6− ions, respectively. Moreover, the structure of the hetero[2](3)rotaxane 4 also was confirmed by 1H NMR spectroscopy (Figure 2b). The
in hetero[2](3)rotaxane 4 were all split due to the formation of the interlocked structure and the effect of the linear axle. Moreover, the other aromatic hydrogen atoms Ha, He, Hf, and Hg were shifted upfield compared with noninterlocked host compound 1 because of the effects of the hydrogen-bonding interactions between crown ether and binding sites on the axle component. Remarkably, the signals of the methylene proton Hd in the linker part of the two rings in compound 4 split into two double peaks (δ = 5.26 and 5.17 ppm) from a single peak, indicating proton Hd existed as diastereotopic methylene hydrogens.16 This is the characteristic change of rotaxane 4, which is different from other possible self-assemblies. The obvious changes of chemical shift show the successful formation of triply interlocked hetero[2](3)rotaxane 4 rather than other supramolecular architectures. It should be noted that hetero[2](3)rotaxane 4 existed as two stereoisomers because the tris(crown ether) component in hetero[2](3)rotaxane 4 has two conformations due to the rotation of ester bond being restricted, which was different from the case in the free symmetric tris(crown ether) host 1. The two stereoisomers (Figure S3) were also observed in a 1:1 molar ratio according to the 1H NMR spectrum of compound 4, in which the signal of aromatic Hb in B21C7 rings split into two peaks (Figure 2b). To further confirm the structure of hetero[2](3)rotaxane 4, a reference hetero[4]rotaxane 6 containing thread-shaped component 5, one DB24C8 ring, and two B21C7 rings was obtained by utilizing the same approach as hetero[2] (3)rotaxane 4 (Scheme 2b). Then the structure of hetero[4]rotaxane 6 was confirmed by the 1H NMR spectrum (Figure 2c and Figure S4). The signals of H2 and H15 in the DBA and BAA sites all shifted downfield (Δδ = 0.43 and 0.37 ppm, respectively) compared with noninterlocked 5. Furthermore, the signals of aromatic protons H3 and H12 in DBA and BAA sites shifted upfield with a Δδ of −0.12 and −0.17 ppm, respectively. Correspondingly, the signals of H4 and H11 in DBA and BAA sites underwent clearer changes, shifting upfield with a Δδ of −0.27 and −0.12 ppm. In the 1H NMR spectrum of hetero[2](3)rotaxane 4 (Figure 2b), the chemical shifts of protons (H2, H3 and H4) on the DBA site were consistent with those in hetero[4]rotaxane 6, meaning the DB24C8 is still located on the DBA site. Meanwhile, the signals of protons (H11 and H12) were also observed in similar chemical shifts as in hetero[4]rotaxane 6, which suggested the two B21C7 rings are located on the BAA sites. These clear changes and comparisons of chemical shifts can not only confirm the formation of hetero[4]rotaxane 6 but are also helpful in analyzing the structure of braided hetero[2](3)rotaxane 4. In conclusion, by combining the chemical topologies of the braided molecules and mechanically interlocked molecules, we have demonstrated the design, synthesis, and characterization of a braided hetero[2](3)rotaxane. It should be emphasized that the existence of the current diversified host−guest systems can endow these kinds of braided and multiply interlocked rotaxane systems with entwined diversity and complexity of different crossing and threading points, which can enrich the field of supramolecular chemistry. The study of braided rotaxanes with increasing structural complexity is underway.
Figure 2. Partial 1H NMR spectra (CD3CN, 400 MHz, 298 K) of (a) compound 1, (b) braided hetero[2](3)rotaxane 4, (c) hetero[4]rotaxane 6, and (d) thread-shaped compound 5.
signal of proton H19 (δ = 7.75 ppm) on the axle component exhibited a single peak indicating the formation of triazole groups. Compared with the thread-shaped compound 5 (Figure 2d), the signals of aromatic protons H3 and H4 in the DBA site of compound 4 shifted upfield with a Δδ of −0.12 and −0.31 ppm, respectively, and the signals of the aromatic protons H11, H12 in the BAA sites of 4 also shifted upfield with a Δδ of −0.27 and −0.29 ppm, respectively. The signals of protons H15 and H13 adjacent to the BAA centers shifted downfield with a Δδ of 0.44 and 0.03 ppm, respectively, and the signals of H2 adjacent to the DBA center shifted downfield with a Δδ of 0.43 ppm due to their hydrogen-bonding interactions with the oxygen atoms of macrocycles. In addition, the signals of protons H5 and H10 on the spacer of axle component of 4 underwent clear changes, shifting upfield to 3.84 ppm from 4.00 ppm (Δδ = −0.16 ppm) due to the shielding effect of crown ethers. These significant changes indicated that three recognition binding sites all interpenetrate into their corresponding crown ether rings. In comparison with the 1H NMR spectrum of noninterlocked analogue host 1 (Figure 2a), the signals of the methylene hydrogen atoms on crown ether rings 3933
DOI: 10.1021/acs.orglett.7b01853 Org. Lett. 2017, 19, 3931−3934
Letter
Organic Letters
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b01853. Details of experimental procedures and characterization data (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Da-Hui Qu: 0000-0002-2039-3564 He Tian: 0000-0003-3547-7485 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by NSFC/China (21672060, 21421004, 21420102004), the Fundamental Research Funds for the Central Universities (WJ1616011, WJ1213007, 222201717003), and the Programme of Introducing Talents of Discipline to Universities (B16017).
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