Heng-Yi Zhang

A Twin‐Axial Hetero[7]rotaxane

Rotaxanes are challenging and interesting because of their potential applications in nanotechnology and molecular machines. Template synthesis has been widely used to realize more efficient synthesis of rotaxanes, while various protocols have been reported such as the popular “threading followed by stoppering”, “slippage”, and “clipping” approaches. However, the synthesis of high-order rotaxanes still remains a challenge. 4] In this respect, it is very difficult to obtain heterorotaxanes with two or more similar rings, as well as [n]rotaxanes with more than one axle molecule threaded through the same ring. Macrocyclic polyethers have been applied widely in the construction of various rotaxanes because of the unique complexation behavior of the macrocycles toward threadlike guests such as secondary benzyl or alkyl ammonium ions. Herein, we propose a strategy to integrate two different macrocyclic polyethers into one [n]rotaxane molecule by simultaneous twin-axial and single-axial rotaxanation (Figure 1). We firstly designed a four-component self-assembly system, which involves two macrocyclic polyethers, namely bis(p-phenylene-34-crown-10) (BPP34C10) and benzo-21-crown-7 (B21C7) and two secondary ammonium compounds 1 and 2. When all materials are mixed, the [3]pseudorotaxane 22@BPP34C10 [8b, 9] and the [2]pseudorotaxane 1@B21C7 are formed exclusively. The two pseudorotaxanes contain azide and alkyne groups as potential reactive sites. With the pseudorotaxanes in hand, the copper(I)-catalyzed Huisgen alkyne–azide 1,3-dipolar cycloaddition (CuAAC “click” reaction), which has often been used in rotaxane synthesis, was performed. In the obtained hetero[7]rotaxane, four B21C7 rings can be stoppered by the outer phenyl groups, while the central BPP34C10 is “cascadestoppered” by the B21C7 rings. The combination of selfassembly and synthetic strategy ensures the correct position for two kinds of rings in the final product. In sharp contrast, the synthesis of higher-order rotaxanes often needs the corresponding components to contain more binding sites, which increases the synthetic difficulty; a high association constant is needed to obtain the dynamic multicomponent complex, which is required in the common “threading followed by stoppering” protocol. Our method utilizes the concept of modularization, which means that the high-order hetero[7]rotaxane is synthesized by using the highly efficient CuAAC reaction among the preorganized building blocks. The preparation of 1 and 2 involves the condensation of the corresponding benzaldehyde with an alkyl or benzyl amine, and then reduction, protonation, and anion-exchange steps. We performed H NMR experiments to confirm the formation of self-assembly systems in solution. It has been reported that BPP34C10 can form a 1:2 complex with secondary dibenzyl ammonium ions. From the characteristic complexation-induced chemical shifts in the H NMR spectra, the formation of [3]pseudorotaxane 22@BPP34C10 and [2]pseudorotaxane 1@B21C7 was confirmed, when the axle molecules and corresponding ring components were mixed (see Figures S28 and S38 in the Supporting Information). The signals of He and Hf in 22@BPP34C10 as well as those of Ha and Hc in 1@B21C7 can be identified from the H NMR spectrum of a 2:2:2:1 mixture of 1, 2, B21C7, and BPP34C10 (Figure 2b). These observations indicate that the two pseudorotaxanes still exist as the dominant species in the four-component system. Moreover, the H NMR spectrum of a 1:1:1:1 mixture of 1, 2, B21C7, and dibenzo-24-crown-8 (DB24C8) shows that two pseudorotaxanes 1@B21C7 and 2@DB24C8 are predominantly formed in this four-component system (see Figure S30 in the Supporting Information). The CuAAC reaction of 1@B21C7 and 22@BPP34C10 in the presence of Cu(MeCN)4PF6 and 2,6-lutidine in dichloromethane at room temperature, and subsequent alkylation of the 1,2,3-triazole resulted in the successful synthesis of hetero[7]rotaxane 5, which was isolated in moderate yield after purification by column chromatography. The HRMS spectrum of 5 shows a signal at m/z 663.2944, which corresponds to the product after loss of six PF6 ions; this finding is consistent with the calculated mass isotope distribution (Figure S52 in the Supporting Information). The methylation of the 1,2,3-triazole was performed to enhance the polarity of the final product for more efficient isolation of the rotaxane from the reactants. To further confirm the structure of hetero[7]rotaxane 5, we synthesized hetero[4]rotaxane 4, which contains one DB24C8 and two B21C7 rings, as well as [3]rotaxane 3 with two B21C7 rings, by following a similar procedure. We assigned all the resonances in 3 and 4 by analyzing their 1D and 2D NMR spectra. The protons H1, H2, H3, and Hc on the axle component in 3 are shifted upfield when compared with free 6, while Ha and Hb adjacent to the outer ammonium site are shifted downfield (Figure 3c) because of the complexation of the B21C7 ring. It is notable that protons H4 in 3 can be detected because of the stabilizing effect of the hydrogen bonding interactions between the crown ether and the ammonium hydrogen atoms. On the other hand, we noted that not only the central ammonium hydrogen atoms H8 in 3 cannot be detected, but also that H6, H7, and Hf remain mostly [*] Z.-J. Zhang, Prof. Dr. H.-Y. Zhang, H. Wang, Prof. Dr. Y. Liu Department of Chemistry State Key Laboratory of Elemento-Organic Chemistry Nankai University, Tianjin, 300071 (P.R. China) E-mail: yuliu@nankai.edu.cn

Mechanically selflocked chiral gemini-catenanes

Mechanically interlocked and entangled molecular architectures represent one of the elaborate topological superstructures engineered at a molecular resolution. Here we report a methodology for fabricating mechanically selflocked molecules (MSMs) through highly efficient one-step amidation of a pseudorotaxane derived from dual functionalized pillar[5]arene (P[5]A) threaded by α,ω-diaminoalkane (DA-n; n=3–12). The monomeric and dimeric pseudo[1]catenanes thus obtained, which are inherently chiral due to the topology of P[5]A used, were isolated and fully characterized by NMR and circular dichroism spectroscopy, X-ray crystallography and DFT calculations. Of particular interest, the dimeric pseudo[1]catenane, named ‘gemini-catenane, contained stereoisomeric meso-erythro and dl-threo isomers, in which two P[5]A moieties are threaded by two DA-n chains in topologically different patterns. This access to chiral pseudo[1]catenanes and gemini-catenanes will greatly promote the practical use of such sophisticated chiral architectures in supramolecular and materials science and technology.

A proton-triggered ON-OFF-ON fluorescent chemosensor for Mg(II) via twisted intramolecular charge transfer.

A novel fluorescent chemosensor has been synthesized and shows interesting fluorescent ON-OFF-ON processes through mediating its twisted intramolecular charge transfer (TICT) state. An exclusively fluorescent enhancement is observed for Mg (2+).

A Double Plug–Socket System Capable of Molecular Keypad Locks through Controllable Photooxidation

Two robust divalent complexes have been successfully constructed by using complementary rigid spacers (anthracene vs. 1,4,5,8-naphthalenediimide (NDI)) and two pairs of [24]crown-8 ethers and secondary dialkylammonium functionalities as binding motifs. It was demonstrated that properly selected, rigid spacers are more efficient than flexible ones for achieving strong multivalent association. This is presumably due to the preorganization of the rigid spacers, the cooperation between charge-transfer interactions of rigid spacers, and the complexation of the binding motifs. Furthermore, the intermolecular photoinduced electron transfer (PET) between rigid spacers in these robust complexes could be switched on and off by modulating their complexation through acid-base reactions, which is reminiscent of a plug-socket system capable of electron transfer. In addition, the self-sensitized photooxidation of the divalent host with anthracene as a spacer can be completely inhibited after complexation with the divalent guests that contain NDI as spacers. This process could also be understood by invoking intermolecular PET and could be turned on and off through acid-base reactions. The photophysical and photochemical properties of these robust complexes have been interpreted as molecular keypad locks with alarm systems. Thus, a double plug-socket system and molecular keypad locks were successfully integrated inside robust multivalent systems and then the normal molecular devices were endowed with logic functions.

Thermodynamic origin of selective binding of β-cyclodextrin derivatives with chiral chromophoric substituents toward steroids.

Two β-cyclodextrin derivatives with chiral chromophoric substituents, that is, L- (1) and D-tyrosine-modified β-cyclodextrin (2), were synthesized and fully characterized. Their inclusion modes, binding abilities, and molecular selectivities with four steroid guests, that is, cholic acid sodium salt (CA), deoxycholic acid sodium salt (DCA), glycochoic acid sodium salt (GCA), and taurocholic acid sodium salt (TCA), were investigated by the circular dichroism, 2D NMR, and isothermal titration microcalorimetry (ITC). The results obtained from the circular dichroism and 2D NMR showed that two hosts adopted the different binding geometry, and these differences subsequently resulted in the significant differences of molecular binding abilities and selectivities. As compared with native β-cyclodextrin and tryptophan-modified β-cyclodextrin, host 2 showed the enhanced binding abilities for CA and DCA but the decreased binding abilities for GCA and TCA; however, host 1 showed the decreased binding abilities for all four bile salts. The best guest selectivity and the best host selectivity were K(S)(2-DCA)/K(S)(2-TCA) = 12.6 and K(S)(2-CA)/K(S)(1-CA) = 10, respectively, both exhibiting great enhancement as compared with the corresponding values of the previously reported L- and D-tryptophan-modified β-cyclodextrins. Thermodynamically, it was the favorable enthalpic gain that led to the high guest selectivity and host selectivity.

Self‐Sorting of Four Organic Molecules into a Heterowheel Polypseudorotaxane

The social self-sorting supramolecular assembly is described by non-covalent interactions among four organic components. Toward this goal, a series of self-sorting systems have been investigated by mixing two or three different compounds; naphthyl-bridged bis(α-cyclodextrin), N,N-dioctyl-4,4-bipyridinium, 2,6-dihydroxynaphthalene, and cucurbit[8]uril. The influence of alkyl chains of viologen derivatives and the binding abilities of these systems have also been studied. Their integrative self-sorting led to the exclusive formation of the purple supramolecular heterowheel polypseudorotaxane. The heterowheel polypseudorotaxane is a thermodynamically stable self-sorted product, and consists of two different macrocycles with three sorts of different non-covalent interactions. Its structure was established by NMR spectroscopy and UV/Vis absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light-scattering (DLS), diffusion-ordered spectroscopy (DOSY), and viscosity measurements.

Characterisation and antiproliferative activity of irinotecan and sulphonatocalixarene inclusion complex

The interaction between water-soluble sulphonatocalix[4]arene (SC4A) and irinotecan (CPT-11) was investigated by using UV spectrophotometry. Inclusion complex of SC4A with CPT-11 was confirmed by 1H NMR and DSC analysis. Water solubility study showed that SC4A has remarkable solubilisation on CPT-11 and the complex has good water solubility. The antiproliferative activity of the complex was evaluated. The results showed that the complexation of CPT-11 with SC4A increases the antiproliferative activity of CPT-11.

Insights into the Difference Between Rotaxane and Pseudorotaxane

Rotaxane and pseudorotaxane are two types of mechanically interlocked molecular architectures, and there is a clear topological difference and boundary between them. In this work, a suggested [2]rotaxane 1⊂α-CD was constructed based on axle molecule 1 bearing two terminal ferrocene groups and a wheel component α-cyclodextrin (α-CD), but the result obtained indicated that the ferrocene group cannot prevent α-CD dethreading under UV irradiation. That is, 1⊂α-CD is just a pseudo[2]rotaxane. Furthermore, the two ferrocene groups in 1⊂α-CD were encapsulated by two cucurbit[7]uril (CB[7]) units to obtain a heteropseudo[4]rotaxane 1⊂α-CD⋅2CB[7]. This heteropseudo[4]rotaxane displayed high stability towards harsh temperatures and the isomerization of azobenzene in 1, so it can be regarded as a [2]rotaxane. In this [2]rotaxane, the stoppers are not the bulky groups covalently bonded to the axle, but the cyclic CB[7] units connected through noncovalent interactions.

Supramolecular Nanoassemblies of an Amphiphilic Porphyrin–Cyclodextrin Conjugate and Their Morphological Transition from Vesicle to Network

An amphiphilic compound, 5-(4-dodecyloxyphenyl)-10,15,20-tri(permethyl-β-CD)-modified Zn(II)-porphyrin (1; β-CD = β-cyclodextrin), was synthesized by means of the click reaction of an alkylated Zn-porphyrin derivative with 6-deoxy-6-azidopermethyl-β-CD. The complexation between 1 and tetrasodium tetraphenylporphyrintetrasulfonate (5) with different molar ratios led to the formation of two distinctly different nanoarchitectures, which were proven to be vesicle and network aggregates, respectively, by using dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. On the basis of the results of the time-dependent TEM studies, fluorescence, and NMR spectroscopic measurements, we have determined that the mechanism of the morphology transition from vesicles to networks is controlled by the stepwise complexation of 1 with 5. Furthermore, these supramolecular nanoarchitectures show the controlled- release property of doxorubicin as potential candidates for drug delivery.

Unique conformation and packing structure of p-sulfonatocalix(5)arene induced by 1,2-bis(pyridinium)ethane compounds

In the presence of 1,2-bis(4,4-dipyridinium)ethane, p-sulfonatocalix[5]arene (C5AS) adopts an unseen partial-cone conformation to form back-to-back dimers, whereas C5AS crystallizes in face-to-face dimers to form a wavy layer, rather than the expected bilayer, arrangement upon complexation with 1,2-bis(pyridinium)ethane.