Kinetic versus thermodynamic control during the formation of [2]rotaxanes by a dynamic template-directed clipping process

A template-directed dynamic clipping procedure has generated a library of nine [2]rotaxanes that have been formed from three dialkylammonium salts-acting as the dumbbell-shaped components-and three dynamic, imino bond-containing, [24]crown-8-like macrocycles-acting as the ring-shaped components-which are themselves assembled from three dialdehydes and one diamine. The rates of formation of these [2]rotaxanes differ dramatically, from minutes to days depending on the choice of dialkylammonium ion and dialdehyde, as do their thermodynamic stabilities. Generally, [2]rotaxanes formed by using 2,6-diformylpyridine as the dialdehyde component, or bis(3,5-bis(trifluoromethyl)benzyl)ammonium hexafluorophosphate as the dumbbell-shaped component, assembled the most rapidly. Those rotaxanes containing this particular electron-deficient dumbbell-shaped unit, or 2,5-diformylfuran units in the macroring, were the most stable thermodynamically. The relative thermodynamic stabilities of all nine of the [2]rotaxanes were determined by competition experiments that were monitored by (1)H NMR spectroscopy.     

Degenerate [2]rotaxanes with electrostatic barriers

A synthetic approach to the preparation of [2]rotaxanes (1-5·6PF(6)) incorporating bispyridinium derivatives and two 1,5-dioxynaphthalene (DNP) units situated in the rod portions of their dumbbell components that are encircled by a single cyclobis(paraquat-p-phenylene) tetracationic (CBPQT(4+)) ring has been developed. Since the π-electron-deficient bispyridinium units are introduced into the dumbbell components of the [2]rotaxanes 1-5·6PF(6), there are Coulombic charge-charge repulsions between these dicationic units and the CBPQT(4+) ring in the [2]rotaxanes. Thus, the CBPQT(4+) rings in the degenerate [2]rotaxanes exhibit slow shuttling between two DNP recognition sites on the (1)H NMR time-scale on account of the electrostatic barrier posed by the bispyridinium units, as demonstrated by variable-temperature (1)H NMR spectroscopy. Electrochemical experiments carried out on the [2]rotaxanes 1·6PF(6) and 2·6PF(6) indicate that the one-electron reduced bipyridinium radical cation in the dumbbell components of the [2]rotaxanes serves as an additional recognition site for the two-electron reduced CBPQT(2(˙+)) diradical cationic ring. Under appropriate conditions, the ring components in the degenerate rotaxanes 1·6PF(6) and 2·6PF(6) can shuttle along the recognition sites--two DNP units and one-electron reduced bipyridinium radical cation--under redox control.     

Post-assembly processing of [2]rotaxanes

The concept of using [2]rotaxanes that carry one or more surrogate stoppers which can subsequently be converted chemically into other structural units, resulting in the formation of new interlocked molecular compounds, is introduced and exemplified. Starting from simple NH2(+)-centered/crown-ether-based [2]rotaxanes, containing either one or two benzylic triphenylphosphonium stoppers, the well-known Wittig reaction has been employed to make, 1) other [2]rotaxanes, 2) higher order rotaxanes, 3) branched rotaxanes, and 4) molecular shuttles--all isolated as pure compounds, following catalytic hydrogenations of their carbon-carbon double bonds, obtained when aromatic aldehydes react with the ylides produced when the benzylic triphenylphosphonium derivatives are treated with strong base. The two starting [2]rotaxanes were characterized fully in solution and also in the solid state by X-ray crystallography. The new interlocked molecular compounds that result from carrying out post-assembly Wittig reactions on two [2]rotaxanes were characterized by (dynamic) 1H NMR spectroscopy. In the case of a molecular shuttle in which the crown ether component is dibenzo[24]-crown-8 (DB24C8), shuttling is slow on the 1H NMR timescale, even at high temperatures. However, when DB24C8 is replaced by benzometaphenylene[25]-crown-8 as the ring component in the molecular shuttle, the frequency of the shuttling is observed to be around 100 Hz in [D4]methanol at 63 degrees C.     

Facile synthesis of rotaxanes through condensation reactions of DCC-[2]rotaxanes

[reaction: see text] In this Letter, we present an easy method for the synthesis of rotaxanes using a novel DCC-[2]rotaxane. The DCC-[2]rotaxane is composed of dibenzo-24-crown-8 ether, an amino acid tether, and di-tert-butyl phenyl rings as blocking groups. It is relatively stable and can be purified by column chromatography. A series of model rotaxanes were obtained in good yields by condensing the DCC-[2]rotaxanes with N-(2-aminoethyl)-3,5-di-tert-butylbenzylamide in acetonitrile and chloroform.     

Synthesis and characterization of a metallocycle-based molecular shuttle

Kinetically stable metallocycle-based molecular shuttles of [2]rotaxanes 4a and 4b, along with [3]rotaxanes 5a and 5b, have been prepared using the rhenium(I)-bridged metallocycle 2 and the dumbbell components containing two stations, 3a and 3b. The rotaxanes were self-assembled by hydrogen bonding interactions upon heating a Cl(2)CHCHCl(2) solution containing their components at 70 degrees C. Each rotaxane was isolated in pure form by silica gel chromatography under ordinary laboratory conditions and fully characterized by elemental analysis and various spectroscopic methods. The (1)H NMR signals for the amide NH and the methylene -(CH(2))(4)- of the station were considerably changed when occupied by the metallocycle. In [2]rotaxane 4b, which has a larger naphthyl spacer, the occupied and unoccupied stations gave widely separated signals in the (1)H NMR spectroscopy at room temperature, but averaged signals of two stations were observed in [2]rotaxane 4a, which has a smaller phenyl spacer. This is attributed to the shuttling of the metallocycle between two stations. The coalescence temperature experiment gave a shuttling rate of approximately 670 s(-)(1) at 19 degrees C in CDCl(3), corresponding to an activation free energy (DeltaG()) of 13.3 kcal/mol. With respect to the relative position of the chloride in the rhenium(I) center, two diastereomers are possible in the [2]rotaxane and three diastereomers are possible in the [3]rotaxane. In fact, the rotaxanes exist as diastereomeric mixtures in nearly equal amounts of all possible diastereomers on the basis of the amide NH signals of the station in the (1)H NMR spectroscopy.     

Relative rotational motion between alpha-Cyclodextrin Derivatives and a stiff axle molecule

Novel [2]rotaxanes bearing alpha-cyclodextrin (alpha-CD) derivatives and a diphenylacetylene axis molecule with trinitrobenzene as a bulky stopper have been prepared to investigate the relative rotary movement of a ring relative to an axis molecule and that of an axis molecule in a ring by NMR techniques. [2]Rotaxanes 2 and 3 were composed of alpha-CD derivatives (2: 6-phenyl-amide-alpha-CD; 3: 6-stilbene-amide-alpha-CD). The protons of alpha-CDs in rotaxanes were thoroughly assigned by the two-dimensional NMR techniques (TOCSY, COSY, ROESY, HMQC, and HMBC). The protons of alpha-CD in rotaxane 1 did not show splitting, whereas the resonance peak shifts and splitting for the corresponding protons of alpha-CD derivatives in rotaxanes 2 and 3 were observed by the shielding and deshielding effects from a diphenylacetylene axis molecule. The splitting of resonance peaks was closely related to the rotary movements of alpha-CDs and an axis molecule. We supposed that alpha-CD in rotaxane 1 rotates freely around a diphenylacetylene axis molecule, and vice versa, whereas the rotary movement of alpha-CD derivatives and the axis molecules of rotaxanes 2 and 3 were restricted by the steric repulsion between the substituent group of alpha-CD and the stopper group of an axis molecule. To estimate the relative rotary movement of CDs and an axis molecule in rotaxanes, the rotational correlation time (tauc) of rotaxanes was measured by 13C NMR. The results indicate that the corresponding rotary movement of the modified alpha-CD and the axis molecules in rotaxanes 2 and 3 depends on the size of the substituent group.     

1]rotaxanes and pretzelanes: synthesis, chirality, and absolute configuration [In Process Citation

The synthesis of aliphatically bridged [1](n)rotaxanes and (n)pretzelanes in preparative yields and the dependency of their chiroptical properties on the length (n) of their bridge are reported. A cycloenantiomeric bis(sulphonamide)[2]rotaxane with a sulphonamide group in its axle and its wheel was intramolecularly dialkylated by homologous bifunctional oligomethylene reagents to form chiral [1](n)rotaxanes bearing bridges of different lengths (n) between the axle and the wheel. Intramolecular dialkylation by 1,omega-dibromoalkanes of a topologically chiral bis(sulphonamide)[2]catenane with a sulphonamide group in both of the macrolactam rings leads to pretzel shaped molecules ((n)pretzelanes) with homologous bridges between the two macrocycles. Their yields decrease with decreasing length of the bridge. The shortest bridge isolated so far in reasonable amounts consists of six methylene groups ((6)pretzelane). Remarkably, a covalent connection of axle and wheel in a [2]rotaxane was successful even with much shorter bridges-down to only three methylene groups ([1](3)rotaxane). The structural changes of the [1](n)rotaxanes with decreasing bridge length is expressed by an increasing high-field shift in the 1H NMR spectra. Enantiomeric resolution of the racemates of both series was achieved in seven cases for the [1](n)rotaxanes and two for the (n)pretzelanes by use of chiral HPLC columns. The circular dichrograms of both compound families show a strong dependency on the length of the bridge. However, the shortest bridges displayed some additional unexpected deviations. A new specification of the absolute configuration of supramolecules, such as [n]catenanes, [n]rotaxanes and (n)pretzelanes is introduced together with some nomenclature additions.     

Installation of a ratchet tooth and pawl to restrict rotation in a cyclodextrin rotaxane

Eight new [2]rotaxanes have been prepared, incorporating an alpha-cyclodextrin as the rotor, a stilbene as the axle, and trinitrophenyl substituents as capping groups. Strategies have been devised to elaborate these by linking the rotor to the axle, to produce two new [1]rotaxanes. Rotational motion in a selection of these rotaxanes has been investigated through the application of two-dimensional NMR spectroscopy by performing TOCSY, DQF-COSY, ROESY and HMQC experiments. This has shown that a methoxyl group incorporated on the stilbene and a succinamide joining the stilbene and the cyclodextrin behave analogously to a ratchet tooth and pawl, respectively, to restrict rotation.     

Synthesis of linked symmetrical [3] and [5]rotaxanes having an oligomeric phenylene ethynylene (OPE) core skeleton as a π-conjugated guest via double intramolecular self-inclusion

Linked symmetrical [3] and [5]rotaxanes consisting of an oligomeric phenylene ethynylene (OPE) framework as a π-conjugated guest moiety and lipophilic permethylated α-cyclodextrins (PM α-CDs), as macrocyclic hosts have been prepared by double intramolecular self-inclusion of an OPE guest unit carrying two PM α-CDs followed by capping with bulky stopper groups using click azide-alkyne Huisgen cycloaddition or Sonogashira coupling. The structures of these linked rotaxanes were determined by MALDI-TOF mass spectrum and two-dimensional NMR spectroscopy.     

Separated and aligned molecular fibres in solid state self-assemblies of cyclodextrin [2]rotaxanes

The conformations of two [2]rotaxanes, each comprising alpha-cyclodextrin as the rotor, a stilbene as the axle and 2,4,6-trinitrophenyl substituents as the capping groups, have been examined in solution and in the solid state, using (1)H NMR spectroscopy and X-ray crystallography, respectively. In solution, introducing substituents onto the stilbene prevents the cyclodextrin from being localized over one end of the axle. Instead the cyclodextrin moves back and forth along the substituted stilbene. In the solid state, the axles of the rotaxanes form extended molecular fibres that are separated from each other and aligned along a single axis. The molecular fibres are strikingly similar to those formed by the axle component of one of the rotaxanes in the absence of the cyclodextrin, but in the latter case they are neither separated nor all aligned.     

Helic[6]arene-Based Chiral Pseudo[1]rotaxanes and [1]Rotaxanes

Chiral pseudo[1]rotaxanes and [1]rotaxanes constructed from macrocyclic arenes still remain a big challenge mainly owing to the lack of such chiral macrocycles. In this work, a new system of chiral pseudo[1]rotaxanes formed by self-inclusion of helic[6]arene containing amide linked with the terminal tertiary amines was first discovered. Based on an atom-economic stopping strategy, a pair of chiral [1]rotaxanes were conveniently obtained in almost quantitative yields by blocking the pseudo[1]rotaxanes with monobenzyl bromide of tetraphenylethene. The structures of pseudo[1]rotaxanes and [1]rotaxanes were characterized by 2D NMR spectra in solution, combined with DFT calculations. The photophysical properties further revealed the efficient chirality transfer of helic[6]arene to the tetraphenylethene moiety, compared to their unthreaded chiral isomers. The discovery of the chiral pseudo[1]rotaxanes allows for a wide and available synthesis of chiral [1]rotaxanes, and also opening a new avenue to the design of chiral supramolecular materials.     

Unidirectional threading synthesis of isomer-free [2]rotaxanes

The threading of an alpha-cyclodextrin (alpha-CyD) by an unsymmetrical dumbbell generally results in two isomeric [2]rotaxanes differing in the orientation of the alpha-CyD. In this work, two methods have been developed for the unidirectionally threading an alpha-CyD to obtain isomer-free [2]rotaxanes. These methods use the Suzuki coupling of a boronic acid derivative and a halide in aqueous alkaline solution. The conformations of the two unidirectional [2]rotaxanes-R3 and R4 were determined by 2D 1H ROESY NMR spectra. The optical spectral studies revealed that each of the two [2]rotaxanes can proceed with E/Z photoisomerization and shuttling motions of the alpha-CyD ring on the thread under alternating irradiation at 330 and 275 nm, accompanied by fluorescence intensity changes at 530 nm. The induced circular dichroism (ICD) spectra of another two analogous [2]rotaxanes R1 and R2 were also studied. Distinctive ICD signal changes resulting from the photoisomerization with respect to the movements of alpha-CyD were detected. This demonstrates that, besides the fluorescence, ICD signal is another way to identify the shuttling motions of alpha-CyD in these [2]rotaxanes.     

Pillar[5]arene-based [3]rotaxanes: Convenient construction via multicomponent reaction and pH responsive self-assembly in water

Four pillar[5]arene based [3]rotaxanes(1-4) involving two 1,4-diethoxypillar[5]arene(DEP5) rings and a dumbbell-shaped component were successfully synthesized.The dumbbell-shape molecules contain one longer bridge,two triazole sites and two multicomponent stoppers.After threading DEP5 rings with linear guests(G1-G4) which contain two benzaldehyde units,the base catalyzed three-component reaction of dimedone,malononitrile and benzaldehyde was performed to construct the stoppers and connected the pseudorotaxanes with stoppers to generate 1-4.The structures of [3]rotaxanes and their self-assembly behaviors were characterized by ~1 H NMR,~(13)C NMR,NOESY,HR-ESI-MS,DLS and TEM technologies.We hope that pillar[5]arene based [3]rotaxanes may have potential applications in drug delivery systems and molecular devices.     

Complexation in pseudorotaxanes based on alpha-cyclodextrin and different alpha,omega-diaminoalkanes by NMR diffusion measurements

The interactions of 1,4-diaminobutane (1), 1,6-diaminohexane (2), 1,8-diaminooctane (3), 1,10-diaminodecane (4), and 1,12-diaminododecane (5) with alpha-cyclodextrin (alpha-CD) were studied in aqueous solutions by NMR diffusion measurements before and after protonation. The correlation between the association constant and the length of the alkyl chain of the diamine unit was studied. The assumption that protonation on the amino groups can be used as a stopper and, as a result, to convert the pseudorotaxanes into rotaxanes was tested. In addition, other factors that can affect the pseudorotaxane stability, such as the effects of temperature, were tested. On the basis of these measurements, the following conclusions could be reached: (1) The association constant increases with the increase in the alkyl chain length. (2) For the salts (2b-5b), both in neutral and in acidic solutions, the binding constants increase as the number of CH(2) units increases. (3) The association constants of the complexes of the diaminoalkane salts and alpha-CD are lower than those of the corresponding neutral diaminoalkanes. (4) This difference between the binding constants of the diaminoalkanes and their respective salts decreases as the chain length increases. (5) By examining the effects of temperature on the (1)H NMR spectra, it was found that after addition of DCl the energy barrier for the threading-dethreading process of the salt of 5a is larger than that for the salt of 4a.     

Cationic and Neutral Rotaxanes Having Different Functional Groups in the Axle Molecule and Their Coordination to PtII

Dibenzo[24]crown‐8 (DB24C8) forms rotaxanes with a linear molecule having a dialkylammonium group and a triazole group as well as with the acetylation product of a cationic axle molecule. The former cationic rotaxane is stabilized by multiple intermolecular hydrogen bonds between the NH₂⁺ and oxyethylene groups. The neutral rotaxane contains the macrocycle in the vicinity of the terminal aryl group. The co‐conformation of both the cationic and neutral rotaxanes can be fixed by coordination of the triazole group of the axle molecule to PtCl₂(dmso)₂. A ¹H NMR spectroscopic study on the thermodynamics of the Pt coordination revealed a larger association constant for the rotaxanes than for the corresponding axle molecules and a larger value for the neutral rotaxane than for the cationic rotaxane.     

Synthesis and characterization of bis-[1]rotaxanes via salen-bridged bis-pillar[5]arenes

The series of salen-bridged bis-pillar[1]arenes were conveniently prepared by condensation reaction of5,5'-methylenebis(2-hydroxybenzalde hyde)or 5,5'-(propane-2,2-diyl)bis(2-hydroxybenzaldehyde)with mono-amido-functionalized pillar[5]arenes containing different terminal aminoalkyl groups in refluxing ethanol.The^1H NMR and 2D-NOESY spectra indicated that the salen-bridged bis-pillar[5]arenes with longer allcylene linker(n=3,4,6)formed the fascinating bis-[1]rotaxanes,while the salenbridged bis-pillar[5]arenes with short hydrazine and ethylenediamino linker(n=0,2)predominately existed in free form.The single crystal structure of the bis-pillar[5]are ne ambiguously indicated that two propylenediamino linker inserted in to two cavities of pillar[5]arene to form a novel bis-[1]rotaxanes.     

Self-assembly of novel [3]- and [2]rotaxanes with two different ring components: donor-acceptor and hydrogen bonding interactions and molecular-shuttling behavior

Three of the first kind of hetero[3]rotaxanes, which comprise one linear component and one neutral and one tetracationic ring component, have been assembled by using the intermolecular hydrogen bonding and donor-acceptor interactions. Three neutral [2]rotaxanes and three tetracationic [2]rotaxanes have also been synthesized as intermediate products or for the sake of property comparison. The linear molecules are incorporated with two glycine subunits, for templating the formation of the neutral tetraamide cyclophane, and one or two hydroquinone subunits, for inducing the formation of the tetracationic cyclophane. Variable-temperature (1)H NMR investigation reveals that the shuttling behavior of the tetracationic ring component along the linear component is substantially influenced by the existence of the neutral ring component. The spatial repelling interaction of the neutral ring on the electron-deficient tetracationic ring simultaneously weakens the latter's "positioning" tendency at both electron-rich hydroquinone sites of the linear component. As a result, the activation energy associated with the shuttling process of the tetracationic ring between the two hydroquinone sites is remarkably reduced in comparison to that of the shuttling process of the corresponding neutral ring-free [2]rotaxanes. For the first time, the rotation of the dipyridinium subunit around the axis formed by the two methylene groups connecting them within the tetracationic cyclophane has been investigated by variable-temperature (1)H NMR spectroscopy and the associated kinetic data have also been successfully obtained. Furthermore, the UV-vis and fluorescent properties of the new [2]- and [3]rotaxanes have been studied. The results demonstrate that [3]rotaxanes with different ring components possess unique kinetic features that are not available in [3]rotaxanes with identical ring components.     

Quantitative comparison of kinetic stabilities of metallomacrocycle-based rotaxanes

Four mononuclear metallomacrocycles with identical cavities but different transition metals (Os(VI), Pd(II), Pt(II), and Re(I)) were prepared. With these metallomacrocycles, the corresponding rotaxanes 2-Os, 2-Pd, 2-Pt, and 2-Re were self-assembled by hydrogen-bonding interactions. The kinetic stabilities of the rotaxanes were determined quantitatively and compared with each other by (1)H NMR spectroscopic techniques, including two-dimensional exchange spectroscopy (2D-EXSY) experiments. The activation free energies (DeltaG( not equal )) for the exchange between the rotaxanes 2-Os, 2-Pd and 2-Pt and their free components were determined to be 15.5, 16.0, and 16.4 kcal mol(-1), respectively. These magnitudes imply that the rotaxanes 2-Os, 2-Pd and 2-Pt are kinetically labile at room temperature and exist only as equilibrium mixtures with free components in solution. In contrast, the rotaxane 2-Re is kinetically stable enough to be isolated in pure form by silica gel chromatography under ordinary laboratory conditions. However, at higher temperatures (>60 degrees C) 2-Re was slowly disassembled into its components until the equilibrium was established. The rate constants were measured at three different temperatures, and the Eyring plot yielded the activation enthalpy DeltaH(not equal)=35 kcal mol(-1) and the activation entropy DeltaS(not equal)=27 eu for the disassembly of the rotaxane 2-Re in Cl(2)CDCDCl(2). These thermodynamic parameters gave the activation free energy DeltaG(not equal)(off)=27.1 kcal mol(-1) at 25 degrees C. Consequently, 2-Re is one example of a novel metallomacrocycle-based rotaxane that contains a coordination bond with enough strength to allow both for isolation in pure form around room temperature and for self-assembly at higher temperatures.     

Increased Halide Recognition Strength by Enhanced Intercomponent Preorganisation in Triazolium Containing [2]Rotaxanes

Three triazolium‐based [2]rotaxanes containing different sized axle and macrocycle components were synthesised in good yields (40–57 %) through chloride anion templation. The anion recognition properties of the interlocked receptor systems were investigated using ¹H NMR titration experiments: all three rotaxanes display impressive selectivities for halide anions over the more basic oxoanion acetate. The rotaxanes incorporating shorter, more rigid axle components with aryl‐substituted triazolium groups display substantially higher anion binding affinities than those with longer, bis‐alkyl‐substituted heterocycles, which is attributed to the increased intercomponent preorganisation afforded by the smaller axle component. Computational DFT and molecular dynamics simulations composed of unconstrained and umbrella sampling simulations corroborate the experimental observations.     

Cyclodextrin‐Based Size‐Complementary [3]Rotaxanes: Selective Synthesis and Specific Dissociation

α‐Cyclodextrin (CD)‐based size‐complementary [3]rotaxanes with alkylene axles were prepared in one‐pot by end‐capping reactions with aryl isocyanates in water. The selective formation of [3]rotaxane with a head‐to‐head regularity was indicated by the X‐ray structural analyses. Thermal degradation of the [3]rotaxanes bearing appropriate end groups proceeded by stepwise dissociation to yield not only the original components but also [2]rotaxanes. From the kinetic profiles of the deslippage, it turned out that the maximum yield of [2]rotaxane was estimated to be 94 %. Thermodynamic studies and NOESY analyses of such rotaxanes revealed that [2]rotaxanes are specially stabilized, and that the dissociation capability of the [3]rotaxanes to the components can be adjusted by controlling the structure of the end groups, direction of the CD groups, and length of the alkylene axle.