Optically sensed, molecular shuttles driven by acid-base chemistry

A pair of bistable [2]rotaxane, molecular shuttles were prepared that combine 1,2-bis(pyridinium)ethane and benzylanilinium recognition sites; acid-base controlled shuttling of DB24C8 was accompanied by a change in colour and/or fluorescence intensity.     

2]pseudorotaxane formation with N-benzylanilinium axles and 24-crown-8 ether wheels

[reaction: see text] As a hybrid of the N,N-dibenzylammonium and 1,2-bis(pyridinium)ethane axles, various N-benzylanilinium cations were investigated as suitable axles for the formation of [2]pseudorotaxanes with the 24-membered crown ethers 24C8 and DB24C8. The effect of electron-donating OCH(3) and electron-withdrawing CF(3) groups on both the anilinium and benzyl aromatic rings was studied. Formation constants and structural details were compared to the [2]pseudorotaxanes formed by the two aforementioned dibenzylammonium and 1,2-bis(pyridinium)ethane axles.     

Four‐State Molecular Shuttling of [2]Rotaxanes in Response to Acid/Base and Alkali‐Metal Cation Stimuli

In this study, we synthesized [2]rotaxanes possessing three recognition sites—a dialkylammonium, an alkylarylamine, and a tetra(ethylene glycol) stations—in their dumbbell‐like axle component and dibenzo[24]crown‐8 (DB24C8) as their macrocyclic component. These [2]rotaxanes behaved as four‐state molecular shuttles: i) under acidic conditions, the DB24C8 unit encircled both the dialkylammonium and alkylarylammonium stations; ii) under neutral conditions, the dialkylammonium unit was the predominant station for the DB24C8 component; iii) under basic conditions, when both ammonium centers were deprotonated, the alkylarylamine unit became a suitable station for the DB24C8 component; and iv) under basic conditions in the presence of an alkali‐metal cation, the tetra(ethylene glycol) unit recognized the DB24C8 component through cooperative binding of the alkali‐metal ion. In addition, we observed that the [2]rotaxanes exhibited selective recognition for metal cations. These shuttling motions of the macrocyclic component proceeded reversibly.     

Construction of a pH-driven supramolecular nanovalve

[Structure: see text] The versatility of supramolecular chemistry has been exploited in constructing nanovalves based on mesoporous silica MCM-41 and the mutual recognition between secondary dialkylammonium ions and dibenzo[24]crown-8 (DB24C8). Naphthalene-containing dialkylammonium threads were tethered to the MCM-41, followed by loading with coumarin 460 and capping with DB24C8. Controlled release of coumarin 460 from the pores of MCM-41 was demonstrated using different bases. The rate of release of coumarin 460 from the nanovalves depends on the size of the base.     

Metal-organic rotaxane frameworks; MORFs

Linear exodentate pyridinium ligands such as 1,2-bis(4,4'-bipyridinium)ethane or its bis N-oxide derivative can be used as axles for the formation of [2]pseudorotaxanes utilising 24-membered crown ethers such as dibenzo-24-crown-8 ether (DB24C8) as the wheel. These [2]pseudorotaxanes can be used to construct coordination networks using transition or lanthanide metal ions as the connecting nodes. 1-, 2- and 3D metal-organic rotaxane frameworks (MORFs) are possible. The resulting materials contain mechanically interlocked units and may be the forerunners of unique solids which contain machine-like components in an ordered array.     

Branched [n]rotaxanes (n = 2-4) from multiple dibenzo-24-crown-8 ether wheels and 1,2-bis(4,4'-dipyridinium)ethane axles

To investigate the possibility of incorporating the 1,2-bis(pyridinium)ethane[subset or is implied by]24C8 [2]pseudorotaxane motif into dendrimer like macromolecules, a series of branched [n]rotaxanes were prepared employing multiple dibenzo-24-membered crown ether wheels with various aromatic core structures and the 1,2-bis(4,4'-dipyridinium)ethane axle. Yields of branched [2]-, [3]- and [4]rotaxanes were dependent on the size of the core and the relative proximity of the crown ethers arranged around the core unit.     

Molecular shuttles by the protecting group approach

Two new [2]rotaxane-based molecular shuttles, in which a mechanically bound dibenzo[24]crown-8 (DB24C8) macroring shunts back and forth between two dialkylammonium recognition sites situated on a chemical dumbbell, have been constructed by a novel synthetic strategy that relies upon the use of the tert-butoxycarbonyl (Boc) protecting group. During the syntheses of both molecular shuttles, this protecting group masks a dialkylammonium recognition center which is liberated only after the [2]rotaxane constitution is established. In both cases, the molecular shuttles' other dialkylammonium center is essential for the rotaxane-forming reactions and it ensures that DB24C8 is interpenetrated by threadlike precursors, as a result of noncovalent bonding interactions, to produce [2]pseudorotaxanes which are stoppered subsequently through 1,3-dipolar cycloadditions between azides and bulky acetylenedicarboxylates. The new molecular shuttles have been examined by means of dynamic 1H NMR spectroscopy, which reveals that the movements of the DB24C8 macroring are very highly dependent both on solvent properties and on the nature of the spacer unit linking the two dialkylammonium centers. Thus, DB24C8 shunts facilely between the dialkylammonium centers when the shuttles are dissolved in solvents that readily donate their nonbonding electrons into noncovalent bonds, e.g., DMF, and when spacer units that do not offer much steric resistance to shuttling, e.g., hexamethylene, are used. On the other hand, shuttling is difficult in solvents that are less inclined to donate their electrons into noncovalent bonds, e.g., (CDCl2)2, and when relatively bulky benzenoid spacer units, e.g., p-xylylene, link the two dialkylammonium centers. It has been proposed that the DB24C8 might act as a "ferry" which carries a proton between dialkylammonium and dialkylamine moieties in a singly protonated [2]rotaxane by means of ion-dipole interactions.     

Reversible Mechanical Switching of Magnetic Interactions in a Molecular Shuttle

An acid–base switchable molecular shuttle based on a [2]rotaxane, incorporating stable radical units in both the ring and dumbbell components, is reported. The [2]rotaxane comprises a dibenzo[24]crown-8 ring (DB24C8) interlocked with a dumbbell component that possesses a dialkylammonium (NH₂⁺) and a 4,4′-bipyridinium (BPY²⁺) recognition site. Deprotonation of the rotaxane NH₂⁺ centers effects a quantitative displacement of the DB24C8 macroring to the BPY²⁺ recognition site, a process that can be reversed by acid treatment. Interaction between stable 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals connected to the ring and dumbbell components could be switched between noncoupled (three-line electron paramagnetic resonance (EPR) spectrum) and coupled (five-line EPR spectrum) upon displacement of the spin-labelled DB24C8 macroring. The complete base- and acid-induced switching cycle of the EPR pattern was repeated six times without an appreciable loss of signal, highlighting the reversibility of the process. Hence, this molecular machine is capable of switching on/off magnetic interactions by chemically driven reversible mechanical effects. A system of this kind represents an initial step towards a new generation of nanoscale magnetic switches that may be of interest for a variety of applications.     

Template-directed synthesis of kinetically and thermodynamically stable molecular necklace using ring closing metathesis

We report the template-directed synthesis of a well-defined, kinetically stable [5]molecular necklace with dialkylammonium ion (R(2)NH(2)(+)) as recognition site and DB24C8 as macrocycle. A thread containing four dialkylammonium ions with olefin at both ends was first synthesized and then subjected to threading with an excess amount of DB24C8 to form pseudo[5]rotaxane, which in situ undergoes ring closing metathesis at the termini with second generation Grubbs catalyst to yield the desired [5]molecular necklace. The successful synthesis of [5]molecular necklace is mainly attributed to the self-assembly and dynamic covalent chemistry which allows the formation of thermodynamically most stable product. The self-assembly of the DB24C8 ring onto the recognition site known as templating effect was driven by noncovalent stabilizing interactions like [N(+)-H···O], [C-H···O] hydrogen bonds as well as [π···π] interactions which is facilitated in non-polar solvents. The reversible nature of olefin metathesis reaction makes it suitable for dynamic covalent chemistry since proof-reading and error-checking operates until it generates thermodynamically the most stable interlocked molecule. Riding on the success of [5]molecular necklace, we went a step further and attempted to synthesize [7]molecular necklace using the same protocol. This led to the synthesis of another thread with olefin at both ends but having six dibenzylammonium ions along the thread. However, the extremely poor solubility of this thread containing six secondary ammonium ions limits the self-assembly process even after we replaced the typical PF(6)(-) counter anion with a more lipophilic BPh(4)(-) anion. Although the poor solubility of the thread remains the bottleneck for making higher order molecular necklaces yet this approach of "threading-followed-by-ring-closing-metathesis" for the first time produces kinetically and thermodynamically stable, well-defined, homogeneous molecular necklace which was well characterized by one-dimensional, two-dimensional, variable temperature proton NMR spectroscopy and ESI mass spectroscopy.     

A mechanical "flip-switch". Interconversion between co-conformations of a [2]rotaxane with a single recognition site

[2]Rotaxanes utilising the 1,2-bis(pyridinium)ethane, 24-crown-8 motif can exist in two distinct co-conformations whose relative abundances are solvent dependent.     

A New Motif for the Self-Assembly of [2]Pseudorotaxanes; 1,2-Bis(pyridinium)ethane Axles and [24]Crown-8 Ether Wheels

Multiple intramolecular interactions help to stabilize the novel [2]pseudorotaxanes formed from 1,2-bis(pyridinium)ethane dications (which act as axles) and 24-membered crown ethers (which act as wheels; see structure). This is the first successful sythesis of [2]pseudorotaxanes with [24]crown-8 as the macrocycle.     

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.     

Characterization of a slippage stopper for the 1,2-bis(pyridinium)ethane-[24]crown-8 ether [2]pseudorotaxane motif

Comparison of 1,2-bis(pyridinium)ethane axles containing iso-nicotinate esters (R=ethyl, iso-propyl, cyclohexyl, cycloheptyl) as the pyridinium unit shows that the cyclohexyl group provides a stopper size that allows slippage to be used as a method for pseudorotaxane/rotaxane formation employing dibenzo-24-crown-8 ether (DB24C8) as the wheel. Rates of complexation and decomplexation were measured in a number of solvent systems and the kinetic and thermodynamic parameters associated with the process reported.     

A molecular plug-socket connector

A monocationic plug-socket connector that is composed, at the molecular level, of three components, (1) a secondary dialkylammonium center (CH2NH2+CH2), which can play the role of a plug toward dibenzo[24]crown-8 (DB24C8), (2) a rigid and conducting biphenyl spacer, and (3) 1,4-benzo-1,5-naphtho[36]crown-10 (BN36C10), capable of playing the role of a socket toward a 4,4'-bipyridinium dicationic plug, was synthesized and displays the ability to act as a plug-socket connector. The fluorescent signal changes associated with the 1,5-dioxynaphthalene unit of its BN36C10 portion were monitored to investigate the association of this plug-socket connector with the complementary socket and plug compounds. The results indicate that (1) the CH2NH2+CH2 part of the molecular connector can thread DB24C8 in a trivial manner and (2) the BN36C10 ring of the connector can be threaded by a 1,1'-dioctyl-4,4'-bipyridinium ion only after the CH2NH2+CH2 site is occupied by a DB24C8 ring. The two connections of the three-component assembly are shown to be controlled reversibly by acid/base and red/ox external inputs, respectively. The results obtained represent a key step for the design and construction of a self-assembling supramolecular system in which the molecular electron source can be connected to the molecular electron drain by a molecular elongation cable.     

Probing polyvalency in artificial systems exhibiting molecular recognition

An approach to the study of polyvalency-the interaction of polyvalent receptors with polyvalent ligands-in unnatural systems is outlined. In this study, the complexation of dibenzylammonium cations by dibenzo[24]crown-8 or benzometaphenylene[25]crown-8 is utilized as the component receptor-ligand interaction. Two analogous multivalent receptors-each containing either seven dibenzo[24]crown-8 (DB24C8 CLUSTER) or seven benzometaphenylene[25]crown-8 (BMP25C8 CLUSTER) moieties appended to a modified beta-cyclodextrin core-were prepared in moderate yields. For each of these multivalent receptors, complementary mono- and divalent ligands containing one or two dialkylammonium centers, respectively, were prepared in good yields. These ligands contained fluorine atom substituents to allow their interactions with crown ether compounds to be probed by (19)F NMR spectroscopy. The complexation of these monovalent ligands with the DB24C8 CLUSTER and the BMP25C8 CLUSTER was studied by determining the average binding constant (K(AVE)) between the receptors and ligands. The abilities of the crown ether clusters to complex with these monovalent ligands was compared with those of the monovalent crown ethers dibenzo[24]crown-8 and benzometaphenylene[25]crown-8. In both instances, it was found that clustering seven crown ethers together into one molecule is detrimental to the abilities of the crown ether moieties to complex with monovalent dialkylammonium ligands. The complexation of the divalent ligands by the DB24C8 CLUSTER and the BMP25C8 CLUSTER was then studied-again by determining K(AVE)-and their abilities to complex with these ligands was compared with those of their respective component interactions. By determining K(AVE) for the polyvalent interaction, it was possible to calculate an association constant, K(POLY), for the binding of the divalent ligands by the DB24C8 CLUSTER and the BMP25C8 CLUSTER compounds. In both instances K(POLY) for the polyvalent interaction was found to be approximately 2 orders of magnitude higher than the association constants, K(A), for the component interaction.     

Toward interlocked molecules beyond catenanes and rotaxanes

A linear bis secondary dialkylammonium ion-containing scaffold-based upon an anthracenyl core-has been synthesized. It has been demonstrated that it is possible to dock either one or two dibenzo[24]crown-8 (DB24C8) macrocycles onto this scaffold to afford either a [2]- or [3]pseudorotaxane, respectively. In solution, the association constants for the formation of each of these species has been quantified by employing (1)H NMR spectroscopy, and both species survive in the "gas phase" as evidenced by FAB mass spectrometry. Additionally, the X-ray crystal superstructure of the [3]pseudorotaxane has been determined.     

Controlling the ON/OFF threading of a terpyridine containing [2]pseudorotaxane ligand via changes in coordination geometry

A 1,2-bis(pyridinium)ethane type axle containing a terpyridine chelate group, when combined with 24-membered crown ethers, forms [2]pseudorotaxanes, the stability of which can be controlled by coordination of metal ions with different geometries.     

Binding of secondary dialkylammonium salts by pyrido-21-crown-7

Pyrido-21-crown-7 (P21C7) has been synthesized and shown to form [2]pseudorotaxanes spontaneously with secondary dialkylammonium ions. These complexes are stronger than their benzo-21-crown-7 counterparts and much stronger than their dibenzo-24-crown-8 counterparts. Based on this new P21C7/secondary dialkylammonium salt recognition motif, a [2]rotaxane terminated by phenyl groups as stoppers has been successfully constructed using the threading-followed-by-stoppering technique.     

Chemical and electrochemical formation of pseudorotaxanes composed of alkyl(ferrocenylmethyl)ammmonium and dibenzo[24]crown-8

Protonation of p-xylylaminomethylferrocene (1) and n-hexylaminomethylferrocene (2) by HCl and NH(4)PF(6) forms the ferrocenylmethyl(alkyl)ammonium salt. Inclusion of the compounds by dibenzo[24]crown-8 (DB24C8) produces [2]pseudorotaxanes, [(DB24C8)(1-H)](+)(PF(6)) and [(DB24C8)(2-H)](+)(PF(6)), respectively. X-ray diffraction of the former product indicates an interlocked structure composed of the axis and the macrocyclic molecule. Intermolecular N-H...O and C-H...O interactions and stacking of the aromatic planes are observed. [(DB24C8)(1-H)](+)(PF(6)), in the solid state, is characterized by IR spectroscopy and elemental analyses. A similar reaction of 1,1'-bis(p-xylylaminomethyl)ferrocene (3) forms a mixture of [2] and [3]pseudorotaxanes, [(DB24C8)(3-H(2))](2+)(PF(6))(2) and [(DB24C8)(2)(3-H(2))](2+)(PF(6))(2). The latter product having two DB24C8 molecules is isolated and characterized by X-ray crystallography. Formation of these pseudorotaxanes in a CD(3)CN solution is evidenced by (1)H NMR and mass spectrometry. Electrochemical oxidation of 1-3 at 0.4 V (vs Ag(+)/Ag) in the presence of TEMPOH (1-hydroxy-2,2,6,6-tetramethylpiperidine) and DB24C8 affords the corresponding pseudorotaxanes. The ESR spectrum of the reaction mixture indicates the formation of a TEMPO radical in high yield. Details of the conversion of the dialkylamino group of the ligand to the dialkylammonium group are investigated by using a flow electrolysis method linked to spectroscopic measurements. The proposed mechanism for the reaction involves the ferrocenium species, formed by initial oxidation, which undergoes electron transfer from nitrogen to the Fe(III) center, producing a cation radical at the nitrogen. Transfer of hydrogen from TEMPOH to the cation radical and inclusion of the resulting dialkylammonium species by DB24C8 yields the pseudorotaxanes.     

The influence of macrocyclic polyether constitution upon ammonium ion/crown ether recognition processes

Secondary dialkylammonium (R2NH2+) ions are bound readily by dibenzo[24]crown-8 (DB24C8) to form threaded complexes, namely [2]pseudo-rotaxanes. The effect of replacing one or both of the catechol rings in DB24C8 with resorcinol rings upon the crown ether's ability to bind R2NH2+ ions has now been investigated. When only one aromatic ring is changed from catechol to resorcinol, a crown ether with a [25]crown-8 constitution is created-namely benzometaphenylene[25]crown-8 (BMP25C8). A [2]pseudorotaxane is formed in the solid state when BMP25C8 is co-crystallized with dibenzylammonium hexafluorophosphate, as evidenced by its X-ray crystal structure. Furthermore, this crown ether has been shown to bind R2NH2+ ions in solution, an observation which has been exploited in the synthesis of the first BMP25C8-containing [2]rotaxane. The methodology employed to generate this [2]rotaxane--the reaction of an amine with an isocyanate to form a urea--was tested initially on a system incorporating DB24C8 and was shown to work efficiently. Both [2]rotaxanes have been fully characterized by 1H and 13C NMR spectroscopies, FAB mass spectrometry and X-ray crystallography. Interestingly, the unsymmetrical nature of the dumbbell-shaped component in each of the two [2]rotaxanes renders each face of the encircling macrocyclic polyether diastereotopic, a feature that is apparent upon inspection of their 1H NMR spectra. The resonances associated with the diastereotopic protons on each face of the macrorings are well enough resolved to enable the faces of the crown ethers to be readily identified with respect to their protons by 1H NMR spectroscopy. Unambiguous assignments can be made as a result of the fact that the protons on each face of the macrocyclic polyether experience a unique set of through-space interactions, as evidenced by T-ROESY experiments. Additionally, the two-dimensional NMR analyses are in agreement with the X-ray crystallographic studies performed on these [2]rotaxanes, indicating that the crown ethers are located intimately around the NH2+ centers as expected. Replacement of both catechol rings in the DB24C8 constitution with resorcinol rings results in a crown ether with a [26]crown-8 constitution--namely bismetaphenylene[26]crown-8 (BMP26CS). All the evidence to date points to the fact that this further change in constitution results in a crown ether that does not bind R2NH2+ ions in either the solution or solid states.