Sheng-Hsien Chiu

Acid/Base‐ and Anion‐Controllable Organogels Formed From a Urea‐Based Molecular Switch

Low-molecular-weight organogels have applications in several fields, including molecular sensing, nanostructure assembly, and drug delivery. Ideally, these materials would switch reversibly between their solution and gel states through the addition or removal of heat, electrons, or ions. Although these modes of operation are similar to those employed for switches based on interlocked molecules, organogels formed from pseudorotaxaneor rotaxane-type gelators are rare. Indeed, we are aware of only a few previously reported examples, all of which feature long alkyl chains or cholesterol units incorporated into the molecular structures to assist the gelation process. Predicting the molecular structures of potential gelators and their preferred solvents remains difficult, and developing new rotaxane-based gelators that do not feature commonly used types of gelation units (e.g., long alkyl chains, steroids) in their structures is particularly challenging. Herein we report the serendipitous discovery of a urea-based [2]rotaxane that behaves as both a molecular switch and an organogelator; both functions are mediated by acid/base and anion control. The reaction of the macrocycle 1, the amino-terminated salt [2-H][PF6], [7] and the isocyanate 3 in CH3NO2 gave the dumbbell-shaped salt [4-H][PF6] and the [2]rotaxane [5-H][PF6] in 49 and 46% yield, respectively (Scheme 1). The binding constant for the assembly formed from the macrocycle 1 and dibenzylammonium hexafluorophosphate ((DBA)PF6) in CD3NO2 is (300 30)m , and 1 interacts only negligibly with diphenylurea derivatives in this solvent. 8] Therefore we suspected that the interlocked macrocycle in the [2]rotaxane [5-H][PF6] would prefer to encircle the DBA station, rather than the diphenylurea station, when dissolved in CD3NO2. Indeed, the 2D NOESY spectrum of the [2]rotaxane [5-H][PF6] in CD3NO2 shows cross-signals between the ethylene glycol protons of the macrocyclic unit and the aromatic protons of the 3,5-di-tert-butylphenyl stopper adjacent to the DBA center, however, no crosssignals are seen between the macrocyle and the stopper unit adjacent to the urea station. As expected, addition of potassium tert-butoxide (1 equivalent) to a solution of the [2]rotaxane [5-H][PF6] (CD3NO2, 13.6 mm) resulted in significant shifts in the locations of many of the signals in the H NMR spectrum (Figure 1). The significant downfield shift of the signal for the macrocyle NH protons, and the appearance of signals for the formerly severely broadened urea protons suggested the formation of hydrogen bonds to the carbonyl group of the urea station (Figure 1b). The addition of perchloric acid (70% in H2O, 1 equivalent) to this solution afforded a spectrum similar to that of the original [2]rotaxane. These observations suggest that the [2]rotaxane [5-H][X] is an acid/base-controllable molecular switch; the interlocked macrocyclic unit can be Scheme 1. Synthesis and switching of the [2]rotaxane [5-H][PF6].

A Molecular Cage-Based [2]Rotaxane That Behaves as a Molecular Muscle

We report a molecular cage-based [2]rotaxane that functions as an artificial molecular muscle through the control of the addition and removal of fluoride anions. The percentage change in molecular length of the [2]rotaxane is about 36% between the stretched and contracted states, which is larger than the percentage change (approximately 27%) in human muscle.

Direct observation of mixed-valence and radical cation dimer states of tetrathiafulvalene in solution at room temperature: association and dissociation of molecular clip dimers under oxidative control.

We have observed the mixed-valence and radical cation dimer states of a glycoluril-based molecular clip with tetrathiafulvalene (TTF) sidewalls at low concentration (1 mM) at room temperature. This molecular clip has four consecutive anodic steps in its cyclic voltammogram, which suggests a sequential oxidation of these TTF sidewalls to generate species existing in several distinct charge states: neutral monomers, mixed-valence dimers, radical cation dimers, and fully oxidized tetracationic monomers. The observation of characteristic NIR spectroscopic absorption bands at approximately 1650 and 830 nm in spectroelectrochemistry experiments supports the presence of intermediary mixed-valence and radical cation dimers, respectively, during the oxidation process. The stacking of four TTF radical cations in the dimer led to the appearance of a charge-transfer band at approximately 946 nm. Nanoelectrospray ionization mass spectrometry was used to verify the tricationic state and confirm the existence of other different charged dimers during the oxidation of the molecular clip.

Solvent‐Free Synthesis of the Smallest Rotaxane Prepared to Date

[2]Rotaxanes—supermolecules comprising interlocked macrocyclic and dumbbell-shaped components—are fascinating materials for the construction of molecular devices because of the machinelike movement of their constituent parts. The development of efficient, convenient, and environmentally friendly methods for the synthesis of these functional interlocked molecules has progressed tremendously in the past decade. We became interested, however, in answering the following fundamental question: What is the smallest [2]rotaxane that can be synthesized, either in terms of molecular weight or the number of constituent atoms? We identified the crown ether/secondary dialkylammonium ion pair, which can be simplified into a few repeating CH2CH2O units that encircle a threadlike component as small as a dimethylammonium (CH3NH2 CH3) ion, as the simplest and smallest recognition system for preparing [2]rotaxanes. Herein, we report a new and efficient solvent-free reaction which involves ball-milling of the [2]pseudorotaxane formed from dipropargylammonium tetrafluoroborate and the crown ether [21]crown-7 (21C7) on SiO2 with 1,2,4,5-tetrazine. This led to the isolation in high yield (81 %) of the smallest [2]rotaxane reported to date (Scheme 1). Although it has been postulated for some time that macrocycles possessing 21 or more atoms in their ring will be able to accommodate an alkyl chain, it was only recently reported that a secondary dialkylammonium ion could be threaded through a 21-membered ring macrocycle, namely benzo[21]crown-7 (B21C7). In addition, a phenyl group can act as the stopper that prevents the unthreading of the interlocked ring-shaped and linear components when this small macrocycle is used. We proposed that Diels–Alder reactions of 1,2,4,5-tetrazine with the terminal alkyne units of a 21C7-based [2]pseudorotaxane would produce pyridazine end groups, which are slightly less bulky than phenyl groups, and might also function as stoppers in a 21C7-containing [2]rotaxane. We chose the dipropargylammonium ion (1-H) as the alkyne-terminated linear component in the small [2]pseudorotaxane precursor, expecting its small CH2NH2 CH2 unit to reside within the cavity of the crown ether 21C7, stabilized through N H···O and C H···O hydrogen bonds. The alkyne termini are available for functionalization (Scheme 1) through Diels–Alder reactions with 1,2,4,5-tetrazine to generate small, but nevertheless sufficiently bulky, pyridazine rings for stoppering the pseudorotaxanes under solvent-free conditions. The H NMR spectrum (Figure 1b) of an equimolar (5 mm) mixture of 21C7 and 1-H·BF4 in CD3CN at room temperature shows the chemical shifts of the protons of the complex are significantly different from those of its free components. The appearance of broad signals for both the free and complexed thread 1-H·BF4 in the H NMR spectrum (Figure 1c) of a 1:2 molar ratio mixture of 21C7 and 1-H·BF4 in CD3CN suggested that the rates of exchange during the complexation and decomplexation processes were slow on the H NMR spectroscopic timescale at 400 MHz under these conditions, but not sufficiently slow to provide the sharp signals required to obtain an accurate value for the association constant through the single-point method. Instead, we used isothermal titration calorimetry (ITC) to determine an association constant of (14 00

A guanidinium ion-based anion- and solvent polarity-controllable molecular switch.

The macrocycle bis-p-xylyl[26]crown-6 (BPX26C6) is capable of complexing guanidinium ions in a [2]pseudorotaxane-like manner in solution. A corresponding molecular switch can be operated through changes in solvent polarity or the addition and removal of halogen and acetate anions.

Efficient Solvent-Free Syntheses of [2]-and [4]Rotaxanes

Rotaxanes have potential applicability as molecular actuators and switches within mesoscale molecular electronic devices. Among the protocols devised for preparing rotaxanes, threading followed by stoppering has attracted the most attention. Nevertheless, synthesizing rotaxanes in high yields by this approach can be challenging because several factors affect the formation of the precursor pseudorotaxanes in solution—for example, low association constants for the interactions between the threadand beadlike components, the use of competing solvents and/or elevated temperatures, and the formation of interfering by-products during the stoppering process. Although solvent-free conditions would, in theory, minimize the degree of dissociation of the pseudorotaxane complexes during the stoppering reaction and allow high-order rotaxanes to be generated more efficiently, a new challenge arises in choosing a suitable stoppering reaction that can be performed by grinding a wellmixed solid phase. To the best of our knowledge, only two types of rotaxanes have been synthesized through solid-tosolid grinding: one through the reaction of a mixture of bis-pphenylene[34]crown-10, a benzyl bromide derivative incorporating a bipyridinium recognition site, and a pyridinecontaining stopper, and the other through ball-milling of polypseudorotaxane complexes—comprising a-cyclodextrin and poly(tetrahydrofuran) components—with isocyanate stoppers. Both of these cases gave low-to-moderate yields of their desired products (< 45%), thus suggesting that these reactions are not suitable for the efficient syntheses of higherorder rotaxanes. Herein, we report a new solid-state ballmilling reaction that produces both [2]and [4]rotaxanes efficiently and in high yield. The formation of imines through the dehydration of aldehydes and primary amines can be achieved in high yield by solid-state ball-milling. As imines are in general easily hydrolyzed, we were not inclined to use this condensation reaction to construct higher-order rotaxanes. Instead, we turned our attention toward the formation of hexahydropyrimidines by condensing carbonyl compounds with 1,3-diamines. We chose 1,8-diaminonaphthalene (3) as a suitable diamine for the reaction with a threadlike moiety terminated with a formyl group because of its steric bulk and the stability of the resulting dihydropyrimidine stopper units. Previously, we reported that the oxygen-deficient macrocycle 1 forms a complex with a dibenzylammonium (DBA) ion in CD3CN (Ka = 200m ). Thus, as the first step toward preparing a [2]rotaxane under solvent-free conditions from such components, we concentrated an equimolar mixture of the macrocycle 1 and the dialdehyde 2-H·PF6 in CH3CN under reduced pressure to afford a white solid, which we assumed to contain predominantly the [2]pseudorotaxane complex [1·2-H][PF6] (Scheme 1). After dissolving portions of the solids in CD3CN, we used H NMR spectroscopy to monitor the ball-milling reaction of a 1:2 mixture of the [2]pseudorotaxane complex [1·2-H][PF6] and 1,8-diaminonaphthalene at ambient temperature. A new set of signals appeared with increasing intensity over time (Figure 1). After 1 h, these signals were predominant (Figure 1e), so we subjected the mixture to column chromatography and isolated the [2]rotaxane 4-H·PF6 in 80% yield. [11] The yield increased to 87% when we increased the ratio of the macrocycle 1 and the dialdehyde thread 2-H·PF6 in the solid mixture to 1.2:1. The solution reaction of 1, 2-H·PF6, and diamine 3 (50:50:100 mm) in CH3CN did not proceed as efficiently as it did through ball-milling: traces of 2-H·PF6 remained detectable by TLC after 24 h. The use of H NMR spectroscopy to monitor a slightly more dilute mixture (20:20:40 mm) in CD3CN indicated that the reaction was complete after 24 h, and provided the [2]rotaxane 4-H·PF6 in 48% yield. When we mixed 1, 2-H·PF6, and 3 as solids in a 1:1:2 ratio without first generating the solid [2]pseudorotaxane complex [1·2-H][PF6], the same ball-milling conditions afforded a mixture of the [2]rotaxane 4-H·PF6 and the dumbbell-like salt 5-H·PF6 (Figure 2b) in yields of 49 and 44%, respectively. To the best of our knowledge, this process is by far the most efficient synthesis of a rotaxane by direct grinding of the macrocyclic, threadlike, and stoppering components as independent solids. Although this result indicates that the threading of the macrocycle 1 around the threadlike dialdehyde 2-H·PF6 could occur during the grinding process, preforming the [2]pseudorotaxane [1·2-H][PF6] as a solid substantially increased the yield of the reaction. To prove that this solid-state rotaxane synthesis occurred through threading followed by stoppering, rather than by slippage, we dissolved the [2]rotaxane 4-H·PF6 in CD3SOCD3 and monitored its H NMR spectra at 323 K over time. We detected no signals of the free components in the H NMR spectrum recorded after 3 h, which suggests that [*] S.-Y. Hsueh, K.-W. Cheng, Prof. S.-H. Chiu Department of Chemistry, National Taiwan University No. 1, Sec. 4, Roosevelt Road, Taipei (Taiwan, ROC) Fax: (+886)2-3366-1677 E-mail: shchiu@ntu.edu.tw Homepage: http://www.ch.ntu.edu.tw/english/efaculty/people/ chiu-eng.html

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.

Squaraine‐Based [2]Rotaxanes that Function as Visibly Active Molecular Switches

Molecular switches undergo reversible (co)conformational shifts or molecular transformations, under the influence of pH, photons, cations, anions, heat, and/or electrons, between two or more different stable states. Although many external stimuli (inputs) are available to operate molecular switches, the most important outputs are generally mechanical forces and optical signals: the former allows the construction of artificial molecular machines and the latter provides the possibility for molecular sensing. Thanks to burgeoning growth in the synthesis of interlocked molecules, several rotaxaneand catenane-based molecular switches have been developed in which detectable optical signals accompany the migration of interlocked macrocycles between different recognition sites; such materials are potentially useful for constructing complicated molecular logic and optical devices. Light-active molecular switches providing fluorescence outputs at long wavelengths, approaching the near-infrared (NIR) region, have potential practical importance in biomedicine and photodynamic therapy for sensing and signaling in living tissues and cells. Squaraine-based fluorescence dyes generally exhibit low quantum yields in polar solvents; in their host-encapsulated forms, however, they can experience less-polar local environments and, therefore, exhibit significantly increased quantum yields, even in polar solvents. This behavior suggests a straightforward approach toward the design of squaraine-based optical switches: if the solvent-exposed and encapsulated forms of a squaraine unit can be generated as two distinguishable stable states of a switchable rotaxane in a polar solvent, variations in the optical signals in the longwavelength-fluorescence region should be produced within each switching cycle. Herein, we report the synthesis and operation of squaraine-based optical molecular switches, which display striking changes in their fluorescence signals that are visible to the naked eye. Previously, we reported that the molecular cage 1 forms complexes with the squaraine derivatives 2 under the assistance of Na ions as templates. Thus, we anticipated that the [2]rotaxane[4-long·Na2]ACHTUNGTRENNUNG[4 ClO4] (Scheme 1) would function as a molecular switch in CD3CN if we could remove the templating Na ions and, thereby, move the molecular cage from the squaraine station to the bipyridinium one; this process should have the effect of decreasing the intensity of the long-wavelength-fluorescence emission of the [2]rotaxane.

A switchable macrocycle–clip complex that functions as a NOR logic gate

We have synthesized a new molecular switch-based on a macrocycle-clip complex-whose switching behavior not only can be controlled through the use of either K+-[2,2,2]cryptand or NH4+-Et3N systems but also provides color changes that are visible to the naked eye; consequently, this system operates as a two-input NOR functioning molecular logic gate.

Making molecular-necklaces from rotaxanes

Abstract During an attempt to synthesize polyrotaxanes by Wittig step-growth polymerization between a dibenzylic bis(triphenylphosphonium)-stoppered [2]rotaxane, with an NH2+ recognition site encircled by a DB24C8 ring, and appropriate derivatives of terephthaldehyde carrying bulky groups, large macrocyclic compounds with the topologies of catenanes and molecular-necklaces, are formed.