An Anion-Switchable Dual-Function Rotaxane Catalyst.

In situ switching of the associated anions of a rotaxane catalyst between Cl- and TFPB- exposes its dialkylammonium and imidazolium stations, respectively, thereby selectively catalyzing the reactions of a mixture of trans-cinnamaldehyde and an aliphatic thiol to yield the Michael adduct and the thioacetal product, respectively.

Improbable Rotaxanes Constructed From Surrogate Malonate Rotaxanes as Encircled Methylene Synthons.

We have developed a new approach for the synthesis of "improbable" rotaxanes by using malonate-centered rotaxanes as interlocked surrogate precursors. Here, the desired dumbbell-shaped structure can be assembled from two different, completely separate, portions, with the only residual structure introduced from the malonate surrogate being a methylene group. We have synthesized improbable [2]- and [3]rotaxanes with all-hydrocarbon dumbbell-shaped components to demonstrate the potential structural flexibility and scope of the guest species that can be interlocked when using this approach.

Complementarity of 2,6-Dimethanolpyridine and Di(ethylene glycol) in the Complexation of Na+ Ions: Attaching Multiple Copies of [2]Catenane Branches to Isophthalaldehyde-Containing Cores.

In this study we found that 2,6-dimethanolpyridine displays good complementarity toward di(ethylene glycol) for the complexation of Na+ ions, allowing us to use this recognition system for the efficient synthesis of hetero[2]catenanes; indeed, it allowed us to attach multiple copies of [2]catenanes to branched systems presenting multiple isophthalaldehyde units. When we attempted to form a catenane from a preformed macrocycle featuring only a single di(ethylene glycol) unit, reacting it with a di(ethylene glycol) derivative presenting two amino termini, isophthalaldehyde, and templating Na+ ions [i.e., with the aim of using di(ethylene glycol)·Na+·di(ethylene glycol) recognition to template the formation of the interlocked imino macrocycle], the yields of the hetero[2]catenane and homo[2]catenane, comprising two imino macrocyclic units, were both poor (14% and 7%, respectively). In contrast, when one or two 2,6-dimethanolpyridine units were present in the preformed macrocycles, their reactions with the same diamine, dialdehyde, and Na+ ions provided the hetero[2]catenanes with high selectivity and efficiency (44% and 64% yields, respectively), with minimal formation of the competing homo[2]catenane. The high complementary of the 2,6-dimethanolpyridine·Na+·di(ethylene glycol) ligand pair allowed us to synthesize [2]catenane dimers and trimers directly from corresponding isophthalaldehyde-presenting cores, with yields, after subsequent reduction and methylation, of 42% and 31%, respectively.

N-Heterocyclic Carbene Copper(I) Rotaxanes Mediate Sequential Click Ligations with All Reagents Premixed.

We have prepared NHC-CuI complexes with a rotaxane structure and used them as sterically sensitive catalysts for one-pot sequential copper-catalyzed azide/alkyne cycloadditions in solutions containing all of the coupling partners premixed in unprotected form. Most notably, a photolabile and sterically encumbered complex first catalyzed the coupling of a less bulky azide/alkyne pair; after removing the protective macrocyclic component from the rotaxane structure, through irradiation with light, the exposed dumbbell-shaped NHC-CuI complex catalyzed the second click reaction of a bulkier azide/alkyne pair. Using this approach, we obtained predominantly, from a single sealed pot, a bis-triazole product (84 %) from a mixture of two sterically distinct azides and a diyne.

Using Alkali Metal Ions To Template the Synthesis of Interlocked Molecules.

In 1987, Pedersen, Cram, and Lehn were awarded the Nobel Prize in Chemistry to honor their achievements in, among other things, the selective recognition of alkali metal ions by synthetic hosts. Almost three decades later, the 2016 Nobel Prize went to Stoddart, Sauvage, and Feringa for the development of artificial molecular machines, in which interlocked molecules play a significant role. Surprisingly, although many rotaxane- and catenane-based molecular machines have been constructed using various templating approaches, alkali metal ions, which are good templates for crown ether synthesis, have only rarely been applied as templates for the assembly of these interlocked molecules. This paucity of examples is probably due to the less well defined coordination numbers and geometries in the complexation of alkali metal ions to common oxygen-containing ligands, resulting in much weaker metal-ligand interactions and less predictable structures for their complexes compared with those formed between transition metal ions and common pyridine-containing ligands. Nevertheless, the ease of removing alkali metal ions from interlocked compounds and their much lower toxicity compared with that of transition metal ions are attractive features that have inspired their use as templates in the synthesis of interlocked molecules. About a decade ago, we began investigating the feasibility of using alkali metal ions to template the formation of catenanes and rotaxanes, with the hope of developing facile, broadly applicable, green, and efficient methods for their construction. We noticed that the interactions between oxygen-containing ligands and alkali metal ions can be strengthened by minimizing the effects of competing interactions from solvent molecules and counteranions. Thus, to increase the solubility of the metal ion salts in less polar solvents (e.g., CH2Cl2, CHCl3) and minimize ion pairing, we chose tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB), a weakly coordinating anion, as the counteranion for the alkali metal ions applied as templates. Our strategy has been based on the association of simple and general recognition units: (i) the orthogonal arrangement of two oligo(ethylene glycol) chains around an alkali metal ion and (ii) the encircling of a single urea/amide unit by an oligo(ethylene glycol)-containing macrocycle in the presence of a templating alkali metal ion. The former recognition system has allowed the facile construction of many interesting interlocked structures, including cyclic [2]catenane trimers and tetramers; the latter has provided several rotaxanes, including some incorporating monomers of practically important (macro)molecules (e.g., peptides, polymers) and some that behave as switches with unique functions (e.g., catalysis, gelation). The components in these recognition systems possess high flexibility in terms of their structures and the choice of suitable alkali metal ion templates. This Account tells the story of the concept behind this alkali metal ion-templating approach as well as its elaboration, scope, and recent advances. We hope to convince the reader that alkali metal ions are powerful templates for assembling interlocked structures and compounds and also to demonstrate the range of possibilities that they provide for future endeavors.

Interlocked Photo-degradable Macrocycles Allow One-Off Photo-triggerable Gelation of Organo- and Hydrogelators.

[2]Rotaxanes displaying one-off photo-triggerable gelation properties have been synthesized through the "clipping" of photo-degradable macrocycles around the amide or urea functionalities of organo- and hydrogelators. Irradiation with UV-light cleaved the photo-labile macrocyclic components from the [2]rotaxanes, resulting in the free gelators being released into solution and, thereafter, forming gels. When the rate of gelation was sufficiently rapid, selective gelation of specific regions of the solution-and, indeed, photo-patterning of the solution-was possible.

[2]Catenanes Displaying Switchable Gin-Trap-Like Motion.

Sodium ion-controlled switching from "folded" to "linear" states results in significant changes in the molecular shape of a [2]catenane, such that it mimics the operation of a gin trap, with a fluorescent alarm signal appearing when pyrene side arms were present on its two macrocyclic components.

Na+ Ions Induce the Pirouetting Motion and Catalytic Activity of [2]Rotaxanes.

We have prepared [2]rotaxanes, the behavior of which as switchable catalysts depends on their pirouetting motion, which can be controlled through the addition and removal of Na+ ions. At least three sequential on/off cycles of a Michael reaction can be performed in situ when using the NaTFPB/[2.2.2]cryptand reagent pair to switch "on" and "off" the catalytic ability of the [2]rotaxanes.

Incarceration of Higher-Order Fullerenes within Cyclotriveratrylene-Based Hemicarcerands Allows Selective Isolation of C76 , C78 , and C84 from a Commercial Fullerene Mixture.

Size-complementary cyclotriveratrylene (CTV)-based hosts can incarcerate C76 , C78 , and C84 , thus allowing the selective isolation of these higher-order fullerenes from a commercially available mixture of fullerenes. The hemicarceplexes, formed after the encapsulation of the size-complementary fullerenes within the hosts, are isolated by column chromatography and released at elevated temperature, thereby leading to the isolation of C76 /C78 and C84 in good purities (up to 95 and 88 %, respectively).

Size effects in the alkali metal ion-templated formation of oligo(ethylene glycol)-containing [2]catenanes.

An investigation into the most suitable alkali metal ions for templating the assembly of [2]catenanes from di-, tri-, and tetra(ethylene glycol)-containing guest diamines and isophthalaldehyde has indicated that Na(+), K(+), and Rb(+) ions are optimal for preparing [2]catenanes containing at least one di(ethylene glycol) unit, two tri(ethylene glycol) units, and at least one tetra(ethylene glycol) unit [in the absence of a di(ethylene glycol) unit], respectively.

A redox-controllable molecular switch based on weak recognition of BPX26C6 at a diphenylurea station.

The Na+ ion-assisted recognition of urea derivatives by BPX26C6 has allowed the construction of a redox-controllable [2]rotaxane-type molecular switch based on two originally very weakly interacting host/guest systems. Using NOBF4 to oxidize the triarylamine terminus into a corresponding radical cation attracted the macrocyclic component toward its adjacent carbamate station; subsequent addition of Zn powder moved the macrocyclic component back to its urea station.

Cyclic [2]Catenane Dimers, Trimers, and Tetramers.

Dimeric, trimeric, and tetrameric cyclic [2]catenanes have been prepared directly through one-pot sodium-ion-templated dynamic imine formation from a diamine and a tetraaldehyde. NaBH4 mediated reduction of the labile imino bonds of these cyclic [2]catenane oligomers, followed by methylation of the resulting secondary amino groups enabled the isolation and characterization of oligomeric cyclic [2]catenanes as stable, covalently linked compounds.

Rotaxanes synthesized through sodium-ion-templated clipping of macrocycles around nonconjugated amide and urea functionalities.

A single urea or amide functionality in a dumbbell-shaped guest can be "clipped" by a macrocycle generated from a diamine and a dialdehyde through the templating effect of a Na(+) ion (see scheme). The resulting imine-containing rotaxanes can then be reduced to allow isolation of stable amine-based rotaxanes.

Hemicarceplexes modify the solubility and reduction potentials of C60.

A highly stable C60-incarcerated hemicarceplex, which retains its molecular integrity after heating at 523 K in air for at least 3 h, significantly increases the solubility of C60 in nonpolar solvents and increases the reduction potentials of the entrapped fullerene. Modification with [(η(5)-C5Me5)Ru(II)](+) dramatically increases the solubility of this hemicarceplex in polar, protic solvents (e.g., MeOH).

Five additional macrocycles that allow Na+ ion-templated threading of guest units featuring a single urea or amide functionality.

Five analogues of the macrocycle BPX26C6 are also capable of recognizing single urea and/or amide functionalities in the presence of templating Na(+) ions. We have unambiguously confirmed the formation of such [2]pseudorotaxane complexes in solution through syntheses of the corresponding [2]rotaxanes.

Using "threading followed by shrinking" to synthesize highly stable dialkylammonium-ion-based rotaxanes.

Herein, we report a "threading followed by shrinking" approach for the synthesis of rotaxanes by using an "oxygen-deficient" macrocycle that contained two arylmethyl sulfone units and the dumbbell-shaped salt bis(3,5-dimethylbenzyl)ammonium tetrakis(3,5-trifluoromethylphenyl)borate as the host and guest components, respectively. The extrusion of SO2 from both of the arylmethyl sulfone units of the macrocyclic component in the corresponding [2]pseudorotaxane resulted in a [2]rotaxane that was sufficiently stable to maintain its molecular integrity in CD3 SOCD3 at 393 K for at least 5 h.

Dual-Way-Switchable Ester Rotaxanes Constructed Using the Recognition of Malonate Diesters.

Malonate diesters can thread into the cavity of a di(ethylene glycol)-containing macrocycle under the templating effect of a Na+ ion; the corresponding rotaxanes can be synthesized with good efficiency by applying several stoppering reactions. A molecular switch, in which the interlocked macrocycle was moved between two rarely used stations (i.e., malonate and TAA) through the addition of acid/base and the presence/absence of Na+ ions, was constructed using this new recognition system.

Serotonin accumulation in transgenic rice by over-expressing tryptophan decarboxylase results in a dark brown phenotype and stunted growth.

A mutant M47286 with a stunted growth, low fertility and dark-brown phenotype was identified from a T-DNA-tagged rice mutant library. This mutant contained a copy of the T-DNA tag inserted at the location where the expression of two putative tryptophan decarboxylase genes, TDC-1 and TDC-3, were activated. Enzymatic assays of both recombinant proteins showed tryptophan decarboxylase activities that converted tryptophan to tryptamine, which could be converted to serotonin by a constitutively expressed tryptamine 5' hydroxylase (T5H) in rice plants. Over-expression of TDC-1 and TDC-3 in transgenic rice recapitulated the stunted growth, darkbrown phenotype and resulted in a low fertility similar to M47286. The degree of stunted growth and dark-brown color was proportional to the expression levels of TDC-1 and TDC-3. The levels of tryptamine and serotonin accumulation in these transgenic rice lines were also directly correlated with the expression levels of TDC-1 and TDC-3. A mass spectrometry assay demonstrated that the darkbrown leaves and hulls in the TDC-overexpressing transgenic rice were caused by the accumulation of serotonin dimer and that the stunted growth and low fertility were also caused by the accumulation of serotonin and serotonin dimer, but not tryptamine. These results represent the first evidence that over-expression of TDC results in stunted growth, low fertility and the accumulation of serotonin, which when converted to serotonin dimer, leads to a dark brown plant color.

A two-stage molecular retractable cable featuring push-button and rotary two-way switching modes.

A molecular cage based [2]rotaxane is reported in which the linear thread component can be elongated and contracted in a stepwise manner, mimicking a two-stage retractable cable that can be operated in both push-button (free-selection) and rotary (continuous-change) modes, depending on the choice of reagents.

Weakly associated TFPB anions are superior to PF6 anions when preparing (pseudo)rotaxanes from crown ethers and secondary dialkylammonium ions.

Making the right choice: Tetrakis(3,5-trifluoromethylphenyl)borate (TFPB) counter anions can facilitate the threading of dibenzylammonium (DBA(+)) ions through macrocycles in cases where the corresponding PF(6)(-) salts fail to exhibit complexation.