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.

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.

Metal-Ion-Induced Mechanical Chirality: Achiral Rotaxane as the Only Ligand in Chiral Palladium(II)-N-Heterocyclic Carbene Complexes.

We report the insertion of Pd(II) into an originally achiral rotaxane producing two chiral metallorotaxanes: one is planar-chiral, with its two interlocked components both chelating nonequivalently to the metal center; the other is C2-symmetrical-chiral, with the dynamically exchangeable stereogenic units stabilized by the interlocked structure. Chiral additives confirmed the existence of chirality, with the enantiomers of the C2-symmetrical N-heterocyclic carbene complex being resolved using chiral TRISPHAT counteranions.

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.

Using Slippage to Construct a Prototypical Molecular "Lock & Lock" Box.

We report a new slippage system based on p-tert-butylbenzyl-terminated imidazolium ions and di(ethylene glycol)-containing macrocycles and their use as linking units for the construction of a prototypical molecular "Lock & Lock" box from a resorcinarene-based cavitand "bowl" and a porphyrin "cover". The multivalent structure with four slippage linkers provided the molecular box with high stability, yet the system dissociated into its two components upon application of suitable external stimuli.

Interlocking increases the persistence of N-heterocyclic carbenes in solution.

In this study imidazolium and imidazolinium centers in precursor [2]rotaxanes were deprotonated to obtain interlocked molecules featuring stabilized N-heterocyclic carbene centers. The encircling macrocyclic components enhanced the persistence of the otherwise unstable imidazolidin-2-ylidenes in solution at 253 K for more than a week in the absence of air.

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.

Absolute Configurations of Topologically Chiral [2]Catenanes and the Acid/Base-Flippable Directions of Their Optical Rotations.

The absolute configurations of the two enantiomers of a topologically chiral [2]catenane were determined unambiguously based on HPLC resolution and X-ray crystal analysis. Although structurally dissimilar to simple amino acids, the optical rotations of these separated [2]catenanes share the Clough-Lutz-Jirgensons behavior of amino acids: the optical rotation flips direction in the presence of acid and base, the first example of such behavior for a mechanically interlocked topologically chiral catenane.

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.

[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.

Synthesis of Oxygen-Free [2]Rotaxanes: Recognition of Diarylguanidinium Ions by Tetraazacyclophanes.

Simple cyclophanes containing four distant amino N atoms or ether O atoms behave as hosts for the threading of guest diarylguanidinium ions. The recognition system exhibits high synthetic flexibility, allowing unique O-free [2]rotaxanes to be synthesized efficiently (yields of up to 80%) through both "threading-followed-by-stoppering" and "clipping" approaches.

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.

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.

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.

Synthesizing [2]Rotaxanes and [2]Catenanes through Na(+)-Templated Clipping of Macrocycles around Oligo(ethylene glycol) Units.

Di-, tri-, and tetra(ethylene glycol) units in both dumbbell-shaped and macrocyclic molecules can be used as primary recognition units for the clipping of macrocycles in the presence of templating Na(+) ions to form corresponding [2]rotaxanes and [2]catenanes. One such tri(ethylene glycol)-containing [2]catenane behaves as a Na(+) ion-controllable molecular switch.

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.

Hemicarceplex formation allows ready identification of the isomers of the metallofullerene Sc3N@C80 using (1)H and (13)C NMR spectroscopy.

A cyclotriveratrylene-based molecular cage forms hemicarceplexes that significantly increase the solubility of commercially available Sc3N@C80 in CDCl3. When incarcerated within the molecular cage, the two structural isomers of this metallofullerene, Sc3N@D5h-C80 and Sc3N@Ih-C80, displayed characteristic signals in both (1)H and (13)C NMR spectra, allowing direct identification of each isomer without the need to enrich the sample with (13)C atoms.