Molecular-Pump-Enabled Synthesis of a Daisy Chain Polymer.

The assembly of a kinetically trapped daisy chain polymer under redox control has been achieved with a self-complementary monomer using an energy ratchet mechanism. The monomer is composed of a molecular pump at one end and a cyclobis(paraquat-p-phenylene) (CBPQT4+) ring at the other end. The pump and ring are linked together by a long collecting chain. When the monomer is reduced to its radical state, it self-assembles into a supramolecular daisy chain polymer on account of radical-pairing interactions. When all of the bipyridinium radical cations are quickly oxidized to dications, the CBPQT4+ rings are forced to thread onto the collecting chains, forming an out-of-equilibrium, kinetically trapped daisy chain polymer. This polymer can be switched reversibly back to the supramolecular polymer by reduction, followed by depolymerization to afford the monomer as a result of slow oxidation. This proof-of-concept investigation opens up opportunities for synthesizing mechanically interlocked polymers using molecular machines.

Stabilizing the Naphthalenediimide Radical within a Tetracationic Cyclophane.

Organic radicals are of importance in developing smart materials that have paramagnetic and/or near-infrared optical properties. Their practical applications, however, are limited by the labile nature of the radicals. Here, we demonstrate that by using a tetracationic cyclophane, namely, cyclobis(4,4'-(1,4-phenylene)bispyridine-p-phenylene) (ExBox4+), to encapsulate a naphthalenediimide (NDI) guest, the redox properties of NDI can be modulated. In organic solvents such as MeCN or DMF, ExBox4+ is able to provide the surrounding Coulombic attraction to the NDI•- radical anion and therefore enhance its stability toward oxidation. In water, NDI•- is prone to dimerization, forming its (NDI•-)2 dimer. Under UV-light irradiation, the (NDI•-)2 dimer is observed to disproportionate and yield the dianionic NDI2-. ExBox4+ is able to encapsulate the NDI•- radical anion and prevent its dimerization, and as a consequence, the radical anion is protected from further reduction in a noncovalent manner. We believe that our strategy of modulating the redox properties of NDI by either host-guest recognition or mechanical interlocking can aid and abet the development of radical-based materials, which could be employed in pursuit of applications in many areas, such as transporting spin and charges.

A Molecular Dual Pump.

Artificial molecular machines (AMMs) built from mechanically interlocked molecules (MIMs) can use energy ratchets to control the unidirectional motion of their component parts. These energy ratchets are operated by the alteration of kinetic barriers and thermodynamic wells, which are, in turn, determined by the switching on and off of noncovalent interactions. Previously, we have developed artificial molecular pumps (AMPs) capable of pumping rings consecutively onto a collecting chain as part of a molecular dumbbell, leading to the formation of rotaxanes. Here, we report a molecular dual pump (MDP) consisting of two individual AMPs linked in a head-to-tail fashion, wherein a single ring is pumped, in a linear manner, on and off a dumbbell involving a [2]rotaxane intermediate by exploiting the redox properties of the two pumps. This MDP, defined by the finely tuned noncovalent interactions and fueled by either chemicals or electricity, utilizes an energy ratchet mechanism to capture a ring and subsequently release it back into solution. The unidirectional motion and the resulting controlled capture and release of the ring were followed by 1D and 2D 1H NMR spectroscopy and supported by control experiments. This molecular dual pump may be considered to be a forerunner of AMMs that are capable of pumping rings across a membrane in a way similar to how bacteriorhodopsin transports protons from one side of a membrane to the other under the influence of light. Such extensive multicomponent AMMs can lead potentially to molecular transporting platforms with positional and directional control of cargo uptake and release when, and only when, instructed.

Epitaxial Growth of γ-Cyclodextrin-Containing Metal-Organic Frameworks Based on a Host-Guest Strategy.

A class of metal-organic frameworks (MOFs)-namely CD-MOFs-obtained from natural products has been grown in an epitaxial fashion as films on the surfaces of glass substrates, which are modified with self-assembled monolayers (SAMs) of γ-cyclodextrin (γ-CD) molecules. The SAMs are created by host-guest complexation of γ-CD molecules with surface-functionalized pyrene units. The CD-MOF films have continuous polycrystalline morphology with a structurally out-of-plane ( c-axial) orientation, covering an area of several square millimeters, with a thickness of ∼2 µm. Furthermore, this versatile host-guest strategy has been applied successfully in the growth of CD-MOFs as the shell on the curved surface of microparticles as well as in the integration of CD-MOF films into electrochemical devices for sensing carbon dioxide. In striking contrast to the control devices prepared from CD-MOF crystalline powders, these CD-MOF film-based devices display an enhancement in proton conductance of up to 300-fold. In addition, the CD-MOF film-based device exhibits more rapid and highly reversible CO2-sensing cycles under ambient conditions, with a 50-fold decrease in conductivity upon exposure to CO2 for 3 s which is recovered within 10 s upon re-exposure to air.

Mastering the non-equilibrium assembly and operation of molecular machines.

In mechanically interlocked compounds, such as rotaxanes and catenanes, the molecules are held together by mechanical rather than chemical bonds. These compounds can be engineered to have several well-defined mechanical states by incorporating recognition sites between the different components. The rates of the transitions between the recognition sites can be controlled by introducing steric "speed bumps" or electrostatically switchable gates. A mechanism for the absorption of energy can also be included by adding photoactive, catalytically active, or redox-active recognition sites, or even charges and dipoles. At equilibrium, these Mechanically Interlocked Molecules (MIMs) undergo thermally activated transitions continuously between their different mechanical states where every transition is as likely as its microscopic reverse. External energy, for example, light, external modulation of the chemical and/or physical environment or catalysis of an exergonic reaction, drives the system away from equilibrium. The absorption of energy from these processes can be used to favour some, and suppress other, transitions so that completion of a mechanical cycle in a direction in which work is done on the environment - the requisite of a molecular machine - is more likely than completion in a direction in which work is absorbed from the environment. In this Tutorial Review, we discuss the different design principles by which molecular machines can be engineered to use different sources of energy to carry out self-organization and the performance of work in their environments.

Influence of Constitution and Charge on Radical Pairing Interactions in Tris-radical Tricationic Complexes.

The results of a systematic investigation of trisradical tricationic complexes formed between cyclobis(paraquat-p-phenylene) bisradical dicationic (CBPQT(2(•+))) rings and a series of 18 dumbbells, containing centrally located 4,4'-bipyridinium radical cationic (BIPY(•+)) units within oligomethylene chains terminated for the most part by charged 3,5-dimethylpyridinium (PY(+)) and/or neutral 3,5-dimethylphenyl (PH) groups, are reported. The complexes were obtained by treating equimolar amounts of the CBPQT(4+) ring and the dumbbells containing BIPY(2+) units with zinc dust in acetonitrile solutions. Whereas UV-Vis-NIR spectra revealed absorption bands centered on ca. 1100 nm with quite different intensities for the 1:1 complexes depending on the constitutions and charges on the dumbbells, titration experiments showed that the association constants (Ka) for complex formation vary over a wide range, from 800 M(-1) for the weakest to 180 000 M(-1) for the strongest. While Coulombic repulsions emanating from PY(+) groups located at the ends of some of the dumbbells undoubtedly contribute to the destabilization of the trisradical tricationic complexes, solid-state superstructures support the contention that those dumbbells with neutral PH groups at the ends of flexible and appropriately constituted links to the BIPY(•+) units stand to gain some additional stabilization from C-H···π interactions between the CBPQT(2(•+)) rings and the PH termini on the dumbbells. The findings reported in this Article demonstrate how structural changes implemented remotely from the BIPY(•+) units influence their non-covalent bonding interactions with CBPQT(2(•+)) rings. Different secondary effects (Coulombic repulsions versus C-H···π interactions) are uncovered, and their contributions to both binding strengths associated with trisradical interactions and the kinetics of associations and dissociations are discussed at some length, supported by extensive DFT calculations at the M06-D3 level. A fundamental understanding of molecular recognition in radical complexes has relevance when it comes to the design and synthesis of non-equilibrium systems.

Wholly Synthetic Molecular Machines.

The past quarter of a century has witnessed an increasing engagement on the part of physicists and chemists in the design and synthesis of molecular machines de novo. This minireview traces the development of artificial molecular machines from their prototypes in the form of shuttles and switches to their emergence as motors and pumps where supplies of energy in the form of chemical fuel, electrochemical potential and light activation become a minimum requirement for them to function away from equilibrium. The challenge facing this rapidly growing community of scientists and engineers today is one of putting wholly synthetic molecules to work, both individually and as collections. Here, we highlight some of the recent conceptual and practical advances relating to the operation of wholly synthetic rotary and linear motors.

An Electrochromic Tristable Molecular Switch.

A tristable [2]catenane, composed of a macrocyclic polyether incorporating 1,5-dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units along with a 4,4'-bipyridinium (BIPY(•+)) radical cation as three very different potential recognition sites, interlocked mechanically with the tetracationic cyclophane, cyclobis(paraquat-p-phenylene) (CBPQT(4+)), was synthesized by donor-acceptor templation, employing a "threading-followed-by-cyclization" approach. In this catenane, movement of the CBPQT(4+) ring in its different redox states among these three potential recognition sites, with corresponding color changes, is achieved by tuning external redox potentials. In the starting state, where no external potential is applied, the ring encircles the TTF unit and displays a green color. Upon oxidation of the TTF unit, the CBPQT(4+) ring moves to the DNP unit, producing a red color. Finally, if all the BIPY(2+) units are reduced to BIPY(•+) radical cations, the resulting CBPQT(2(•+)) diradical dication will migrate to the BIPY(•+) unit, resulting in a purple color. These readily switchable electrochromic properties render the [2]catenane attractive for use in electro-optical devices.

Visible Light-Driven Artificial Molecular Switch Actuated by Radical-Radical and Donor-Acceptor Interactions.

We describe a visible light-driven switchable [2]catenane, composed of a Ru(bpy)3(2+) tethered cyclobis(paraquat-p-phenylene) (CBPQT(4+)) ring that is interlocked mechanically with a macrocyclic polyether consisting of electron-rich 1,5-dioxynaphthalene (DNP) and electron-deficient 4,4'-bipyridinium (BIPY(2+)) units. In the oxidized state, the CBPQT(4+) ring encircles the DNP recognition site as a consequence of favorable donor-acceptor interactions. In the presence of an excess of triethanolamine (TEOA), visible light irradiation reduces the BIPY(2+) units to BIPY((•+)) radical cations under the influence of the photosensitizer Ru(bpy)3(2+), resulting in the movement of the CBPQT(2(•+)) ring from the DNP to the BIPY((•+)) recognition site as a consequence of the formation of the more energetically favorable trisradical complex, BIPY((•+)) ⊂ CBPQT(2(•+)). Upon introducing O2 in the dark, the BIPY((•+)) radical cations are oxidized back to BIPY(2+) dications, leading to the reinstatement of the CBPQT(4+) ring encircled around the DNP recognition site. Employing this strategy of redox control, we have demonstrated a prototypical molecular switch that can be manipulated photochemically and chemically by sequential reduction and oxidation.

Redox switchable daisy chain rotaxanes driven by radical-radical interactions.

We report the one-pot synthesis and electrochemical switching mechanism of a family of electrochemically bistable 'daisy chain' rotaxane switches based on a derivative of the so-called 'blue box' (BB(4+)) tetracationic cyclophane cyclobis(paraquat-p-phenylene). These mechanically interlocked molecules are prepared by stoppering kinetically the solution-state assemblies of a self-complementary monomer comprising a BB(4+) ring appended with viologen (V(2+)) and 1,5-dioxynaphthalene (DNP) recognition units using click chemistry. Six daisy chains are isolated from a single reaction: two monomers (which are not formally 'chains'), two dimers, and two trimers, each pair of which contains a cyclic and an acyclic isomer. The products have been characterized in detail by high-field (1)H NMR spectroscopy in CD3CN-made possible in large part by the high symmetry of the novel BB(4+) functionality-and the energies associated with certain aspects of their dynamics in solution are quantified. Cyclic voltammetry and spectroelectrochemistry have been used to elucidate the electrochemical switching mechanism of the major cyclic daisy chain products, which relies on spin-pairing interactions between V(•+) and BB(2(•+)) radical cations under reductive conditions. These daisy chains are of particular interest as electrochemically addressable molecular switches because, in contrast with more conventional bistable catenanes and rotaxanes, the mechanical movement of the ring between recognition units is accompanied by significant changes in molecular dimensions. Whereas the self-complexed cyclic monomer-known as a [c1]daisy chain or molecular 'ouroboros'-conveys sphincter-like constriction and dilation of its ultramacrocyclic cavity, the cyclic dimer ([c2]daisy chain) expresses muscle-like contraction and expansion along its molecular length.

Energetically demanding transport in a supramolecular assembly.

A challenge in contemporary chemistry is the realization of artificial molecular machines that can perform work in solution on their environments. Here, we report on the design and production of a supramolecular flashing energy ratchet capable of processing chemical fuel generated by redox changes to drive a ring in one direction relative to a dumbbell toward an energetically uphill state. The kinetics of the reaction pathway juxtapose a low energy [2]pseudorotaxane that forms under equilibrium conditions with a high energy, metastable [2]pseudorotaxane which resides away from equilibrium.

Pillar[5]arene as a co-factor in templating rotaxane formation.

After the manner in which coenzymes often participate in the binding of substrates in the active sites of enzymes, pillar[5]arene, a macrocycle containing five hydroquinone rings linked through their para positions by methylene bridges, modifies the binding properties of cucurbit[6]uril, such that the latter templates azide-alkyne cycloadditions that do not occur in the presence of only the cucurbit[6]uril, a macrocycle composed of six glycoluril residues doubly linked through their nitrogen atoms to each other by methylene groups. Here, we describe how a combination of pillar[5]arene and cucurbit[6]uril interacts cooperatively with bipyridinium dications substituted on their nitrogen atoms with 2-azidoethyl- to 5-azidopentyl moieties to afford, as a result of orthogonal templation, two [4]rotaxanes and one [5]rotaxane in >90% yields inside 2 h at 55 °C in acetonitrile. Since the hydroxyl groups on pillar[5]arene and the carbonyl groups on cucurbit[6]uril form hydrogen bonds readily, these two macrocycles work together in a cooperative fashion to the extent that the four conformational isomers of pillar[5]arene can be trapped on the dumbbell components of the [4]rotaxanes. In the case of the [5]rotaxane, it is possible to isolate a compound containing two pillar[5]arene rings with local C5 symmetries. In addition to fixing the stereochemistries of the pillar[5]arene rings, the regiochemistries associated with the 1,3-dipolar cycloadditions have been extended in their constitutional scope. Under mild conditions, orthogonal recognition motifs have been shown to lead to templation with positive cooperativity that is fast and all but quantitative, as well as being green and efficient.

Relative unidirectional translation in an artificial molecular assembly fueled by light.

Motor molecules present in nature convert energy inputs, such as a chemical fuel or incident photons of light, into directed motion and force biochemical systems away from thermal equilibrium. The ability not only to control relative movements of components in molecules but also to drive their components preferentially in one direction relative to each other using versatile stimuli is one of the keys to future technological applications. Herein, we describe a wholly synthetic small-molecule system that, under the influence of chemical reagents, electrical potential, or visible light, undergoes unidirectional relative translational motion. Altering the redox state of a cyclobis(paraquat-p-phenylene) ring simultaneously (i) inverts the relative heights of kinetic barriers presented by the two termini--one a neutral 2-isopropylphenyl group and the other a positively charged 3,5-dimethylpyridinium unit--of a constitutionally asymmetric dumbbell, which can impair the threading/dethreading of a [2]pseudorotaxane, and (ii) controls the ring's affinity for a 1,5-dioxynaphthalene binding site located in the dumbbell's central core. The formation and subsequent dissociation of the [2]pseudorotaxane by passage of the ring over the neutral and positively charged termini of the dumbbell component in one, and only one, direction relatively defined has been demonstrated by (i) spectroscopic ((1)H NMR and UV/vis) means and cyclic voltammetry as well as with (ii) DFT calculations and by (iii) comparison with control compounds in the shape of constitutionally symmetrical [2]pseudorotaxanes, one with two positively charged ends and the other with two neutral ends. The operation of the system relies solely on reversible, yet stable, noncovalent bonding interactions. Moreover, in the presence of a photosensitizer, visible-light energy is the only fuel source that is needed to drive the unidirectional molecular translation, making it feasible to repeat the operation numerous times without the buildup of byproducts.

Asararenes--a family of large aromatic macrocycles.

We announce the establishment of a new family of macrocycles--the asararenes, which are based on para-methylene linked "asarol methyl ether" (1,2,4,5-tetramethoxybenzene) units. Macrocycles with 6-12 aromatic units have been synthesized and isolated in a single step from asarol methyl ether and paraformaldehyde. Even larger rings, with up to 15 asarol methyl ether units, have been observed by high-resolution mass spectrometry. Single-crystal X-ray structures of asar[6]-, asar[7]-, asar[8]-, asar[9]-, asar[10]- and asar[11]arene highlight the diverse structural features of this family of macrocycles. While the cavities of the asar[6-8]arene macrocycles are mostly filled with methoxyl groups, the asar[9]- and asar[10]arene rings contain accessible cavities and self-assemble into infinite channels filled with solvent molecules in the solid state. These solid-state structures highlight the potential of this family of macrocycles for a wide range of potential applications.

Electron sharing and anion-π recognition in molecular triangular prisms.

Stacking on a full belly: Triangular molecular prisms display electron sharing among their triangularly arranged naphthalenediimide (NDI) redox centers. Their electron-deficient cavities encapsulate linear triiodide anions, leading to the formation of supramolecular helices in the solid state. Chirality transfer is observed from the six chiral centers of the filled prisms to the single-handed helices.

Dynamic combinatorial libraries of a dimercapto-pillar[5]arene.

We report the synthesis and dynamic covalent chemistry (DCvC) of an A1/A2-dimercapto-functionalized pillar[5]arene (Di-SH-P5). The introduction of thiol moieties into this macrocyclic host makes it an effective building block for making a dynamic combinatorial library (DCL), giving rise to a set of cyclic trimers with intriguing host-guest properties as the dominant constituents.

Mono-mercapto-functionalized pillar[5]arene: a host-guest complexation accelerated reversible redox dimerization.

A mono-mercapto-functionalized pillar[5]arene and its dimer, capable of being reversibly interconverted, were successfully synthesized. Fascinatingly, a faster reversible redox conversion involving a dynamic disulfide bond was observed between their host-guest complexes compared with the hosts themselves.

A precise polyrotaxane synthesizer.

Mechanically interlocked molecules are likely candidates for the design and synthesis of artificial molecular machines. Although polyrotaxanes have already found niche applications in exotic materials with specialized mechanical properties, efficient synthetic protocols to produce them with precise numbers of rings encircling their polymer dumbbells are still lacking. We report the assembly line-like emergence of poly[n]rotaxanes with increasingly higher energies by harnessing artificial molecular pumps to deliver rings in pairs by cyclical redox-driven processes. This programmable strategy leads to the precise incorporation of two, four, six, eight, and 10 rings carrying 8+, 16+, 24+, 32+, and 40+ charges, respectively, onto hexacationic polymer dumbbells. This strategy depends precisely on the number of redox cycles applied chemically or electrochemically, in both stepwise and one-pot manners.

Guest recognition enhanced by lateral interactions.

A hexacationic triangular covalent organic cage, AzaEx2Cage 6+, has been synthesized by means of a tetrabutylammonium iodide-catalyzed SN2 reaction. The prismatic cage is composed of two triangular 2,4,6-triphenyl-1,3,5-triazine (TPT) platforms bridged face-to-face by three 4,4'-bipyridinium (BIPY 2+) spacers. The rigidity of these building blocks leads to a shape-persistent cage cavity with an inter-platform distance of approximately 11.0 Å. This distance allows the cage to accommodate two aromatic guests, each of which is able to undergo π-π interactions with one of the two TPT platform simultaneously, in an A-D-D-A manner. In the previously reported prism-shaped cage, the spacers (pillars) are often considered passive or non-interactive. In the current system, the three BIPY 2+ spacers are observed to play an important role in guest recognition. Firstly, the BIPY 2+ spacers are able to interact with the carbonyl group in a pyrene-1-carbaldehyde (PCA) guest, by introducing lateral dipole-cation or dipole-dipole interactions. As a consequence, the binding affinity of the cage towards the PCA guest is significantly larger than that of pyrene as the guest, even although the latter is often considered to be a better π-electron donor. Secondly, in the case of the guest 1,5-bis[2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)ethoxy]naphthalene (BH4EN), the pillars can provide higher binding forces compared to the TPT platform. Hence, peripheral complexation occurs when AzaEx2Cage 6+ accommodates BH4EN in MeCN. Thirdly, when both PCA and BH4EN are added into a solution of AzaEx2Cage 6+, inclusion and peripheral complexation occur simultaneously to PCA and BH4EN respectively, even though the accommodation of the former guest seems to attenuate the external binding of the latter. This discovery of the importance of lateral interactions highlights the relationship between the electrostatic properties of a highly charged host and its complexation behavior, and as such, provides insight into the design of more complex hosts that bind guests in multiple locations and modes.

Molecular Russian dolls.

The host-guest recognition between two macrocycles to form hierarchical non-intertwined ring-in-ring assemblies remains an interesting and challenging target in noncovalent synthesis. Herein, we report the design and characterization of a box-in-box assembly on the basis of host-guest radical-pairing interactions between two rigid diradical dicationic cyclophanes. One striking feature of the box-in-box complex is its ability to host various 1,4-disubstituted benzene derivatives inside as a third component in the cavity of the smaller of the two diradical dicationic cyclophanes to produce hierarchical Russian doll like assemblies. These results highlight the utility of matching the dimensions of two different cyclophanes as an efficient approach for developing new hybrid supramolecular assemblies with radical-paired ring-in-ring complexes and smaller neutral guest molecules.