Exploring New Molecular Architectures for Anion Recognition: Synthesis and ATP Binding Properties of New Cyclam‐Based Ditopic Polyammonium Receptors.

Synthesis and characterization of three new polyamine receptors, composed of a cyclam unit (cyclam=1,4,8,11‐tetraazacyclotetradecane) linked by a 2,6‐dimethylpyridinyl spacer to the linear polyamines 1,4,8,11‐tetraazaundecane ( L1py ), 1,4,7‐triazaheptane ( L2py ), and to a quaternary ammonium group ( L3 py⁺ ), are reported. All receptors form highly charged polyammonium cations at neutral pH, suitable for anion recognition studies. ATP recognition was analyzed by using potentiometric, calorimetric, ¹H and ³¹P NMR measurements in aqueous solution. All receptors form 1:1 adducts with ATP in aqueous solution, stabilized by charge–charge and hydrogen‐bonding interactions between their ammonium groups and the anionic triphosphate chain of ATP. The binding ability of the three receptors for ATP increases in the order of L3 py⁺ < L2py < L1py . These adducts are stabilized by largely favourable entropic contributions, probably due to the large desolvation of the host and guest species upon complexation. The sequence observed for the binding affinity is explained in terms of the different ability of the three receptors to wrap around the phosphate chain of ATP.     

Bistable or Oscillating State Depending on Station and Temperature in Three‐Station Glycorotaxane Molecular Machines

High‐yield, straightforward synthesis of two‐ and three‐station [2]rotaxane molecular machines based on an anilinium, a triazolium, and a mono‐ or disubstituted pyridinium amide station is reported. In the case of the pH‐sensitive two‐station molecular machines, large‐amplitude movement of the macrocycle occurred. However, the presence of an intermediate third station led, after deprotonation of the anilinium station, and depending on the substitution of the pyridinium amide, either to exclusive localization of the macrocycle around the triazolium station or to oscillatory shuttling of the macrocycle between the triazolium and monosubstituted pyridinium amide station. Variable‐temperature ¹H NMR investigation of the oscillating system was performed in CD₂Cl₂. The exchange between the two stations proved to be fast on the NMR timescale for all considered temperatures (298–193 K). Interestingly, decreasing the temperature displaced the equilibrium between the two translational isomers until a unique location of the macrocycle around the monosubstituted pyridinium amide station was reached. Thermodynamic constants K were evaluated at each temperature: the thermodynamic parameters ΔH and ΔS were extracted from a Van′t Hoff plot, and provided the Gibbs energy ΔG. Arrhenius and Eyring plots afforded kinetic parameters, namely, energies of activation E_a, enthalpies of activation ΔH^≠, and entropies of activation ΔS^≠. The ΔG values deduced from kinetic parameters match very well with the ΔG values determined from thermodynamic parameters. In addition, whereas signal coalescence of pyridinium hydrogen atoms located next to the amide bond was observed at 205 K in the oscillating rotaxane and at 203 K in the two‐station rotaxane with a unique location of the macrocycle around the pyridinium amide, no separation of ¹H NMR signals of the considered hydrogen atoms was seen in the corresponding nonencapsulated thread. It is suggested that the macrocycle acts as a molecular brake for the rotation of the pyridinium–amide bond when it interacts by hydrogen bonding with both the amide NH and the pyridinium hydrogen atoms at the same time.     

Self‐Assembly of Calix[6]arene–Diazapyrenium Pseudorotaxanes: Interplay of Molecular Recognition and Ion‐Pairing Effects

The calix[6]arene wheel CX forms pseudorotaxane species with the diazapyrenium‐based axle 1? 2PF₆ in CH₂Cl₂ solution. The macrocyclic component is a heteroditopic receptor, which can complex the electron‐acceptor moiety of the axle inside its cavity and the counterions with the ureidic groups on the upper rim. The self‐assembled supramolecular species is a complex structure, which involves three components—the wheel, the axle and its counterions—that can mutually interact and affect. The stoichiometry of the resulting supramolecular complex depends on the nature and concentration of the counterions. Namely, it is observed that in dilute solution and with low‐coordinating anions the axle takes two wheels, whereas with highly coordinating anions or in concentrated solutions the complex has a 1:1 stoichiometry.     

All‐Optical Integrated Logic Operations Based on Chemical Communication between Molecular Switches

Molecular logic gates process physical or chemical “inputs” to generate “outputs” based on a set of logical operators. We report the design and operation of a chemical ensemble in solution that behaves as integrated AND, OR, and XNOR gates with optical input and output signals. The ensemble is composed of a reversible merocyanine‐type photoacid and a ruthenium polypyridine complex that functions as a pH‐controlled three‐state luminescent switch. The light‐triggered release of protons from the photoacid is used to control the state of the transition‐metal complex. Therefore, the two molecular switching devices communicate with one another through the exchange of ionic signals. By means of such a double (optical–chemical–optical) signal‐transduction mechanism, inputs of violet light modulate a luminescence output in the red/far‐red region of the visible spectrum. Nondestructive reading is guaranteed because the green light used for excitation in the photoluminescence experiments does not affect the state of the gate. The reset is thermally driven and, thus, does not involve the addition of chemicals and accumulation of byproducts. Owing to its reversibility and stability, this molecular device can afford many cycles of digital operation.     

Thioether‐Functionalized Quinone‐Based Resorcin[4]arene Cavitands: Electroswitchable Molecular Actuators

The utility of molecular actuators in nanoelectronics requires activation of mechanical motion by electric charge at the interface with conductive surfaces. We functionalized redox‐active resorcin[4]arene‐quinone cavitands with thioethers as surface‐anchoring groups at the lower rim and investigated their propensity to act as electroswitchable actuators that can adopt two different conformations in response to changes in applied potential. Molecular design was assessed by DFT calculations and X‐ray analysis. Electronic properties were experimentally studied in solution and thin films electrochemically, as well as by X‐ray photoelectron spectroscopy on gold substrates. The redox interconversion between the oxidized (quinone, Q ) and the reduced (semiquinone, SQ ) state was monitored by UV‐Vis‐NIR spectroelectrochemistry and EPR spectroscopy. Reduction to the SQ state induces a conformational change, providing the basis for potential voltage‐controlled molecular actuating devices.     

Synthesis of Planar Five‐Connected Nodal Ligands

The fiveway junction : The synthesis of ligands with five symmetrically diverging binding sites is described and their assembly into large spherical structures (such as that shown here) investigated.

     

Effects of Axle‐Core,Macrocycle, and Side‐Station Structures on the Threading and Hydrolysis Processes of Imine‐Bridged Rotaxanes

Imine‐bridged rotaxanes are a new type of rotaxane in which the axle and macrocyclic ring are connected by imine bonds. We have previously reported that in imine‐bridged rotaxane 5 , the shuttling motion of the macrocycle could be controlled by changing the temperature. In this study, we investigated how the axle and macrocycle structures affect the construction of the imine‐bridged rotaxane as well as the dynamic equilibrium between imine‐bridged rotaxane 5 and [2]rotaxane 7 by using various combinations of axles ( 1 A , B ), macrocycles ( 2 a – e ), and side‐stations (XYL and TEG). In the threading process, the flexibility of the macrocycle and the substituent groups at the para position of the aniline moieties affect the preparation of the threaded imines. The size of the imine‐bridging station and the macrocyclic tether affects the hydrolysis of the imine bonds under acidic conditions.     

A Cyclodextrin‐Based Photoresponsive Molecular Gate that Functions Independently of Either Solvent or Potentially Competitive Guests

The photoinduced interconversion between cinnamido‐substituted cyclodextrins constitutes a gating switch through which the substituent moves to open or block access to the cyclodextrin cavity. Most unusually for a cyclodextrin‐based device, the operation of this gate is solvent‐independent and unaffected by potentially competitive guests. It occurs in MeOH and DMSO, as well as in water. This contrasts with other cyclodextrin inclusion phenomena that are usually driven by hydrophobic effects and limited to aqueous media.     

Cucurbit[7]uril‐Dimethyllysine Recognition in a Model Protein

Here, we provide the first structural characterization of host–guest complexation between cucurbit[7]uril ( Q7 ) and dimethyllysine (KMe₂) in a model protein. Binding was dominated by complete encapsulation of the dimethylammonium functional group. While selectivity for the most sterically accessible dimethyllysine was observed both in solution and in the solid state, three different modes of Q7 ‐KMe₂ complexation were revealed by X‐ray crystallography. The crystal structures revealed also entrapped water molecules that solvated the ammonium group within the Q7 cavity. Remarkable Q7 ‐protein assemblies, including inter‐locked octahedral cages that comprise 24 protein trimers, occurred in the solid state. Cucurbituril clusters appear to be responsible for these assemblies, suggesting a strategy to generate controlled protein architectures.     

Directional Shuttling of a Stimuli‐Responsive Cone‐Like Macrocycle on a Single‐State Symmetric Dumbbell Axle

Rotaxane‐based molecular shuttles are often operated using low‐symmetry axles and changing the states of the binding stations. A molecular shuttle capable of directional shuttling of an acid‐responsive cone‐like macrocycle on a single‐state symmetric dumbbell axle is now presented. The axle contains three binding stations: one symmetric di(quaternary ammonium) station and two nonsymmetric phenyl triazole stations arranged in opposite orientations. Upon addition of an acid, the protonated macrocycle shuttles from the di(quaternary ammonium) station to the phenyl triazole binding station closer to its butyl groups. This directional shuttling presumably originates from charge repulsion and an orientational binding preference between the cone‐like cavity and the nonsymmetric phenyl triazole station. This mechanism for achieving directional shuttling by manipulating only the wheels instead of the tracks is new for artificial molecular machines.     

Structural Changes of a Doubly Spin‐Labeled Chemically Driven Molecular Shuttle Probed by PELDOR Spectroscopy

Gaining detailed information on the structural rearrangements associated with stimuli‐induced molecular movements is of utmost importance for understanding the operation of molecular machines. Pulsed electron–electron double resonance (PELDOR) was employed to monitor the geometrical changes arising upon chemical switching of a [2]rotaxane that behaves as an acid–base‐controlled molecular shuttle. To this aim, the rotaxane was endowed with stable nitroxide radical units in both the ring and axle components. The combination of PELDOR data and molecular dynamic calculations indicates that in the investigated rotaxane, the ring displacement along the axle, caused by the addition of a base, does not alter significantly the distance between the nitroxide labels, but it is accompanied by a profound change in the geometry adopted by the macrocycle.     

Single‐Walled Carbon Nanotube Based Molecular Switch Tunnel Junctions

This article describes two‐terminal molecular switch tunnel junctions (MSTJs) which incorporate a semiconducting, single‐walled carbon nanotube (SWNT) as the bottom electrode. The nanotube interacts noncovalently with a monolayer of bistable, nondegenerate [2]catenane tetracations, self‐organized by their supporting amphiphilic dimyristoylphosphatidyl anions which shield the mechanically switchable tetracations from a two‐micrometer wide metallic top electrode. The resulting 0.002 μm² area tunnel junction addresses a nanometer wide row of ≈2000 molecules. Active and remnant current–voltage measurements demonstrated that these devices can be reconfigurably switched and repeatedly cycled between high and low current states under ambient conditions. Control compounds, including a degenerate [2]catenane, were explored in support of the mechanical origin of the switching signature. These SWNT‐based MSTJs operate like previously reported silicon‐based MSTJs, but differently from similar devices incorporating bottom metal electrodes. The relevance of these results with respect to the choice of electrode materials for molecular electronics devices is discussed.     

Molecular Tweezers: Concepts and Applications

Taken to the molecular level, the concept of “tweezers” opens a rich and fascinating field at the convergence of molecular recognition, biomimetic chemistry and nanomachines. Composed of a spacer bridging two interaction sites, the behaviour of molecular tweezers is strongly influenced by the flexibility of their spacer. Operating through an “induced‐fit” recognition mechanism, flexible molecular tweezers select the conformation(s) most appropriate for substrate binding. Their adaptability allows them to be used in a variety of binding modes and they have found applications in chirality signalling. Rigid spacers, on the contrary, display a limited number of binding states, which lead to selective and strong substrate binding following a “lock and key” model. Exquisite selectivity may be expressed with substrates as varied as C₆₀, nanotubes and natural cofactors, and applications to molecular electronics and enzyme inhibition are emerging. At the crossroad between flexible and rigid spacers, stimulus‐responsive molecular tweezers controlled by ionic, redox or light triggers belong to the realm of molecular machines, and, applied to molecular tweezing, open doors to the selective binding, transport and release of their cargo. Applications to controlled drug delivery are already appearing. The past 30 years have seen the birth of molecular tweezers; the next many years to come will surely see them blooming in exciting applications.