An electric molecular motor.

Macroscopic electric motors continue to have a large impact on almost every aspect of modern society. Consequently, the effort towards developing molecular motors1-3 that can be driven by electricity could not be more timely. Here we describe an electric molecular motor based on a [3]catenane4,5, in which two cyclobis(paraquat-p-phenylene)6 (CBPQT4+) rings are powered by electricity in solution to circumrotate unidirectionally around a 50-membered loop. The constitution of the loop ensures that both rings undergo highly (85%) unidirectional movement under the guidance of a flashing energy ratchet7,8, whereas the interactions between the two rings give rise to a two-dimensional potential energy surface (PES) similar to that shown by FOF1 ATP synthase9. The unidirectionality is powered by an oscillating10 voltage11,12 or external modulation of the redox potential13. Initially, we focused our attention on the homologous [2]catenane, only to find that the kinetic asymmetry was insufficient to support unidirectional movement of the sole ring. Accordingly, we incorporated a second CBPQT4+ ring to provide further symmetry breaking by interactions between the two mobile rings. This demonstration of electrically driven continual circumrotatory motion of two rings around a loop in a [3]catenane is free from the production of waste products and represents an important step towards surface-bound14 electric molecular motors.

Discrete Open-Shell Tris(bipyridinium radical cationic) Inclusion Complexes in the Solid State.

The solid-state properties of organic radicals depend on radical-radical interactions that are influenced by the superstructure of the crystalline phase. Here, we report the synthesis and characterization of a substituted tetracationic cyclophane, cyclobis(paraquat-p-1,4-dimethoxyphenylene), which associates in its bisradical dicationic redox state with the methyl viologen radical cation (MV•+) to give a 1:1 inclusion complex. The (super)structures of the reduced cyclophane and this 1:1 complex in the solid state deviate from the analogous (super)structures observed for the reduced state of cyclobis(paraquat-p-phenylene) and that of its trisradical tricationic complex. Titration experiments reveal that the methoxy substituents on the p-phenylene linkers do not influence binding of the cyclophane toward small neutral guests-such as dimethoxybenzene and tetrathiafulvalene-whereas binding of larger radical cationic guests such as MV•+ by the reduced cyclophane decreases 10-fold. X-ray diffraction analysis reveals that the solid-state superstructure of the 1:1 complex constitutes a discrete entity with weak intermolecular orbital overlap between neighboring complexes. Transient nutation EPR experiments and DFT calculations confirm that the complex has a doublet spin configuration in the ground state as a result of the strong orbital overlap, while the quartet-state spin configuration is higher in energy and inaccessible at ambient temperature. Superconducting quantum interference device (SQUID) measurements reveal that the trisradical tricationic complexes interact antiferromagnetically and form a one-dimensional Heisenberg antiferromagnetic chain along the a-axis of the crystal. These results offer insights into the design and synthesis of organic magnetic materials based on host-guest complexes.

Light-Switchable Buffers.

A visible light-switchable buffer system based on a merocyanine photoacid is presented. Para-substitution of the indolium side with a methoxy group affords a compound suitable for making hydrolytically stable aqueous buffers whose pH can be tuned between 7 and 4 using 500 nm light.

A Dynamic Tetracationic Macrocycle Exhibiting Photoswitchable Molecular Encapsulation.

Designing macrocycles with appropriate molecular recognition features that allow for the integration of suitable external stimuli to control host-guest processes is a challenging endeavor which enables molecular containers to solubilize, stabilize, and separate chemical entities in an externally controllable manner. Herein, we introduce photo- and thermal-responsive elements into a semi-rigid tetracationic cyclophane, OPVEx2Box4+, that is composed of oligo( p-phenylenevinylene) pyridinium units and the biphenylene-bridged 4,4-bipyridinium extended viologens and adopts a rectangle-like geometry. It transpires that when the photoactive oligo( p-phenylenevinylene) pyridinium unit is incorporated in a macrocyclic scaffold, its reversibility is dramatically improved, and the configurations of the cyclophane can go back and forth between ( EE)- and ( EZ)-isomers upon alternating blue light irradiation and heating. When the macrocycle is found in its ( EE)-configuration, it is capable of binding various π-electron-rich guests-e.g., anthracene and perylene-as well as π-electron-deficient guests-e.g., 9,10-anthraquinone and 5,12-tetracenequinone-through charge-transfer and van der Waals interactions. When irradiated with blue light, the ( EE)-isomer of the cyclophane can be transformed successfully to the ( EZ)-isomer, resulting in the switching off of the binding affinity for guest molecules, which are bound once again upon heating. The use of light and heat as external stimuli to control host-guest interactions involving a multi-responsive host and various guests provides us with a new opportunity to design and construct more-advanced molecular switches and machines.

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.

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.

Controlling Dual Molecular Pumps Electrochemically.

Artificial molecular machines can be operated using either physical or chemical inputs. Light-powered motors display clean and autonomous operations, whereas chemically driven machines generate waste products and are intermittent in their motions. Herein, we show that controlled changes in applied electrochemical potentials can drive the operation of artificial molecular pumps in a semi-autonomous manner-that is, without the need for consecutive additions of chemical fuel(s). The electroanalytical approach described in this Communication promotes the assembly of cyclobis(paraquat-p-phenylene) rings along a positively charged oligomeric chain, providing easy access to the formation of multiple mechanical bonds by means of a controlled supply of electricity.

Photoswitchable Catalysis by a Nanozyme Mediated by a Light-Sensitive Cofactor.

The activity of a gold nanoparticle-based catalyst can be reversibly up- and down-regulated by light. Light is used to switch a small molecule between cis- and trans-isomers, which inhibits the catalytic activity of the nanoparticles to different extent. The system is functional in aqueous buffer, which paves the way for integrating the system in biological networks.

Redox-Active Macrocycles for Organic Rechargeable Batteries.

Organic rechargeable batteries, composed of redox-active molecules, are emerging as candidates for the next generation of energy storage materials because of their large specific capacities, cost effectiveness, and the abundance of organic precursors, when compared with conventional lithium-ion batteries. Although redox-active molecules often display multiple redox states, precise control of a molecule's redox potential, leading to a single output voltage in a battery, remains a fundamental challenge in this popular field of research. By combining macrocyclic chemistry with density functional theory calculations (DFT), we have identified a structural motif that more effectively delocalizes electrons during lithiation events in battery operations-namely, through-space electron delocalization in triangular macrocyclic molecules that exhibit a single well-defined voltage profile-compared to the discrete multiple voltage plateaus observed for a homologous macrocyclic dimer and an acyclic derivative of pyromellitic diimide (PMDI). The triangular macrocycle, incorporating three PMDI units in close proximity to one another, exhibits a single output voltage at 2.33 V, compared with two peaks at (i) 2.2 and 1.95-1.60 V for reduction and (ii) 1.60-1.95 and 2.37 V for oxidation of the acyclic PMDI derivative. By investigating the two cyclic derivatives with different conformational dispositions of their PMDI units and the acyclic PMDI derivative, we identified noticeable changes in interactions between the PMDI units in the two cyclic derivatives under reducing conditions, as determined by differential pulse voltammetry, solution-state spectroelectrochemistry, and variable-temperature UV-Vis spectra. The numbers and relative geometries of the PMDI units are found to alter the voltage profile of the active materials significantly during galvanostatic measurements, resulting in a desirable single plateau for the triangular macrocycle. The present investigation reveals that understanding and controlling the relative conformational dispositions of redox-active units in macrocycles are key to achieving high energy density and long cycle-life electrodes for organic rechargeable batteries.

Chiral Nanozymes-Gold Nanoparticle-Based Transphosphorylation Catalysts Capable of Enantiomeric Discrimination.

Enantioselectivity in RNA cleavage by a synthetic metalloenzyme has been demonstrated for the first time. Thiols containing chiral Zn(II) -binding head groups have been self-assembled on the surface of gold nanoparticles. This results in the spontaneous formation of chiral bimetallic catalytic sites that display different activities (kcat ) towards the enantiomers of an RNA model substrate. Substrate selectivity is observed when the nanozyme is applied to the cleavage of the dinucleotides UpU, GpG, ApA, and CpC, and remarkable differences in reactivity are observed for the cleavage of the enantiomerically pure dinucleotide UpU.

Catalytic signal amplification for the discrimination of ATP and ADP using functionalised gold nanoparticles.

Diagnostic assays that incorporate a signal amplification mechanism permit the detection of analytes with enhanced selectivity. Herein, we report a gold nanoparticle-based chemical system able to differentiate ATP from ADP by means of catalytic signal amplification. The discrimination between ATP and ADP is of relevance for the development of universal assays for the detection of enzymes which consume ATP. For example, protein kinases are a class of enzymes critical for the regulation of cellular functions, and act to modulate the activity of other proteins by transphosphorylation, transferring a phosphate group from ATP to give ADP as a byproduct. The system described here exploits the ability of cooperative catalytic head groups on gold nanoparticles to very efficiently catalyze chromogenic reactions such as the transphosphorylation of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNPP). A series of chromogenic substrates have been synthesized and evaluated by means of Michaelis-Menten kinetics (compounds 2, 4-6). 2-Hydroxypropyl-(3-trifluoromethyl-4-nitro)phenyl phosphate (5) was found to display higher reactivity (kcat) and higher binding affinity (KM) when compared to HPNPP. This higher binding affinity allows phosphate 5 to compete with ATP and ADP to different extents for binding on the monolayer surface, thus enabling a catalytically amplified signal only when ATP is absent. Overall, this represents a viable new approach for monitoring the conversion of ATP into ADP with high sensitivity.

Label-free fluorescence detection of kinase activity using a gold nanoparticle based indicator displacement assay.

A straightforward indicator-displacement assay (IDA) has been developed for the quantitative analysis of ATP→ADP conversion. The IDA relies on the use of gold nanoparticles passivated with a monolayer of thiols terminating with a 1,4,7-triazacyclononane (TACN)·Zn(2+) head group. The analytes ATP and ADP compete to a different extent with a fluorescent probe for binding to the monolayer surface. In the presence of ATP the fluorescent probe is free in solution, whereas in the presence of ADP the fluorescent probe is captured by the nanoparticles and its fluorescence is quenched. The linear response of the fluorescence signal towards different ratios of ATP : ADP permitted the detection of protein kinase activity simply by adding aliquots of the enzyme solution to the assay solution followed by measurement of the fluorescent intensity. The assay poses no restrictions on the target kinase nor does it require labeling of the kinase substrate. The assay was tested on the protein kinases PIM-1 and Src and validated through a direct comparison with the classical radiometric assay using the [γ-(32)P]-labeled ATP.

Multivalent interactions regulate signal transduction in a self-assembled Hg2+ sensor.

A self-assembled sensing system able to detect Hg(2+) at low nanomolar concentrations is reported that operates through a signal transduction pathway involving multivalent interactions. The analyte causes dimerization of low-affinity ligands, resulting in a complex with a high affinity for a multivalent monolayer-protected gold nanoparticle (AuNP). This complex displaces a quenched fluorescent reporter from the AuNP, resulting in a turn ON of fluorescence. It is shown that the strength of the output signal can be regulated by tuning the multivalent interactions between the complex and the NP. Finally, it is shown that multivalent interactions drive the self-selection of a high-affinity complex from a mixture of low-affinity ligands.

Zn2+-regulated self-sorting and mixing of phosphates and carboxylates on the surface of functionalized gold nanoparticles.

Herein, we describe the self-sorting of phosphate- and carboxylate-containing molecules on the surface of monolayer-protected gold nanoparticles. Self-sorting is driven by selective interactions between the phosphate probe and Zn(2+) complexes in one monolayer; these interactions force the carboxylate probe to move to a second type of nanoparticle. This process effectively separates the probes and causes their localization in well-defined spaces surrounding the nanoparticles. The removal/addition of Zn(2+) metal ions from the system is used to convert the system from an ordered to a disordered state and vice versa. The possibility to control the location and transport of populations of molecules in a complex mixture creates new perspectives for the development of innovative complex catalytic systems that mimic nature.

Controlling supramolecular complex formation on the surface of a monolayer-protected gold nanoparticle in water.

A combination of hydrophobic and electrostatic interactions drives the self-assembly of a large number of small molecules on the surface of a monolayer-protected gold nanoparticle. The hydrophobic interactions originate from the insertion of an aromatic unit in the hydrophobic part of the monolayer. This is evidenced by a shift in the emission wavelength of the fluorogenic probe upon binding. Up to around 35 small molecules can be simultaneously bound to the monolayer surface at micromolar concentrations in water. It is shown that an understanding of the supramolecular interactions that drive complex formation on the monolayer surface provides unprecedented control over the supramolecular chemistry occurring on the surface. By taking advantage of the different kinds of noncovalent interactions present in different probes, it is possibile to displace one type of surface-bound molecule from a heteromeric surface selectively. Finally, it is also possible to catch and release one type of surface-bound molecule selectively.

Controlling DNA nanodevices with light-switchable buffers.

Control over synthetic DNA-based nanodevices can be achieved with a variety of physical and chemical stimuli. Actuation with light, however, is as advantageous as difficult to implement without modifying DNA strands with photo-switchable groups. Herein, we show that DNA nanodevices can be controlled using visible light in photo-switchable aqueous buffer solutions in a reversible and highly programmable fashion. The strategy presented here is non-invasive and allows the remote control with visible light of complex operations of DNA-based nanodevices such as the reversible release/loading of cargo molecules.

Reversible control over the valency of a nanoparticle-based supramolecular system.

The reversible "catch-and-release" of small molecules from the surface of monolayer-protected gold nanoparticles is described. The valency of the system (i.e., the number of molecules bound to the surface) can be controlled through the addition and removal of metal ions from the monolayer. Both the change in valency and the release rate of the molecules are strongly pH-dependent. The release rate can be regulated by altering the ratio of metal ions in the monolayer.

Light-induced assembly and disassembly of polymers with Pd n L2n -type network junctions.

Polymers containing Pd n L2n complexes as network junctions were obtained by reaction of poly(ethylene glycol)-linked N-donor ligands with Pd2+. The addition of a metastable state photoacid renders the networks light sensitive, and gel-sol transitions can be achieved by irradiation with light. The inverse process, a light-induced sol-gel transition, was realized by using a molecularly defined Pd complex as an acid-sensitive reservoir for Pd2+. Upon irradiation, Pd2+ ions are released, allowing the formation of an acid-resistant polymer network. Both the gel-sol and the sol-gel transitions are reversed in the dark.

Correction: Light-induced assembly and disassembly of polymers with Pd n L2n -type network junctions.

[This corrects the article DOI: 10.1039/D1SC00127B.].

SET processes in Lewis acid-base reactions: the tritylation of N-heterocyclic carbenes.

Reactions between N-heterocyclic carbenes (NHCs) and the trityl cation, [Ph3C]+, give covalent adducts of type [NHC-CPh3]+ and/or [NHC-C6H5-CPh2]+. EPR spectroscopy, UV-Vis analyses, and trapping experiments imply that adduct formation involves carbene radical cations and the trityl radical. The results demonstrate that single electron transfer (SET) processes should be considered for reaction of NHCs with oxidizing Lewis acids.