Euan R. Kay

A molecular information ratchet

Motor proteins and other biological machines are highly efficient at converting energy into directed motion and driving chemical systems away from thermodynamic equilibrium. But even though these biological structures have inspired the design of many molecules that mimic aspects of their behaviour, artificial nanomachine systems operate almost exclusively by moving towards thermodynamic equilibrium, not away from it. Here we show that information about the location of a macrocycle in a rotaxane—a molecular ring threaded onto a molecular axle—can be used, on the input of light energy, to alter the kinetics of the shuttling of the macrocycle between two compartments on the axle. For an ensemble of such molecular machines, the macrocycle distribution is directionally driven away from its equilibrium value without ever changing the relative binding affinities of the ring for the different parts of the axle. The selective transport of particles between two compartments by brownian motion in this way bears similarities to the hypothetical task performed without an energy input by a ‘demon’ in Maxwell’s famous thought experiment. Our observations demonstrate that synthetic molecular machines can operate by an information ratchet mechanism, in which knowledge of a particle’s position is used to control its transport away from equilibrium.

Rise of the Molecular Machines

The authors thank the EPSRC, ERC, and the Leverhulme Trust for supporting our research programs on molecular machines. E.R.K. is a Royal Society of Edinburgh/Scottish Government Personal Research Fellow.

Three State Redox-Active Molecular Shuttle That Switches in Solution and on a Surface

Although the desirability of developing synthetic molecular machine systems that can function on surfaces is widely recognized, to date the only well-characterized examples of electrochemically switchable rotaxane-based molecular shuttles which can do so are based on the tetracationic viologen macrocycle pioneered by Stoddart. Here, we report on a [2]rotaxane which features succinamide and naphthalene diimide hydrogen-bonding stations for a benzylic amide macrocycle that can shuttle and switch its net position both in solution and in a monolayer. Three oxidation states of the naphthalene diimide unit can be accessed electrochemically in solution, each one with a different binding affinity for the macrocycle and, hence, corresponding to a different distribution of the rings between the two stations in the molecular shuttle. Cyclic voltammetry experiments show the switching to be both reversible and cyclable and allow quantification of the translational isomer ratios (thermodynamics) and shuttling dynamics (kinetics) for their interconversion in each state. Overall, the binding affinity of the naphthalene diimide station can be changed by 6 orders of magnitude over the three states. Unlike previous electrochemically active amide-based molecular shuttles, the reduction potential of the naphthalene diimide unit is sufficiently positive (-0.68 V) for the process to be compatible with operation in self-assembled monolayers on gold. Incorporating pyridine units into the macrocycle allowed attachment of the shuttles to an acid-terminated self-assembled monolayer of alkane thiols on gold. The molecular shuttle monolayers were characterized by X-ray photoelectron spectroscopy and their electrochemical behavior probed by electrochemical impedance spectroscopy and double-potential step chronoamperometry, which demonstrated that the redox-switched shuttling was maintained in this environment, occurring on the millisecond time scale.

Operation mechanism of a molecular machine revealed using time-resolved vibrational spectroscopy

Not So Random Walk In rotaxanes, a molecular ring can shuttle back and forth between docking sites along an axle. Panman et al. (p. 1255) traced the intricacies of this shuttling motion using vibrational spectroscopy. The kinetics were dominated by the slow scission of hydrogen bonds tying the ring to its starting site. Varying the length of the axle allowed the extraction of relative rates for forward and backward motion once the ring was free: Somewhat surprisingly, forward motion toward the destination site was slightly hindered relative to regression toward the starting place. Measuring the travel of a molecular ring along an axle explains its shuttling motion. Rotaxanes comprise macrocycles that can shuttle between docking stations along an axle. We explored the nanosecond shuttling mechanism by reversing the relative binding affinities of two stations through ultraviolet-induced transient reduction. We monitored the ensuing changes in the CO-stretching bands of the two stations and the shuttling macrocycle by means of an infrared probing pulse. Because hydrogen-bond scission and formation at the initial and final stations led to well-resolved changes in the respective CO-stretch frequencies, the departure and arrival of the macrocycle could be observed separately. We found that the shuttling involves two steps: thermally driven escape from the initial station, followed by rapid motion along the track ending either at the initial or final station. By varying the track’s length, we found that the rapid motion approximates a biased one-dimensional random walk. However, surprisingly, the direction of the overall motion is opposite that of the bias.

Photochemistry: lighting up nanomachines.

A cleverly engineered molecule uses light to generate a charge-separated state and so cause one of its components to move. Its the latest study of a molecular machine that exploits natures most plentiful energy source.

Conformational Control of Energy Transfer: A Mechanism for Biocompatible Nanocrystal-Based Sensors†

of energy transfer between the NC and an appended species. The analyte concentration is reported by a ratiometric fluorescence signal that is quantifiable and robust across a variety of imaging conditions, allowing for the highresolution measurement of pH within individual endosomes in HeLa cells. This study thus exemplifies the strategy of disconnecting sensing and reporting functions to create a universal fluorescent sensor design that addresses many of the challenges associated with harnessing the unique optical properties of NCs. Several intrinsic properties serve to make NC fluorophores useful for advanced imaging applications, [2] such as intravital multi-photon laser scanning microscopy, multiplexing, and single-receptor tracking. [3] In particular, their narrow and tunable emission spectra, high quantum yields, broad absorption profiles, high photostability, and large single and multi-photon cross sections have made NCs useful complements to organic fluorophores and fluorescent proteins. These attributes provide strong motivation for finding ways to incorporate NCs into fluorescent sensors. Fluorescent sensors with the optical properties of NCs will enable the noninvasive quantification of biochemical species with high spatial and temporal resolution and with the ability to track changes over extended periods of time within complex living environments. [4] One of the most promising concepts for constructing NC sensors is to attach a second chromophore (such as an organic dye or a transition-metal complex) that can act as a fluorescence resonant energy transfer (FRET) partner with the NC. [5] NC fluorophores make ideal FRET donors—their narrow emission features can easily be tuned to match the absorption spectrum of any acceptor, thus endowing the sensing construct with the favorable optical properties of the

Induction of Motion in a Synthetic Molecular Machine: Effect of Tuning the Driving Force

Rotaxane molecular shuttles were studied in which a tetralactam macrocyclic ring moves between a succinamide station and a second station in which the structure is varied. Station 2 in all cases is an aromatic imide, which is a poor hydrogen-bond acceptor in the neutral form, but a strong one when reduced with one or two electrons. When the charge density on the hydrogen-bond-accepting carbonyl groups in station 2 is reduced by changing a naphthalimide into a naphthalene diimide radical anion, the shuttling rate changes only slightly. When station 2 is a pyromellitimide radical anion, however, the shuttling rate is significantly reduced. This implies that the shuttling rate is not only determined by the initial unbinding of the ring from the first station, as previously supposed. An alternative reaction mechanism is proposed in which the ring binds to both stations in the transition state.

Dynamic Covalent Nanoparticle Building Blocks.

Abstract Rational and generalisable methods for engineering surface functionality will be crucial to realising the technological potential of nanomaterials. Nanoparticle‐bound dynamic covalent exchange combines the error‐correcting and environment‐responsive features of equilibrium processes with the stability, structural precision, and vast diversity of covalent chemistry, defining a new and powerful approach for manipulating structure, function and properties at nanomaterial surfaces. Dynamic covalent nanoparticle (DCNP) building blocks thus present a whole host of possibilities for constructing adaptive systems, devices and materials that incorporate both nanoscale and molecular functional components. At the same time, DCNPs have the potential to reveal fundamental insights regarding dynamic and complex chemical systems confined to nanoscale interfaces.

Successive translocation of the rings in a [3]rotaxane

A [2]rotaxane, a [3]rotaxane and the corresponding thread containing two succinamide (succ) binding stations and a central redox-active pyromellitimide (pmi) station were studied. Infrared spectroelectrochemical experiments revealed the translocation of the macrocycle between the succinamide station and the electrochemically reduced pmi station (radical anion and dianion). Remarkably, in the [3]rotaxane, the rings can be selectively translocated. One-electron reduction leads to the translocation of one of the two macrocycles from the succinamide to the pyromellitimide station, whereas activation of the shuttle through two-electron reduction results in the translocation of both macrocycles: the dianion, due to its higher electron density and hence greater hydrogen-bond accepting affinity, is hydrogen bonded to both macrocycles. Systems with such an on-command contraction are known as molecular muscles. The relative strengths of the binding between the macrocycle and the imide anions could be estimated from the hydrogen-bond-induced shifts in the C=O stretching frequencies of hydrogen-bond accepting amide groups of the macrocycle.

In trap fragmentation and optical characterization of rotaxanes

The first experiments on trapped rotaxanes are presented, combining collision induced fragmentation and in-trap laser spectroscopy. The intrinsic optical properties of three rotaxanes and their non-interlocked building blocks (thread and macrocycle) isolated in a quadrupolar ion trap are investigated. The excitation and relaxation processes under thermal activation as well as under photo-activation are addressed. The light and collision induced fragmentation pathways show that the degradation mechanisms occurring in the rotaxane are highly dependent on the nature of the thread. In the prospective of operating photoswitchable molecules, photo-activation is achieved in a controlled way by depositing photo-energy in the desired sub-unit of a mechanically interlocked structure.