Anouk S. Lubbe

Control of Rotor Function in Light-Driven Molecular Motors

A study is presented on the control of rotary motion of an appending rotor unit in a light-driven molecular motor. Two new light driven molecular motors were synthesized that contain aryl groups connected to the stereogenic centers. The aryl groups behave as bidirectional free rotors in three of the four isomers of the 360° rotation cycle, but rotation of the rotors is hindered in the fourth isomer. Kinetic studies of both motor and rotor functions of the two new compounds are given, using (1)H NMR, 2D-EXSY NMR, and UV-vis spectroscopy. In addition, we present the development of a new method for introducing a range of aryl substituents at the α-carbon of precursors for molecular motors. The present study shows how the molecular system can be photochemically switched between a state of free rotor rotation and a state of hindered rotation and reveals the dynamics of coupled rotary systems.

Asymmetric Synthesis of First Generation Molecular Motors

A general enantioselective route to functionalized first generation molecular motors is described. An enantioselective protonation of the silyl enol ethers of indanones by a Au(I)BINAP complex sets the stage for a highly diastereoselective McMurry coupling as a second enhancement step for enantiomeric excess. In this way various functionalized overcrowded alkenes could be synthesized in good yields (up to 78%) and good to excellent enantiomeric excess (85% ee->98% ee) values.

On the Role of Viscosity in the Eyring Equation

Transition-state theory allows for the characterization of kinetic processes in terms of enthalpy and entropy of activation by using the Eyring equation. However, for reactions in solution, it fails to take the change of viscosity of solvents with temperature into account. A second-generation unidirectional rotary molecular motor was used as a probe to study the effects of temperature-dependent viscosity changes upon unimolecular thermal isomerization processes. By combining the free-volume model with transition-state theory, a modified version of the Eyring equation was derived, in which the rate is expressed in terms of both temperature and viscosity.

Photoswitching of DNA Hybridization Using a Molecular Motor

Reversible control over the functionality of biological systems via external triggers may be used in future medicine to reduce the need for invasive procedures. Additionally, externally regulated biomacromolecules are now considered as particularly attractive tools in nanoscience and the design of smart materials, due to their highly programmable nature and complex functionality. Incorporation of photoswitches into biomolecules, such as peptides, antibiotics, and nucleic acids, has generated exciting results in the past few years. Molecular motors offer the potential for new and more precise methods of photoregulation, due to their multistate switching cycle, unidirectionality of rotation, and helicity inversion during the rotational steps. Aided by computational studies, we designed and synthesized a photoswitchable DNA hairpin, in which a molecular motor serves as the bridgehead unit. After it was determined that motor function was not affected by the rigid arms of the linker, solid-phase synthesis was employed to incorporate the motor into an 8-base-pair self-complementary DNA strand. With the photoswitchable bridgehead in place, hairpin formation was unimpaired, while the motor part of this advanced biohybrid system retains excellent photochemical properties. Rotation of the motor generates large changes in structure, and as a consequence the duplex stability of the oligonucleotide could be regulated by UV light irradiation. Additionally, Molecular Dynamics computations were employed to rationalize the observed behavior of the motor–DNA hybrid. The results presented herein establish molecular motors as powerful multistate switches for application in biological environments.

Molecular Motors in Aqueous Environment

Molecular motors are Nature’s solution for (supra)molecular transport and muscle functioning and are involved in most forms of directional motion at the cellular level. Their synthetic counterparts have also found a myriad of applications, ranging from molecular machines and smart materials to catalysis and anion transport. Although light-driven rotary molecular motors are likely to be suitable for use in an artificial cell, as well as in bionanotechnology, thus far they are not readily applied under physiological conditions. This results mainly from their inherently aromatic core structure, which makes them insoluble in aqueous solution. Here, the study of the dynamic behavior of these motors in biologically relevant media is described. Two molecular motors were equipped with solubilizing substituents and studied in aqueous solutions. Additionally, the behavior of a previously reported molecular motor was studied in micelles, as a model system for the biologically relevant confined environment. Design principles were established for molecular motors in these media, and insights are given into pH-dependent behavior. The work presented herein may provide a basis for the application of the remarkable properties of molecular motors in more advanced biohybrid systems.

Artificial microtubules burst with energy

Among the multitude of biological machines that nature employs to keep the cell operational, molecular motor proteins are certainly among the most captivating. These proteins convert chemical energy into mechanical work and drive most forms of motion (1). Cytoplasmic motors, for example, are proteins that move along a track and can transport cargo or induce muscle contraction. Beside these types of linear motion, rotary motion is ubiquitous. It occurs, for example, in flagella, which propel bacteria, or in ATP synthase, the protein that creates ATP. Alternatively, polymerization motors, such as actin filaments or microtubules, generate force by their assembly or disassembly. To understand the dynamics of the living cell, as well as to create increasingly complex artificial systems, chemists strive to construct artificial molecular motors and machines. In PNAS, Fredy et al. (2) present an innovative design that combines molecular motion with supramolecular chemistry to build a light-powered self-assembled machine in which energy is accumulated and released. This induces a mechanical effect that mimics the pulling force of microtubule disassembly. Synthetic molecular machines of increasing sophistication have been built and studied for several decades (3). Analogous to molecular motors found in nature, they are defined as molecules that can convert an energy input, typically in the form of chemical fuel or light, into translational or rotational motion. To harvest this output for mechanical work remains a fundamental challenge as molecular machines usually operate in solution. At the molecular scale, Brownian movement and viscous forces dominate, while the influence of gravity and inertia is negligible. Any force generated by a … [↵][1]1To whom correspondence should be addressed. Email: b.l.feringa{at}rug.nl. [1]: #xref-corresp-1-1