light-driven-molecular-motors-on-surfaces-for-single-molecular-imaging

Light-driven Molecular Motors on Surfaces for Single Molecular Imaging

The design and synthesis of a synthetic system that aims for the direct visualization of a synthetic rotary motor at the single molecule level on surfaces ...

University of Groningen

Synthetic light-driven rotary molecular motors show complicated structural dynamics during the rotation process. A combination of DFT calculations and various spectroscopic techniques is employed to study the effect of the bridging group in the lower half of the molecule on the conformational dynamics. It was found that the extent to which the bridging group can accommodate the increased folding in the transition state is the main factor in rationalizing the differences in barrier height and, as a consequence, the rotary speed. These findings will be essential in designing future rotary molecular motors. 

Structural dynamics of overcrowded alkene-based molecular motors during thermal isomerization.

A detailed understanding of the operation and efficiency of unidirectional photomolecular rotary motors is essential for their effective exploitation in molecular nanomachines. Unidirectional motion relies on light-driven conversion from a stable (1 a) to a metastable (1 b) conformation, which then relaxes through a thermally driven helix inversion in the ground state. The excited-state surface has thus far only been experimentally characterised for 1 a. Here we probe the metastable, 1 b, excited state, utilising ultrafast transient absorption and femtosecond stimulated Raman spectroscopy. These reveal that the "dark" excited-state intermediate between 1 a and 1 b has a different lifetime and structure depending on the initial ground-state conformation excited. This suggests that the reaction coordinate connecting 1 a to 1 b differs to that for the reverse photochemical process. The result is contrasted with earlier calculations.

Mapping the Excited-State Potential Energy Surface of a Photomolecular Motor.

The field of synthetic molecular machines has quickly evolved in recent years, growing from a fundamental curiosity to a highly active field of chemistry. Many different applications are being explored in areas such as catalysis, self-assembled and nanostructured materials, and molecular electronics. Rotary molecular motors hold great promise for achieving dynamic control of molecular functions as well as for powering nanoscale devices. However, for these motors to reach their full potential, many challenges still need to be addressed. In this paper we focus on the design principles of rotary motors featuring a double-bond axle and discuss the major challenges that are ahead of us. Although great progress has been made, further design improvements, for example in terms of efficiency, energy input, and environmental adaptability, will be crucial to fully exploit the opportunities that these rotary motors offer.

Molecular rotary motors: Unidirectional motion around double bonds.

The design of a multicomponent system that aims at the direct visualization of a synthetic rotary motor at the single molecule level on surfaces is presented. The synthesis of two functional motors enabling photochemical rotation and fluorescent detection is described. The light-driven molecular motor is found to operate in the presence of a fluorescent tag if a rigid long rod (32 Å) is installed between both photoactive moieties. The photochemical isomerization and subsequent thermal helix inversion steps are confirmed by H NMR and UV-vis absorption spectroscopies. In addition, the tetra-acid functioned motor can be successfully grafted onto amine-coated quartz and it is shown that the light responsive rotary motion on surfaces is preserved.

Design, Synthesis, and Isomerization Studies of Light-Driven Molecular Motors for Single Molecular Imaging.

Stimuli-controlled motion at the molecular level has fascinated chemists already for several decades. Taking inspiration from the myriad of dynamic and machine-like functions in nature, a number of strategies have been developed to control motion in purely synthetic systems. Unidirectional rotary motion, such as is observed in ATP synthase and other motor proteins, remains highly challenging to achieve. Current artificial molecular motor systems rely on intrinsic asymmetry or a specific sequence of chemical transformations. Here, we present an alternative design in which the rotation is directed by a chiral guest molecule, which is able to bind non-covalently to a light-responsive receptor. It is demonstrated that the rotary direction is governed by the guest chirality and hence, can be selected and changed at will. This feature offers unique control of directional rotation and will prove highly important in the further development of molecular machinery.

Supramolecularly directed rotary motion in a photoresponsive receptor.

The highly regio- and enantioselective (up to >99:1 dr, up to 99:1 er) desymmetrization of meso-1,4-dibromocycloalk-2-enes using asymmetric allylic substitution with organolithium reagents to afford enantioenriched bromocycloalkenes (ring size of 5 to 7) has been achieved. The cycloheptene products undergo an unusual ring contraction. The synthetic versatility of this Cu(I)-catalyzed reaction is demonstrated by the concise stereocontrolled preparation of cyclic amino alcohols, which are privileged chiral structures in natural products and pharmaceuticals and widely used in synthesis and catalysis.

Desymmetrization of meso-Dibromocycloalkenes through Copper(I)-Catalyzed Asymmetric Allylic Substitution with Organolithium Reagents.

A multiphotochromic hybrid system is presented in which a light-driven overcrowded alkene-based molecular rotary motor is connected to a dithienylethene photoswitch. Ring closing of the dithienylethene moiety, using an irradiation wavelength different from the wavelength applied to operate the molecular motor, results in inhibition of the rotary motion as is demonstrated by detailed  H-NMR and UV/Vis experiments. For the first time, a light-gated molecular motor is thus obtained. Furthermore, the excitation wavelength of the molecular motor is red-shifted from the UV into the visible-light region upon attachment of the dithienylethene switch.

Light-Gated Rotation in a Molecular Motor Functionalized with a Dithienylethene Switch.

The direct carbolithiation of diphenylacetylenes and their cross-coupling procedure taking advantage of the intermediate alkenyllithium reagents are presented. By employing our recently discovered highly active palladium nanoparticle based catalyst, we were able to couple an alkenyllithium reagent with a high (Z/E) selectivity (10 : 1) and good yield to give the breast cancer drug tamoxifen in just 2 steps from commercially available starting materials and with excellent atom economy and reaction mass efficiency.

An atom efficient synthesis of tamoxifen.

DNA-peptide interactions are involved in key life processes, including DNA recognition, replication, transcription, repair, organization, and modification. Development of tools that can influence DNA-peptide binding non-invasively with high spatiotemporal precision could aid in determining its role in cells and tissues. Here, the design, synthesis, and study of photocontrolled tools for sequence-specific small peptide-DNA major and minor groove interactions are reported, shedding light on DNA binding by transcriptionally active peptides. In particular, photoswitchable moieties were implemented in the peptide backbone or turn region. In each case, DNA binding was affected by photochemical isomerization, as determined in fluorescent displacement assays on model DNA strands, which provides promising tools for DNA modulation.

Comparative Study of Photoswitchable Zinc-Finger Domain and AT-Hook Motif for Light-Controlled Peptide-DNA Binding.

A general one-pot procedure for the 1,2-addition of organolithium reagents to amides followed by the Buchwald-Hartwig amination with in situ released lithium amides is presented. In this work amides are used as masked ketones, revealed by the addition of organolithium reagents which generates a lithium amide, suitable for subsequent Buchwald-Hartwig coupling in the presence of a palladium catalyst. This methodology allows for rapid, efficient and atom economic synthesis of aminoarylketones in good yields.

Article	Year
Structural dynamics of overcrowded alkene-based molecular motors during thermal isomerization. The Journal of organic chemistry\| PubMed ID: 24410498	2014
Mapping the Excited-State Potential Energy Surface of a Photomolecular Motor. Angewandte Chemie (International ed. in English)\| PubMed ID: 29633492	2018
Molecular rotary motors: Unidirectional motion around double bonds. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 29712825	2018
Design, Synthesis, and Isomerization Studies of Light-Driven Molecular Motors for Single Molecular Imaging. The Journal of organic chemistry\| PubMed ID: 29741383	2018
Supramolecularly directed rotary motion in a photoresponsive receptor. Nature communications\| PubMed ID: 29777101	2018
Desymmetrization of meso-Dibromocycloalkenes through Copper(I)-Catalyzed Asymmetric Allylic Substitution with Organolithium Reagents. Journal of the American Chemical Society\| PubMed ID: 29790736	2018
Light-Gated Rotation in a Molecular Motor Functionalized with a Dithienylethene Switch. Angewandte Chemie (International ed. in English)\| PubMed ID: 29806875	2018
An atom efficient synthesis of tamoxifen. Organic & biomolecular chemistry\| PubMed ID: 30724943	2019
Comparative Study of Photoswitchable Zinc-Finger Domain and AT-Hook Motif for Light-Controlled Peptide-DNA Binding. Chemistry (Weinheim an der Bergstrasse, Germany)\| PubMed ID: 30735272	2019
One-pot, modular approach to functionalized ketones via nucleophilic addition/Buchwald-Hartwig amination strategy. Chemical communications (Cambridge, England)\| PubMed ID: 30785130	2019

Ben L. Feringa

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