Directionality Reversal and Shift of Rotational Axis in a Hemithioindigo Macrocyclic Molecular Motor.

Molecular motors are central driving units for nanomachinery, and control of their directional motions is of fundamental importance for their functions. Light-driven variants use easy to provide, easy to dose, and waste-free fuel with high energy content, making them particularly interesting for applications. Typically, light-driven molecular motors work via rotations around dedicated chemical bonds where the directionality of the rotation is dictated by the steric effects of asymmetry in close vicinity to the rotation axis. In this work, we show how unidirectional rotation around a virtual axis can be realized by reprogramming a molecular motor. To this end, a classical light-driven motor is restricted by macrocyclization, and its intrinsic directional rotation is transformed into a directional rotation of the macrocyclic chain in the opposite direction. Further, solvent polarity changes allow to toggle the function of this molecular machine between a directional motor and a nondirectional photoswitch. In this way, a new concept for the design of molecular motors is delivered together with elaborate control over their motions and functions by simple solvent changes. The possibility of sensing the environmental polarity and correspondingly adjusting the directionality of motions opens up a next level of control and responsiveness to light-driven nanoscopic motors.

Light-Controlled Cell-Cycle Arrest and Apoptosis.

Cell-cycle interference by small molecules has widely been used to study fundamental biological mechanisms and to treat a great variety of diseases, most notably cancer. However, at present only limited possibilities exist for spatio-temporal control of the cell cycle. Here we report on a photocaging strategy to reversibly arrest the cell cycle at metaphase or induce apoptosis using blue-light irradiation. The versatile proteasome inhibitor MG132 is photocaged directly at the reactive aldehyde function effectively masking its biological activity. Upon irradiation reversible cell-cycle arrest in the metaphase is demonstrated to take place in vivo. Similarly, apoptosis can efficiently be induced by irradiation of human cancer cells. With the developed photopharmacological approach spatio-temporal control of the cell cycle is thus enabled with very high modulation, as caged MG132 shows no effect on proliferation in the dark. In addition, full compatibility of photo-controlled uncaging with dynamic microscopy techniques in vivo is demonstrated. This visible-light responsive tool should be of great value for biological as well as medicinal approaches in need of high-precision targeting of the proteasome and thereby the cell cycle and apoptosis.

Active and Unidirectional Acceleration of Biaryl Rotation by a Molecular Motor.

Light-driven molecular motors possess immense potential as central driving units for future nanotechnology. Integration into larger molecular setups and transduction of their mechanical motions represents the current frontier of research. Herein we report on an integrated molecular machine setup allowing the transmission of potential energy from a motor unit onto a remote receiving entity. The setup consists of a motor unit connected covalently to a distant and sterically encumbered biaryl receiver. By action of the motor unit, single-bond rotation of the receiver is strongly accelerated and forced to proceed unidirectionally. The transmitted potential energy is directly measured as the extent to which energy degeneration is lifted in the thermal atropisomerization of this biaryl. Energy degeneracy is reduced by more than 1.5 kcal mol-1 , and rate accelerations of several orders of magnitude in terms of the rate constants are achieved.

Transmission of Unidirectional Molecular Motor Rotation to a Remote Biaryl Axis.

Molecular motors undergo repetitive directional motions upon external energy input. A profound challenge is the defined transfer of directional motor motions to remote entities at the molecular scale. Herein, we present a molecular setup that allows for the transfer of the directional rotation of a light-powered motor unit onto a remote biaryl axis via an ethylene glycol chain link. Based on a combination of X-ray crystallographic analysis, ECD, and NMR experiments as well as a comprehensive theoretical assessment, we provide evidence for the coupled stepwise directional motions of both molecular units. With the presented setup, facile integration of molecular motor units into larger functional frameworks and complex molecular machines can be explored consciously in the future.

Photocontrol of Polar Aromatic Interactions by a Bis-Hemithioindigo Based Helical Receptor.

The first example of a bis-hemithioindigo (bis-HTI)-based molecular receptor was realized. Its folding and selective binding affinity for aromatic guest molecules can be precisely controlled by visible light and heat. The thermodynamically stable state of the bis-HTI is the s-shaped planar Z,Z-configuration. After irradiation with 420 nm light only the E,Z-configuration is formed in a highly selective photoisomerization. The E,Z-isomer adopts a helical conformation because of the implementation of repulsive steric interactions. The E,Z-configured helix is able to recognize electron-poor aromatic guests exclusively through polar aromatic interactions and also distinguishes between regioisomers. After heating, the Z,Z-configuration is completely restored and the aromatic guest molecule is efficiently released.