Photoswitching of Diazocines in Aqueous Media.

We present a systematic investigation of the photophysical properties of diazocines in aqueous media. The Z-E photoconversion yields of CH2CH2- and CH2S-bridged diazocines decrease with increasing water content in acetonitrile. However, there is one exception. A CH2-NAc-bridged diazocine mostly retains its photostationary state in water (85 to 72%) because of the high quantum yields for the Z → E conversion. Moreover, it is water-soluble without further substitution and is therefore ideally suited as a photoswitch in biological (aqueous) environments.

Efficient Conversion of Light to Chemical Energy: Directional, Chiral Photoswitches with Very High Quantum Yields.

Photochromic systems have been used to achieve a number of engineering functions such as light energy conversion, molecular motors, pumps, actuators, and sensors. Key to practical applications is a high efficiency in the conversion of light to chemical energy, a rigid structure for the transmission of force to the environment, and directed motion during isomerization. We present a novel type of photochromic system (diindane diazocines) that converts visible light with an efficiency of 18 % to chemical energy. Quantum yields are exceptionally high with >70 % for the cis-trans isomerization and 90 % for the back-reaction and thus higher than the biochemical system rhodopsin (64 %). Two diastereomers (meso and racemate) were obtained in only two steps in high yields. Both isomers are directional switches with high conversion rates (76-99 %). No fatigue was observed after several thousands of switching cycles in both systems.

Visible-light-driven photocontrol of the Trp-cage protein fold by a diazocine cross-linker.

Diazocines are characterized by extraordinary photochemical properties rendering them of particular interest for switching the conformation of biomolecules with visible light. Current developments afford synthetic access to unprecedented diazocine derivatives promising particular opportunities in photocontrol of proteins and biological systems. In this work, the well-established approach of photocontrolling the secondary structure of α-helices was exploited using a diazocine to reversibly fold and unfold the tertiary structure of a small protein. The protein of choice was the globulary folded Trp-cage, a widely used model system for the elucidation of protein folding pathways. A specifically designed, short and rigid dicarboxy-functionalized diazocine-based cross-linker was attached to two solvent-exposed side chains at the α-helix of the miniprotein through the use of a primary amine-selective active ester. This cross-linking strategy is orthogonal to the common cysteine-based chemistry. The cross-linked Trp-cage was successfully photoisomerized and exhibited a strong correlation between protein fold and diazocine isomeric state. As determined by NMR spectroscopy, the cis-isomer stabilized the fold, while the trans-isomer led to complete protein unfolding. The successful switching of the protein fold in principle demonstrates the ability to control protein function, as the activity depends on their structural integrity.

Synthetic Photoswitchable Neurotransmitters Based on Bridged Azobenzenes.

Photoswitchable neurotransmitters of ionotropic kainate receptors were synthesized by tethering a glutamate moiety to disubstituted C2-bridged azobenzenes, which were prepared through a novel methodology that allows access to diazocines with higher yields and versatility. Because of the singular properties of these photochromes, photoisomerizable compounds were obtained with larger thermal stability for their inert cis isomer than for their biologically activity trans state. This enabled selective neuronal firing upon irradiation without background activity in the dark.

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials.

Seven symmetrically 3,3'-substituted diazocines were synthesized. Functional groups include alcohol, azide, amine and vinyl groups, which are suitable for polymer synthesis. Upon irradiation at 385 and 530 nm the diazocines perform a reversible, pincer-type movement switching the 3,3'-distance between 6.1 Å (cis, stable isomer) and 8.2 Å (trans, metastable isomer). Key reactions in the synthesis are an oxidative C-C coupling of 2-nitrotoluenes (75-82% yield) and a reductive ring closure to form the diazocines (56-60% yield). The cyclization of the dinitro compound to the azo compound was improved in yield and reproducibility, by over-reduction to the hydrazine and reoxidation to the azo unit. In contrast to 3,3'- and 4,4'-diaminodiazocine, which have been implemented in macromolecules for conformation switching, our compounds exhibit improved photophysical properties (photostationary states, separation of absorption bands in the cis and trans configuration). Hence they are promising candidates as molecular switches in photo and mechanoresponsive macromolecules and other smart materials.