Synthesis and Development of Inverse-Type Nucleoside Diarylethene Photoswitches.

Nucleosidic diarylethenes (DAEs) have evolved from an emerging class of photochromes into a well-established option for integrating photochromic functionalities into biological systems. However, a comprehensive understanding of how chemical structure influences their photochromic properties remains essential. While structural features, such as an inverse connection between the aryl residues and the ethene bridge, are well-documented for classical DAEs, their application to nucleosidic DAEs has been underexplored. In this study, we address this gap by developing three distinct types of inverse nucleosidic DAEs - semi-inverse thiophenes, semi-inverse uridines and inverse uridines. We successfully synthesized these compounds and conducted comprehensive analyses of their photostationary states, thermal stability, reversibility, and reaction quantum yields. Additionally, we conducted an in-depth comparison of their photochromic properties with those of their normal-type counterparts. Among the synthesized compounds, seven semi-inverse thiophenes exhibited the most promising characteristics. Notably, these compounds demonstrated excellent fatigue resistance, with up to 96% retention of photochromic activity over 40 switching cycles, surpassing the performance of all comparable nucleosidic DAEs reported to date. These findings hold significant promise for future applications in various fields.

A DNA-Based Two-Component Excitonic Switch Utilizing High-Performance Diarylethenes.

Nucleosidic diarylethenes (DAEs) are an emerging class of photochromes but have rarely been used in materials science. Here, we have developed doubly methylated DAEs derived from 2'-deoxyuridine with high thermal stability and fatigue resistance. These new photoswitches not only outperform their predecessors but also rival classical non-nucleosidic DAEs. To demonstrate the utility of these new DAEs, we have designed an all-optical excitonic switch consisting of two oligonucleotides: one strand containing a fluorogenic double-methylated 2'-deoxyuridine as a fluorescence donor and the other a tricyclic cytidine (tC) as acceptor, which together form a highly efficient conditional Förster-Resonance-Energy-Transfer (FRET) pair. The system was operated in liquid and solid phases and showed both strong distance- and orientation-dependent photochromic FRET. The superior ON/OFF contrast was maintained over up to 100 switching cycles, with no detectable fatigue.

Development of High-Performance Pyrimidine Nucleoside and Oligonucleotide Diarylethene Photoswitches.

Nucleosidic and oligonucleotidic diarylethenes (DAEs) are an emerging class of photochromes with high application potential. However, their further development is hampered by the poor understanding of how the chemical structure modulates the photochromic properties. Here we synthesized 26 systematically varied deoxyuridine- and deoxycytidine-derived DAEs and analyzed reaction quantum yields, composition of the photostationary states, thermal and photochemical stability, and reversibility. This analysis identified two high-performance photoswitches with near-quantitative, fully reversible back-and-forth switching and no detectable thermal or photochemical deterioration. When incorporated into an oligonucleotide with the sequence of a promotor, the nucleotides maintained their photochromism and allowed the modulation of the transcription activity of T7 RNA polymerase with an up to 2.4-fold turn-off factor, demonstrating the potential for optochemical control of biological processes.

Optochemical control of transcription by the use of 7-deaza-adenosine-based diarylethenes.

Out of nine different 7-deaza-adenosine diarylethenes, we identified a high-performance photoswitch, suitable for the synthesis of photochromic DNA. By using solid phase synthesis, a photoresponsive T7 promotor was generated which allowed reversibly modulating the rate of enzymatic RNA synthesis in vitro.

Correction: Optochemical control of transcription by the use of 7-deaza-adenosine-based diarylethenes.

Correction for 'Optochemical control of transcription by the use of 7-deaza-adenosine-based diarylethenes' by Simon M. Büllmann et al., Chem. Commun., 2021, 57, 6596-6599, DOI 10.1039/D1CC02639A.

"Click-switch" - one-step conversion of organic azides into photochromic diarylethenes for the generation of light-controlled systems.

Diarylethenes (DAEs) are an established class of photochromic molecules, but their effective incorporation into pre-existing targets is synthetically difficult. Here we describe a new class of DAEs in which one of the aryl rings is a 1,2,3-triazole that is formed by "click" chemistry between an azide on the target and a matching alkyne-cyclopentene-thiophene component. This late-stage zero-length linking allows for tight integration of the DAE with the target, thereby increasing the chances for photomodulation of target functions. Nineteen different DAEs were synthesized and their properties investigated. All showed photochromism. Electron-withdrawing groups, and in particular -M-substituents at the triazole and/or thiophene moiety resulted in DAEs with high photo- and thermostability. Further, the chemical nature of the cyclopentene bridge had a strong influence on the behaviour upon UV light irradiation. Incorporation of perfluorinated cyclopentene led to compounds with high photo- and thermostability, but the reversible photochromic reaction was restricted to halogenated solvents. Compounds containing the perhydrogenated cyclopentene bridge, on the other hand, allowed the reversible photochromic reaction in a wide range of solvents, but had on average lower photo- and thermostabilities. The combination of the perhydrocyclopentene bridge and electron-withdrawing groups resulted in a DAE with improved photostability and no solvent restriction. Quantum chemical calculations helped to identify the photoproducts formed in halogenated as well as non-halogenated solvents. For two optimized DAE photoswitches, photostationary state composition and reaction quantum yields were determined. These data revealed efficient photochemical ring closure and opening. We envision applications of these new photochromic diarylethenes in photonics, nanotechnology, photobiology, photopharmacology and materials science.

Norbornadiene-bridged diarylethenes and their conversion into turn-off fluorescent photoswitches.

We describe the synthesis and characterization of novel diarylethene photoswitches that contain a norbornadiene bridge and operate as p-type positive photochromes. One of the double bonds of norbornadiene is furthermore utilized to attach a fluoresceine tetrazine by an iEDDA cascade reaction, thereby forming a turn-off mode fluorescent photoswitch.