Photoswitchable diarylethenes: From molecular structures to biological applications

Diarylethene (DAE) photoswitches, known for their reversible photoinduced cyclization and cycloreversion reactions, have shown great promise in various fields such as optical data storage, optoelectronic devices, supramolecular self-assembly, anti-counterfeiting, chiral photoswitches, and photocontrolled catalysis. Recently, there has been a growing interest in utilizing DAEs as smart triggers to regulate biological events, highlighting their advantages over commonly studied azobenzene switches, including thermal irreversibility, high photoswitching efficiency, favorable cellular stability, and low toxicity. However, a comprehensive review specifically focusing on the biological applications of DAEs has yet to be reported. In this in-depth review, we present key modification strategies aimed at enhancing the photoswitching behavior of DAEs and optimizing their performance for biological applications. These strategies include achieving near-infrared (NIR) photochromism, enhancing aggregation-induced emission (AIE) performance, improving water solubility, enabling fluorescence “turn-on,” increasing cyclization yield, and enabling visible light triggering. Moreover, we highlight recent advancements in the use of DAEs as photoswitches in biological applications, covering areas such as photoswitchable fluorescence sensing and imaging, super-resolution imaging, photoswitchable nucleosides and oligonucleotides, photocontrolled photodynamic therapy, and regulation of biological activity in photopharmacology. Furthermore, we identify the current challenges hindering the bioapplications of DAEs and forecast the development trends of photochromic DAEs for potential biological applications. This comprehensive review aims to inspire further research and innovation in the development of novel DAE derivatives for future in vivo bioapplications.