Design rules for optimization of photophysical and kinetic properties of azoarene photoswitches.

Azoarenes are an important class of molecular photoswitches that often undergo → isomerization with ultraviolet light and have short -isomer lifetimes. Azobenzene has been a widely studied photoswitch for decades but can be poorly suited for photopharmacological applications due to its UV-light absorption and short-lived -isomer half-life (). Recently, diazo photoswitches with one or more thiophene rings in place of a phenyl ring have emerged as promising candidates, as they exhibit a stable photostationary state (98% → conversion) and -isomer absorption () in the visible light range (405 nm). In this work, we performed density functional theory calculations [PBE0-D3BJ/6-31+G(d,p)] on 26 -azothiophenes, substituted with one phenyl ring and one thiophene ring on the diazo bond. We calculated the -isomer absorption () and -isomer for a set of 26 -azothiophenes. We compared their properties to thiophene-based photoswitches that have been studied previously. We separated the 26 proposed photoswitches into four quadrants based on their and relative to past generations of -azothiophene photoswitches. We note 8 -azothiophenes with redshifted and longer than previous systems. Our top candidate has and a approaching 360 nm and 279 years, respectively. The results here present a pathway towards leveraging and optimizing two properties of photoswitches previously thought to be inversely related.