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

Azoarenes are an important class of molecular photoswitches that often undergo E -> Z isomerization with ultraviolet light and have short Z-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 Z-isomer half-life (t1/2). 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% E -> Z conversion) and E-isomer absorption (lambda max) 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 hemi-azothiophenes, substituted with one phenyl ring and one thiophene ring on the diazo bond. We calculated the E-isomer absorption (lambda max) and Z-isomer t1/2 for a set of 26 hemi-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 lambda max and t1/2 relative to past generations of hemi-azothiophene photoswitches. We note 8 hemi-azothiophenes with redshifted lambda max and longer t1/2 than previous systems. Our top candidate has lambda max and a t1/2 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. The E-isomer lambda max and Z-isomer t1/2 have been simultaneously optimized for a set of 26 hemi-azothiophenes. We found that by incorporating cross-conjugated thiophenes and additional pi-conjugation, these two properties can be leveraged.