Cross-conjugation controls the stabilities and photophysical properties of heteroazoarene photoswitches.

Azoarene photoswitches are versatile molecules that interconvert from their E -isomer to their Z -isomer with light. Azobenzene is a prototypical photoswitch but its derivatives can be poorly suited for in vivo applications such as photopharmacology due to undesired photochemical reactions promoted by ultraviolet light and the relatively short half-life ( t 1/2 ) of the Z -isomer (2 days). Experimental and computational studies suggest that these properties ( λ max of the E isomer and t 1/2 of the Z -isomer) are inversely related. We identified isomeric azobisthiophenes and azobisfurans from a high-throughput screening study of 1540 azoarenes as photoswitch candidates with improved λ max and t 1/2 values relative to azobenzene. We used density functional theory to predict the activation free energies and vertical excitation energies of the E - and Z -isomers of 2,2- and 3,3-substituted azobisthiophenes and azobisfurans. The half-lives depend on whether the heterocycles are π-conjugated or cross-conjugated with the diazo π-bond. The 2,2-substituted azoarenes both have t 1/2 values on the scale of 1 hour, while the 3,3-analogues have computed half-lives of 40 and 230 years (thiophene and furan, respectively). The 2,2-substituted heteroazoarenes have significantly higher λ max absorptions than their 3,3-substituted analogues: 76 nm for azofuran and 77 nm for azothiophene.