Azobenzene is the prototypical photoswitch; its photophysical and energy-storing properties are well-known, and it can be readily synthesized. Azoarenes have been used for applications in materials science and photopharmacology. Azoarene photoswitches are a general class of azobenzene derivatives that offer considerable structural diversity and undergo light-promoted E➝Z isomerizations when irradiated with ultraviolet to infrared light. Recent efforts in the field have focused on heteroarenes such as pyrazoles and thiophenes, because of their red-shifted absorption maximum (λ max ) and promising band separation in the E-and Zisomers. There has been a broad effort to red-shift the absorption maximum (λ max ) of the azobenzene E-isomer (λ max = 320 nm) into the visible-light range to minimize photodamage in living organisms. This is especially true in photopharmacology, where the half-life (t 1/2 ) of the metastable Z-isomer needs to be on the order of days to establish a stable photostationary state. In 2019, Fuchter and co-workers synthesized a series of hemi-azopyrazole photoswitches showing UV-promoted photoswitching (80-93% Z-isomer population) and long-lived Z-isomer t 1/2 (up to 46 years). In 2021, a set of bis-azopyrazoles discovered by Li and co-workers exhibited nearly complete E➝Z photoconversion (94-98%) and a Z-isomer t 1/2 of up to 681 days. Our group recently reported the results of a high-throughput virtual screening (HTVS) where we observed significant differences in the λ max and t 1/2 values for a set of positional isomers of bis-azofurans and bisazothiophenes. We showed that isomeric bis-azothiophenes and bis-diazofurans (2,2 vs. 3,3) increased the λ max of the Eisomers by as much as 77 nm while simultaneously lowering the t 1/2 by six orders of magnitude. These changes resulted from the cross-conjugation vs. π-conjugation significantly increasing the activation free energies (∆𝐺 ‡ ) and shorter λ max wavelengths for the (3,3) isomers.