Organic Chemistry

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 its relatively short half-life (t1/2) of the Z-isomer (2 days). Experimental and computational studies suggest that these properties (位max of the E isomer and t1/2 of the Z-isomer) are inversely related. We identified isomeric azobisthiophenes and azobisfurans from a high-throughput screening study of 1700 azoarenes as photoswitch candidates with improved 位max and t1/2 values relative to azobenzene. We used density functional theory to predict the activation free energies, reaction 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 饾湅-conjugated or cross-conjugated with the diazo 饾湅-bond. The 2,2-substituted azoarenes both have t1/2 values on the scale of 1 hour, while the 3,3-analogues have computed half-lives of 40 (thiophene) and 230 (furan) years. The 2,2-substituted heteroazoarenes have significantly higher 位max absorptions than their 3,3-substituted analogs: 76 nm for azofuran and 77 nm for azothiophene.


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Supporting information containing all optimized reactants, IRC calculations, and transition structures
The compressed folder attached contains all of the optimized output files for all structures used in this publication