Computational Rational Design of Bridgehead Nitrogen Heterocyclic Azobenzene Photoswitches

Azobenzenes are proven to be one of the most successful molecular photoswitches applied across different fields such as organic chemistry, materials science, cosmetics, and pharmaceuticals. Such a widespread implementation is possible because of their photochromic properties contingent upon the substitution pattern and aryl-core nature. In recent endeavors of molecular design, replacing one or both phenyl rings with heteroaromatics turned out to be a good strategy to access compounds with improved photoswitching properties, as well as to expand molecular diversity. One of the challenges related to the design of new azobenzene photoswitches is that it often includes the synthesis of large libraries of compounds due to limited methods for prediction of their properties. Herein, we present a computationally driven workflow for the design and synthesis of a novel class of azobenzene photoswitches, heteroaryl azobenzenes with N-bridgehead heterocycles─pyrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine. A small library of heteroaryl photoswitches was synthesized, and their photochemical properties were evaluated. Subsequently, these results were used to validate a computational approach, which included the in silico evaluation of a large library of designed photoswitch candidates leading to the synthesis of a new photoswitch with improved spectral properties, red-shifted λ_max values.