Systematic modifications of substitution patterns for property tuning of photoswitchable asymmetric azobenzenes

Abstract

Suitable designed photoswitches based on azobenzenes are essential structural features for photopharmacological compounds. Optimized azobenzenes are important for serving as building blocks in “azo extension” strategies, and for designing photodrugs with tailored properties. Herein we present the synthesis and characterization of a variety of asymmetric azobenzenes by addressing selected structural features of the diazene core, such as polarity, steric demand, and electronic properties. Systematic exploration led to photoswitches with a relaxation half-life of seconds, minutes, hours, or days. Furthermore, the influence of different substitution patterns on the photophysical properties was charted. For analysis of all switches, robust characterization as well as examination under near-to physiological conditions was established, in order to assist with photoswitch choice for specific biological applications.