High‐Throughput Optimization of Photochemical Reactions using Segmented‐Flow Nanoelectrospray‐Ionization Mass Spectrometry**

Abstract

AbstractWithin the realm of drug discovery, high‐throughput experimentation techniques enable the rapid optimization of reactions and expedited generation of drug compound libraries for biological and pharmacokinetic evaluation. Herein we report the development of a segmented flow mass spectrometry‐based platform to enable the rapid exploration of photoredox reactions for early‐stage drug discovery. Specifically, microwell plate‐based photochemical reaction screens were reformatted to segmented flow format to enable delivery to nanoelectrospray ionization‐mass spectrometry analysis. This approach was demonstrated for the late‐stage modification of complex drug scaffolds, as well as the subsequent structure–activity relationship evaluation of synthesized analogs. This technology is anticipated to expand the robust capabilities of photoredox catalysis in drug discovery by enabling high‐throughput library diversification.