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

Within 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.

Automated summary

In the field of drug discovery, high-throughput experimentation techniques are used to optimize reactions and generate drug compound libraries quickly for evaluation. This study presents a segmented flow mass spectrometry-based platform to explore photoredox reactions in early-stage drug discovery. The technology enables fast analysis of photochemical reactions and evaluation of synthesized analogs, expanding the capabilities of photoredox catalysis in drug discovery.