Abstract
The implementation of continuous flow technology is critical towards enhancing the application of photochemical reactions for industrial process development. However, there are significant time and resource constraints associated with translating discovery scale vial-based batch reactions to continuous flow scale-up conditions. Herein we report the development of a droplet microfluidic platform, which enables high-throughput reaction discovery in flow to generate pharmaceutically relevant compound libraries. This platform allows for enhanced material efficiency, as reactions can be performed on picomole scale. Furthermore, high-throughput data collection via on-line ESI mass spectrometry facilitates the rapid analysis of individual, nanoliter-sized reaction droplets at acquisition rates of 0.3 samples/s. We envision this high-throughput screening platform to expand upon the robust capabilities and impact of photochemical reactions in drug discovery and development.
Highlights
The implementation of continuous flow technology is critical towards enhancing the application of photochemical reactions for industrial process development
While reported High-throughput experimentation (HTE) flow systems have been successfully applied to non-photochemical reactions, demand remains for the development of HTE platforms for screening photochemical reactions in continuous flow
We aimed to develop a system for irradiating droplet samples, followed by in-line dilution and subsequent electrospray ionization-mass spectrometry (ESI-mass spectrometry-based (MS)) analysis (Fig. 1)
Summary
The implementation of continuous flow technology is critical towards enhancing the application of photochemical reactions for industrial process development. We report the development of a droplet microfluidic platform, which enables high-throughput reaction discovery in flow to generate pharmaceutically relevant compound libraries. This platform allows for enhanced material efficiency, as reactions can be performed on picomole scale. High-throughput data collection via on-line ESI mass spectrometry facilitates the rapid analysis of individual, nanoliter-sized reaction droplets at acquisition rates of 0.3 samples/s We envision this high-throughput screening platform to expand upon the robust capabilities and impact of photochemical reactions in drug discovery and development. 1234567890():,; High-throughput experimentation (HTE) techniques hold the potential to revolutionize modern catalysis and reaction discovery by enabling the exploration of myriad reaction conditions in a time and resource-efficient manner[1,2,3,4,5,6]. We foresee the synergistic combination of droplet microfluidics, MS, and photoredox catalysis as an enabling platform for accelerating pharmaceutical discovery and development, with a concerted emphasis on time and material efficiency
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