(507c) Ultrahigh-Throughput Screening of Chemical Synthetic Pathways Using Desorption Electrospray Ionization Mass Spectrometry

Authors: 
Szilagyi, B., Purdue University
Koswara, A., Purdue University
Nagy, Z. K., Purdue University
Loren, B. P., Purdue University
Wleklinski, M., Purdue University
Thompson, D. H., Purdue University
Cooks, R. G., Purdue University
Jaman, Z., Purdue University
Hilger, R. T., Purdue University
Ferreira, C. E., Purdue University
Avramova, L. V., Purdue University
Sobreira, T. J., Purdue University
Falcone, C. E., Purdue University
Ewan, H. S., Purdue University
We describe a state-of-the-art automated platform for ultrahigh-throughput screening of chemical reactions based on reaction acceleration in charged microdroplets and utilizing Desorption Electrospray Ionization Mass Spectrometry (DESI-MS). The goal is to deliver an extremely rapid yet insightful qualitative yes/no analysis for the discovery of new chemistry in the order of up to 10,000 reactions per hour. The positive results are then used to guide synthesis in a more scalable setting, including in batch and flow. Using this system, particular chemical routes are prepared in parallel using reagents which are robotically pipetted and mixed in chemically-inert well plate. The routes are tested by stamping the reaction mixtures onto an inert reaction substrate, e.g. PTFE membrane, followed by electrospraying of various solvents at an angle relative to the substrate to generate secondary ionized reaction microdroplets. These microdroplets are propelled into the mass spectrometer for mass analysis. The results are then analyzed using an automated MS data analysis system developed in-house, which provides chemical reaction monitoring and intelligence for optimization of future reaction screening conditions to increase the probability of pathway discovery.