Professor Cooks presents Hovde Distinguished Lecture on April 6
R. Graham Cooks
Hovde Distinguished Lecture
Thursday, April 6, 2023
4:30PM (Reception at 5:30PM in Leighty Commons)
"Mass Spectrometry for Chemical Synthesis and Analysis"
Ordinary chemical reactions are accelerated by orders of magnitude in the microdroplets produced during electrospray ionization. This forms the basis for a new approach to drug discovery using MS for reaction screening, small-scale synthesis and bioassays. DESI (desorption electrospray ionization) is an ionization method that uses solvent droplets to sample and ionize compounds at atmospheric pressure. It can be used for molecular imaging or for diagnostics, including intrasurgical diagnostics. Here we apply it, using high throughput robotics, to perform reaction screening (e.g. 6,144 reaction mixtures) sampling individual reactions at rates of one per second. Accelerated reactions occur in the secondary droplets generated in DESI as they move towards the mass spectrometer so that reaction products are recorded by MS. The droplets can, alternatively, be deposited on a collector surface for smallscale (ng amounts) high-throughput synthesis. The reaction products are then used in bioassays, so that DESI-MS performs the full cycle of reaction optimization, small scale synthesis and biological testing. Examples discussed will include (i) synthesis and then bioassays after late-stage functionalization of opioid antagonists, the bioactivity of which is determined in competitive binding assays and (ii) screening of compound libraries for inhibition of activity of a sulfotransferase relevant to prostate cancer. Enzyme kinetics measured by HT-DESI MS is label-free, fast and highly accurate.