Generalized Analysis of Electrophilic Small Molecules

Chemical construction almost universally employs highly customized product-specific analytics. A transition toward generality will remove this critical bottleneck. Here we present how the fundamental chemical property of electrophilicity can be leveraged to generalize reaction analytics. By using a simple thiol probe we transform customized analytical schemes for electrophilic small molecules into a single generalized readout by tandem mass spectrometry. We apply this strategy to acrylamides commonly found in covalent inhibitors, and subsequently show how it can be extended to other classes of electrophilic small molecules. Application of this approach to high-throughput chemical synthesis streamlines analysis, enabling rapid readouts of chemical analogs featuring acrylamides.