Mechanisms of ionization and of chemical reactions in charged microdroplets

Over the past decade the use of electrospray ionization mass spectrometry (ESI-MS) has been extended from the domain of chemical analysis to that of chemical synthesis. This development was spurred by the observation of reaction acceleration (by as much as 10⁶ times compared to analogous bulk reactions) occurring in microdroplets, entities once thought merely to deliver ionized compounds to the mass analyzer. Interest in microdroplet synthesis is fueled by the fact that many reactions proceed rapidly without catalysts or pH adjustment. In this Perspective, we explore the basis for these features and propose that field ionization (FI) followed by chemical ionization (CI) occurs in water-containing microdroplets and generates reactive intermediates that account for their unique chemistry. The implications of this proposal extend to the mechanism of ESI itself and to applications of accelerated reactions in drug discovery, green synthesis, and prebiotic chemistry.