Putting Enhanced Chemical Reactivity in Water Microdroplets Under the Microscope: The Case of a Diels-Alder Reaction

Often, chemical reactions are markedly accelerated in microdroplets compared to the corresponding bulk-phase. While identifying the precise causative factors remains challenging, the interfacial electric field (IEF) and partial solvation are the two widely proposed factors, accounting for the acceleration or turning on many reactions in microdroplets. In sharp contrast, this combined computational and experimental study demonstrates that these two critical factors have negligible effect on promoting a model Diels-Alder (DA) reaction between cyclopentadiene and acrylonitrile in water microdroplets. Instead, the acceleration of the DA reaction is driven by the effect of confinement. Quantum chemical calculations and ab initio molecular dynamics simulations coupled with enhanced sampling techniques predict that the air-water interface exhibits a higher free-energy barrier of this reaction than the bulk, while external electric fields marginally reduce the barrier. Remarkably, the catalytic capability of the IEF at the water microdroplet surface is largely hampered by its fluctuating character. Mass spectrometric assessment of the microdroplet reaction corroborate these findings, showing that the DA reaction is not facilitated by the IEF as increasing the spray potential suppresses the DA products by promoting substrate oxidation. While the DA reaction exhibits a surface preference in water microdroplets, the same reaction tends to occur mainly within the core of the acetonitrile microdroplet, suggesting the partial solvation is not necessarily a critical factor for accelerating this reaction in microdroplets. Moreover, experiments indicate that the rapid evaporation of microdroplets and the subsequent reagent enrichment (confinement) caused the observed acceleration of the DA reaction in water microdroplets.