Revisiting\nthe Enhanced Chemical Reactivity in Water\nMicrodroplets: The Case of a Diels–Alder Reaction

Often,\nchemical reactions are markedly accelerated in microdroplets\ncompared with the corresponding bulk phase. While identifying the\nprecise causative factors remains challenging, the interfacial electric\nfield (IEF) and partial solvation are the two widely proposed factors,\naccounting for the acceleration or turning on of many reactions in\nmicrodroplets. In sharp contrast, this combined computational and\nexperimental study demonstrates that these two critical factors have\na negligible effect on promoting a model Diels–Alder (DA) reaction\nbetween cyclopentadiene and acrylonitrile in water microdroplets.\nInstead, the acceleration of the DA reaction appears to be driven\nby the effect of confinement and the concentration increase caused\nby evaporation. Quantum chemical calculations and ab initio molecular\ndynamics simulations coupled with enhanced sampling techniques predict\nthat the air–water interface exhibits a higher free-energy\nbarrier of this reaction than the bulk, while external electric fields\nmarginally reduce the barrier. Remarkably, the catalytic capability\nof the IEF at the water microdroplet surface is largely hampered by\nits fluctuating character. Mass spectrometric assessment of the microdroplet\nreaction corroborates these findings, suggesting that the DA reaction\nis not facilitated by the IEF as increasing the spray potential suppresses\nthe DA products by promoting substrate oxidation. While the DA reaction\nexhibits a surface preference in water microdroplets, the same reaction\ntends to occur mainly within the core of the acetonitrile microdroplet,\nsuggesting that the partial solvation is not necessarily a critical\nfactor for accelerating this reaction in microdroplets. Moreover,\nexperiments indicate that the rapid evaporation of microdroplets and\nsubsequent reagent enrichment within the accessible confined volume\nof microdroplets caused the observed acceleration of the DA reaction\nin water microdroplets.