Reactive Ions in Aqueous Electrospray Microdroplet Experiments Originate from Electrical Discharge

Electrospray-based microdroplet experiments have been widely reported to enable unusual chemical reactivity, often supported by detection of reactive radical ions proposed as evidence of droplet-specific redox chemistry. Using internally referenced accurate-mass measurements, we assign elemental compositions to low-m/z ions and show that radical cations including H₂O^+•, N₂^+•, N₃^+•, and O₂^+• form at electrospray onset using the same emitter and applied potential with or without solvent infusion across multiple ion source configurations. These results show that formation of these ions does not require microdroplets. Accurate-mass measurements further show that the widely reported m/z 36 ion corresponds to the ammoniated water cluster NH₄⁺(H₂O) rather than the water dimer radical cation (H₂O)₂^+•. The distributions of low-m/z radical ions depend strongly on background gas composition and applied voltage but remain strongly correlated between conditions with and without electrospray-generated droplets, including under conditions that also generate intact protein ions in native-like charge state distributions. These data indicate that discharge-driven gas-phase chemistry can occur concurrently with electrospray ionization across a broad range of conditions. Together, these results show that electrical discharge is a major source of small radical ions during electrospray-based microdroplet experiments and that no droplet-specific contribution is required to explain the observed low-m/z ion distributions. These findings highlight the importance of experimental controls that distinguish discharge-driven processes from droplet-phase reactivity when assigning reaction mechanisms.