A remote atmospheric pressure plasma source with He/O2 gas mixture, a so-called COST-Jet, is used for the treatment of aqueous phenol solutions. Phenol consumption and the formation of phenol oxidation products (catechol, hydroquinone, resorcinol, and pyrogallol) are measured with high-performance liquid chromatography/UV-VIS and direct-infusion high-resolution mass spectrometry. The variation of O2 admixture and phenol concentrations in combination with 2D axisymmetric modeling of species transport and reaction kinetics both in the gas and liquid phase allow us to obtain more information about atomic oxygen reactions at and transport across the liquid surface. The results show that most of the atomic oxygen reactions with phenol take place at the liquid surface, mainly due to the low value of Henry’s law solubility constant of atomic oxygen and the surfactant character of phenol molecules. This study indicates that other atomic oxygen reactions, e.g., the reaction with Cl anions in phosphate-buffered saline or in saline solution to form ClO, also take place predominantly at the surface of the liquid. The knowledge provided by this work has important implications for further development of plasma–liquid treatments involving atomic oxygen as a reactant.

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