Air–liquid interfaces of the water microdroplets as nanoreactors: Environmental modulation of catecholamine oxidation and oxidative damage

Catecholamines (CAs), endogenous neurotransmitters, accumulate in pulmonary fluids under pathological conditions (e.g., chronic stress and pulmonary inflammation), yet their oxidation fate within the microenvironment-a high-oxygen and air-liquid interface-remains unclear. Here, we employ a microdroplet system (a platform mirroring microenvironment interfacial properties) to investigate the interfacial oxidation of CAs, under environmentally relevant conditions. We demonstrate that •OH generated at the air-liquid interface dominates CAs-to-toxic product conversion, with reaction rates surpassing bulk-phase kinetics by over six orders of magnitude. Unlike conventional electrocatalytic methods, this process requires no catalysts, oxidants, or external energy inputs-only nebulized aqueous droplets. The mechanism, validated by MS/MS analysis, extends universally to six CAs, completing oxidation within hundreds of microseconds. Moreover, we demonstrate that environmental factors, such as pH, metal ions, and antioxidants, can significantly modulate the oxidation pathway and intermediate formation of CAs in microdroplets. This work advances the understanding of endogenous chemical toxicity in air-liquid interface microenvironments and provides a predictive framework for assessing oxidative hazards in patients with CA dysregulation under environmental stress.