Intervention of organophosphate esters in phospholipids hypochlorination at the air-water interface

Organophosphate esters (OPEs) are a serious and pervasive indoor environmental pollutant, and their extensive use and frequent detection in indoor environments have raised growing concerns globally about their impact on the respiratory system. Simultaneously, increasing attention has been directed toward interfacial hypochlorous acid (HOCl) chemistry, particularly in relation to indoor air quality and public health. However, the molecular mechanisms underlying HOCl-mediated oxidation of phospholipids in the presence of OPEs remain unclear. This study utilized an online air-water interface reaction monitoring technique to examine the effects of ten OPEs, including alkyl, chlorinated, and aryl OPEs, on the oxidation of a model lung phospholipid 1-Palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG) exposed to HOCl at the air-water interface. The results indicated that OPEs inhibit the oxidation of phospholipids by HOCl at the air-water interface, and this inhibitory effect is correlated with the concentration of OPEs and their water-oil partition coefficient (LogP). Mechanistic studies demonstrated that the hydrophilicity of OPEs enables their incorporation into the phospholipid monolayer, resulting in a compact arrangement of POPG. This arrangement partially shields the C=C double bonds from exposure to HOCl, thereby inhibiting the oxidation of POPG at the air-water interface. These findings elucidate the molecular mechanisms by which OPEs modulate HOCl-induced phospholipid oxidation, providing a theoretical foundation for the development of specific drugs targeting related diseases.