Organophosphate diesters interfere with hypochlorous acid-induced phospholipid reactions at the air-water interface

Organophosphate diesters (di-OPEs) and hypochlorous acid (HOCl) are two typical indoor pollutants, which have been proved to negatively impact respiratory health. However, the underlying molecular mechanism of them acting on pulmonary phospholipids remains poorly understood. In this study, using 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) as a model phospholipid, di-OPEs were found that can significantly amplify interfacial chemical damage induced by HOCl. This damage amplification effect can be observed in both alkyl- and aryl-di-OPEs, which shows concentration-dependence. This phenomenon can be attributed to two synergistic effects. Firstly, acidic phosphate group of di-OPEs lowers the system pH. This stabilizes HOCl in its undissociated neutral form, thereby preserving the highly oxidative reactivity of HOCl. Secondly, the lipophilicity of di-OPEs promotes their accumulation at the air-water interface, which elevates the H⁺ concentration in interfacial region. Such high interfacial concentration of H⁺ aggravates the hydrolysis of POPG, thereby intensifying the overall chemical damage. Overall, this study offers a molecular level insight for clarifying the health implications of indoor di-OPEs in the presence of HOCl and lays the groundwork for evidence-based risk assessment.