Production of the Criegee ozonide during the ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes

Abstract

It is likely that Criegee ozonides are formed in small amounts in the lungs of animals breathing ozone-containing air. This makes these compounds potential candidates to act as secondary toxins which relay the toxic effects of ozone deeper into lung tissue than ozone itself could penetrate. Therefore, we have determined the yields of Criegee ozonides from unsaturated lipids in liposomal systems as a model of the types of yields of Criegee ozonides that might be expected both in the lung lining fluid layer and in biological membranes. Ozonation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes produced both cis- and trans-Criegee ozonides. These ozonides have been isolated by solid phase extraction and high-performance liquid chromatography of the ozonized lipid, and the products have been identified by two-dimensional 1H nuclear magnetic resonance. The combined yield of the cis- and trans-Criegee ozonides is 10.7 +/- 2.8% (avg. +/- SD, n = 7) with small unilamellar liposomes and 10.6 +/- 2.7% (n = 3) with large multilamellar liposomes. We had previously reported (Chem. Res. Toxicol. 5, 505-511, 1992) that ozonation of methyl oleate in sodium dodecylsulfate micelles also produces an 11% yield of the Criegee ozonides. Thus, ozonation in a variety of models gives about 11% of the Criegee ozonide, suggesting that these products also would be formed in small but significant amounts in the lungs of animals breathing polluted air. Further research on the pharmacokinetics and possible toxicity of the Criegee ozonides of fatty acids is suggested.