Products and mechanism of the reaction of ozone with phospholipids in unilamellar phospholipid vesicles

Chem Res Toxicol. 1992 Jan-Feb;5(1):134-41. doi: 10.1021/tx00025a023.

Abstract

While considerable effort has been expended on determining the health effects of exposure to typical urban concentrations of O3, little is known about the chemical events responsible for toxicity. Phospholipids containing unsaturated fatty acids in the cell membranes of lung cells are likely reaction sites for inhaled ozone (O3). In this study, we examined the reaction of O3 with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in unilamellar phospholipid vesicles. Reaction of ozone with the carbon-carbon double bond of POPC yielded an aldehyde and a hydroxy hydroperoxide. The hydroxy hydroperoxide eliminated H2O2 to yield a second aldehyde. Upon further ozonolysis, the aldehydes were oxidized to the corresponding carboxylic acids. A material balance showed that no other reaction consumed POPC and O3 or produced these products. As a mechanistic probe, we measured incorporation of oxygen-18 from 18O3 into aldehyde, carboxylic acid, and H2O2. Approximately 50% of the aldehyde oxygen atoms were derived from O3. Oxygen in H2O2 was derived solely from O3, where both oxygen atoms in a molecule of H2O2 were from the same molecule of O3. One of the carboxylic acid oxygen atoms was derived from the precursor aldehyde, while the other was derived from O3. These results support the following mechanism. Cleavage of the carbon-carbon double bond of POPC by O3 yields a carbonyl oxide and an aldehyde. Reaction of H2O with the carbonyl oxide yields a hydroxy hydroperoxide, preventing formation ozonide by reaction of the carbonyl oxide and aldehyde. Elimination of H2O2 from the hydroxy hydroperoxide yields a second aldehyde. Oxidation of the aldehydes by O3 yields carboxylic acids.

MeSH terms

  • Aldehydes / chemistry
  • Carboxylic Acids / chemistry
  • Chromatography, High Pressure Liquid
  • Hydrogen Peroxide / chemistry
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Membranes, Artificial
  • Ozone / chemistry*
  • Phosphatidylcholines / chemistry
  • Phospholipids / chemistry*

Substances

  • Aldehydes
  • Carboxylic Acids
  • Membranes, Artificial
  • Phosphatidylcholines
  • Phospholipids
  • Ozone
  • Hydrogen Peroxide
  • 1-palmitoyl-2-oleoylphosphatidylcholine