Nitrogen dioxide solubility and permeation in lipid membranes

Nitrogen dioxide (NO2) is an important oxidant molecule in biology that is produced by several biological processes, and it is also an important air pollutant. It can oxidize proteins and lipids with important consequences on their biological functions. Despite its relevance, the interaction of NO2 with the cell barrier, the lipid membrane, is poorly understood. For instance, can lipid membranes limit NO2 diffusion? To estimate the permeability of lipid membranes to NO2 it is necessary to learn more about its solubility in the lipid phase. However, experimental data on NO2 solubility is very limited. To improve our knowledge on this matter, we used a mixed approach consisting in calculating the solubility of NO2 and related diatomic and triatomic gases (NO, O2, CO2, etc.) in different solvents using quantum calculations and Tomasi’s Polarizable Continuum Model and validating and correcting these results using experimental data available for the related gases. This approach led to an estimated partition coefficient for NO2 of 2.7 between n-octanol and water, and 1.5 between lipid membranes and water, meaning that NO2 is a moderately hydrophobic molecule (less than NO, more than CO2). Based on the solubility-diffusion permeability theory, the permeability coefficient was estimated to be 5 cm s−1, up to 4000 times higher than that of peroxynitrous acid. It is concluded that lipid membranes are not significant barriers to NO2 transport.