110 Years of the Meyer-Overton Rule: Predicting Membrane Permeability of Gases and Other Small Compounds

The transport of gaseous compounds across biological membranes essential in all forms of life. Although it was generally accepted that gases freely penetrate the lipid matrix of biological membranes a number of studies challlenged this doctrine as they found biological membranes to have extremely low-gas-permeability values. These observations led to the identification of several membrane-embedded gas channels which facilitate the transport of biological active gases, such as carbon dioxide nitric oxide, and ammonia. However, some of these findings are in contrast to the well-established solubility-diffusion model (also known as the Meyer-Overtone rule), which predicts membrane permeabilities from the molecule's oil-water partition coefficient. Herein we discuss recently reported violations of the Meyer-Overtone rule for small molecules including carboxylic acids and gases, and show that Meyer and Overtone continue to rule.