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

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Abstract
The transport of gaseous compounds across biological membranes (see picture) is essential in all forms of life. In this Minireview, the authors discuss recently reported violations of the well‐established Meyer–Overton rule for small molecules, including carboxylic acids and gases, and show that Meyer and Overton continue to rule. The transport of gaseous compounds across biological membranes is 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 challenged 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–Overton rule), which predicts membrane permeabilities from the molecule′s oil–water partition coefficient. Herein, we discuss recently reported violations of the Meyer–Overton rule for small molecules, including carboxylic acids and gases, and show that Meyer and Overton continue to rule.