Membranepermeant

Membrane‐permeant refers to the ability of a chemical compound or biological molecule to traverse biological membranes, such as the phospholipid bilayer of a cell. A membrane‑permeant species typically possesses physicochemical properties that facilitate its passive diffusion across the lipid bilayer, including moderate lipophilicity, a small or flexible molecular size, and the absence of charged or highly polar groups at physiological pH. Many pharmaceutical agents, signaling molecules, and metabolic substrates are designed or naturally occurring to be membrane‑permeant in order to reach intracellular targets.

Passive diffusion is the most common route for membrane‑permeant molecules, driven by a concentration gradient. The rate of diffusion correlates with the partition coefficient of the compound between an aqueous phase and a lipid phase. Molecules with high partition coefficients—for example, steroid hormones, lipophilic vitamins, and many lipophilic drugs—efficiently cross membranes. In contrast, hydrophilic or highly charged compounds typically require transporter proteins or vesicular transport mechanisms to cross membranes and are therefore considered membrane‑impermeant unless they are co‑transported with a carrier or modified chemically to increase lipophilicity.

Active transport can also contribute to membrane permeability when a compound is a substrate for specific membrane transporters, such as uptake transporters in the intestine or efflux pumps in the blood–brain barrier. These proteins can mediate the movement of otherwise polar molecules across membranes, expanding the range of compounds that can reach intracellular compartments.

Membrane permeability is a critical parameter in pharmacokinetics and drug development. It influences oral bioavailability, distribution, and the ability of a drug to enter target tissues. Structural modifications, such as esterification or the addition of lipophilic side chains, are common strategies to increase membrane permeability and enhance therapeutic efficacy.