impermeants

Impermeants, in biology and pharmacology, are molecules or ions that cannot readily cross biological membranes such as the plasma membrane or the blood-brain barrier under normal conditions. They remain largely confined to the extracellular space or the outside of the cell because their physicochemical properties impede passive diffusion.

Factors that influence impermeability include polarity, charge, size, hydrogen-bonding capacity, and lipophilicity. The presence or absence of specific transport mechanisms, such as channels or carriers, also determines permeability. Small nonpolar molecules cross membranes readily; polar but uncharged molecules are slower; charged or highly polar molecules are often impermeant. The membrane potential and the composition of the lipid bilayer further influence permeability.

Common examples of impermeants are inorganic ions like sodium and chloride, and large hydrophilic macromolecules such as proteins or nucleic acids, which generally do not cross membranes without specialized transport processes. In experimental settings, impermeants are used to distinguish extracellular from intracellular compartments, to test membrane integrity (for example, propidium iodide is impermeant to live cells but enters damaged cells), and to analyze extracellular space in neuroscience and physiology. In pharmacology and drug design, impermeants can be used to limit a compound's distribution to outside cells or to restrict its action to extracellular targets; conversely, researchers develop permeant prodrugs to improve intracellular delivery.

Related concepts include permeants, which can cross membranes, and transport mechanisms such as channels and transporters that facilitate passage for otherwise impermeant molecules.