Lipophilicity

Lipophilicity is the tendency of a substance to dissolve in lipids or other nonpolar environments rather than in water. It influences how substances partition between aqueous and nonpolar phases.

Partition coefficient: A ratio describing how a substance distributes between two immiscible phases at equilibrium. It quantifies lipophilicity by comparing a compound’s concentrations in nonpolar and aqueous phases.
Lipinski's rule of five: A heuristic identifying molecular properties associated with poor oral absorption or permeation in drug candidates. Its lipophilicity threshold helps flag compounds that may be too hydrophobic for oral drug development.
Hydrophobic effect: The tendency of nonpolar substances to aggregate in water as water molecules reorganize around them. It helps explain why nonpolar surfaces favor association with lipids rather than aqueous surroundings.
Hydrophobicity: The tendency of a substance or surface to avoid interaction with water. It is closely related to lipophilicity but describes water avoidance rather than preference for lipid-like phases.
Octanol–water partition coefficient: The equilibrium concentration ratio of a compound between octanol and water, commonly reported as log P. Octanol and water provide a standard pair of phases for measuring neutral compounds’ lipophilicity.
Blood–brain barrier: A selective interface between blood and brain tissue formed by specialized brain endothelial cells. Lipophilicity can aid passive entry, but excessive lipophilicity may hinder useful brain exposure.
Aqueous solubility: The maximum amount of a substance that dissolves in water under specified conditions. A compound can be lipophilic yet poorly soluble in water, creating a formulation challenge.
Log P: The base-ten logarithm of a neutral compound’s partition coefficient between octanol and water. This widely used numerical measure expresses lipophilicity on a logarithmic scale.
Distribution coefficient: A ratio of a compound’s total concentrations across two phases at a specified pH. It captures pH-dependent partitioning when a compound exists in multiple ionization states.
Drug absorption: The movement of a drug from its administration site into systemic circulation. Lipophilicity influences membrane permeation, while also affecting dissolution in aqueous fluids.

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