Lipofiliys

Lipophilicity, in chemistry and biochemistry, is the property of a compound to dissolve in fats, oils, and nonpolar solvents relative to water. It is commonly quantified by the octanol/water partition coefficient (P) and its logarithm (logP). For ionizable compounds, the distribution coefficient (logD) at a specific pH is often used to reflect real conditions in biological systems.

Measurement methods include the shake-flask assay for logP, as well as analytical techniques such as reverse-phase high-performance liquid chromatography and various computational predictions. Lipophilicity is a key determinant of a molecule’s behavior in biological environments, particularly its ability to cross cell membranes and its distribution within an organism.

Biological relevance and applications are broad. Lipophilicity influences absorption after oral administration, tissue distribution, blood-brain barrier penetration, protein binding, metabolism, and excretion. In drug design, a balance is sought: sufficient lipophilicity to enable membrane permeation and oral bioavailability, but not so high as to cause poor aqueous solubility, nonspecific binding, or toxicity. Lipinski’s Rule of Five is a common guideline and suggests a logP around or below five as favorable for many drug-like compounds.

Examples provide context: moderately lipophilic drugs often exhibit good membrane permeability but may suffer from solubility challenges; highly lipophilic molecules can accumulate in fatty tissues and exhibit off-target effects, while very hydrophilic compounds may have limited permeability. Lipophilicity is closely related to, but distinct from, general hydrophobicity and is complemented by other properties such as solubility, ionization, and molecular size.