Lipophilicity refers to the chemical property of a molecule that describes its ability to dissolve in fats, oils, lipids, and non-polar solvents versus its ability to dissolve in water (a polar solvent). It is typically quantified by the partition coefficient (log P) or distribution coefficient (log D) between octanol and water. Log P measures the ratio of concentrations of a compound in a mixture of two immiscible solvents (octanol and water), while log D accounts for the ionization state of the compound at a given pH.
Importance in Computational Drug Discovery
- Drug Absorption and Distribution: Lipophilicity affects the ability of a drug to cross cell membranes, which is crucial for oral absorption, distribution, and penetration into the central nervous system (CNS).
- Binding Affinity: Lipophilic drugs often have higher binding affinities for their targets due to better interaction with hydrophobic pockets in proteins.
- Metabolism and Excretion: Highly lipophilic compounds are generally metabolized more slowly and may be more prone to bioaccumulation, affecting their safety and efficacy profiles.
- Solubility: Balancing lipophilicity is essential for maintaining adequate solubility, which affects drug formulation and bioavailability.
- Toxicity: Excessive lipophilicity can lead to non-specific binding to proteins and other macromolecules, increasing the potential for off-target effects and toxicity.
- Protein binding: Non-specific binding to plasma and brain proteins can lead to lower bioavailability.
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