Partition Coefficient Calculators

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The partition coefficient (P) is the ratio of a compound's concentration in an organic solvent (typically n-octanol) to its concentration in water at equilibrium: P = [solute]_octanol / [solute]_water. LogP = log₁₀(P) is the preferred form. LogP is the primary measure of a molecule's lipophilicity (fat-loving vs. water-loving character) and is fundamental to pharmaceutical drug design, environmental fate prediction, and toxicology. In drug discovery, Lipinski's Rule of Five specifies LogP ≤ 5 for orally bioavailable drugs. LogP predicts membrane permeability, blood-brain barrier penetration, protein binding, and metabolic stability.

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LogP Formula and Interpretation

P = [compound]_octanol / [compound]_water

LogP = log₁₀(P)

  • LogP < 0: hydrophilic (water-preferring); poor membrane permeability; rapid renal clearance
  • LogP 0–3: balanced; suitable for most drugs; good oral bioavailability
  • LogP 3–5: lipophilic; good membrane penetration but may have metabolic stability issues; blood-brain barrier penetration
  • LogP > 5: too lipophilic; poor aqueous solubility; high protein binding; reduced oral bioavailability (Lipinski limit)

Distribution Coefficient (LogD)

LogD accounts for ionization at a specific pH: LogD = LogP − log(1 + 10^(pH − pKa)) for acids; different formula for bases. LogD at pH 7.4 (physiological) is more relevant for predicting drug behavior in the body than LogP.

Lipinski's Rule of Five

Orally bioavailable drugs generally have: MW ≤ 500 Da; LogP ≤ 5; H-bond donors ≤ 5; H-bond acceptors ≤ 10. These are guidelines from analysis of existing oral drugs — not hard rules. Many approved drugs violate one rule.

Measurement Methods

Shake-flask: equilibrate compound between octanol and water phases; measure concentration in each phase by UV/HPLC. HPLC-based: retention time correlates with LogP (faster = more hydrophilic). Computational: Clogp, XLogP3, ALogP — estimated from molecular structure.

Glossary

Partition Coefficient (P)
P = [compound]_octanol/[compound]_water; measures lipophilicity; LogP = log₁₀(P); LogP > 0 = lipophilic; LogP < 0 = hydrophilic; fundamental property in drug design and toxicology.
LogD
Distribution coefficient at a specific pH accounting for ionization: LogD = LogP − log(1+10^(pH−pKa)) for acids; more relevant than LogP for predicting drug behavior at physiological pH 7.4.
Lipinski's Rule of Five
Guidelines for oral drug bioavailability: MW ≤ 500 Da; LogP ≤ 5; H-bond donors ≤ 5; H-bond acceptors ≤ 10; violations of ≥2 rules predict poor oral absorption.

Frequently Asked Questions

The partition coefficient P = [compound]_octanol / [compound]_water, measured at equilibrium between n-octanol (a model for lipid membranes) and water. LogP = log₁₀(P). It quantifies lipophilicity — how much a molecule prefers fat-like vs. water environments. High LogP (lipophilic): good membrane penetration; high protein binding; potential blood-brain barrier crossing; poor aqueous solubility. Low LogP (hydrophilic): stays in water; poor membrane penetration; rapid renal elimination. In drug design, LogP is a primary property because it predicts: oral absorption; distribution throughout body (blood-brain barrier, tissue penetration); protein binding; metabolic stability.

Lipinski's Rule of Five (1997) describes properties shared by most orally bioavailable drugs from analysis of approved pharmaceuticals: molecular weight ≤ 500 Da; calculated LogP (cLogP) ≤ 5; H-bond donors ≤ 5 (NH + OH groups); H-bond acceptors ≤ 10 (N + O atoms). LogP ≤ 5 is one of the four criteria. Drug candidates violating 2+ criteria generally have poor oral bioavailability. The rule correctly predicts oral bioavailability for ~80% of drugs. Important exceptions: natural products, antibiotics, and many targeted therapies (biologics) violate the rules. The rule is a starting point for drug design, not an absolute boundary.

LogP is the partition coefficient measured (or calculated) for the neutral, non-ionized form of a molecule — a property of the compound independent of pH. LogD (distribution coefficient) is the partition coefficient at a specific pH, accounting for the ionization state of the molecule. Ionized species are generally water-soluble and don't partition into octanol. Formula for an acid: LogD = LogP − log(1 + 10^(pH − pKa)). At pH 7.4 (physiological): if pKa = 5 (acid fully ionized at pH 7.4): LogD = LogP − log(1 + 10^(7.4−5)) = LogP − 2.4. LogD at pH 7.4 is more relevant for predicting drug behavior in blood than LogP, because most drugs are ionizable acids or bases.

The blood-brain barrier (BBB) consists of tight junctions between brain endothelial cells plus efflux transporters (P-glycoprotein, BCRP). Requirements for CNS penetration: moderate LogP (1–4): enough lipophilicity to cross the lipid bilayer but not so high that the compound is trapped in peripheral tissues or rapidly cleared. Low molecular weight (< 450 Da): larger molecules don't passively diffuse across. Limited H-bonding: H-bond donors/acceptors reduce brain penetration. Not an efflux transporter substrate: P-gp pumps many drugs back into blood. LogD at pH 7.4: 1–4 is the sweet spot. BBB penetration is predicted by CNS MPO (multi-parameter optimization) score or calculated from physicochemical descriptors.