Direct comparison
LogP vs LogD: Lipophilicity Compared
LogP is a single fixed value for a compound's neutral form; LogD varies with pH. Why LogD at pH 7.4 matters most for ionizable drug candidates.
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How do LogP, LogD (pH 7.4) compare side by side?
The table below compares LogP, LogD (pH 7.4) across 10 procurement-relevant dimensions, from what it measures through correlation with passive membrane permeability.
Side-by-side comparison
| Dimension | LogP | LogD (pH 7.4) |
|---|---|---|
| What it measures | Partition coefficient of the neutral (un-ionized) species only, between n-octanol and water | Distribution coefficient across ALL ionization states (neutral + ionized) present at a specified pH |
| Ionization state | Not accounted for — assumes the compound is fully un-ionized | Explicitly accounted for, via the compound’s pKa and the surrounding pH |
| pH dependence | None — a single fixed value for a given compound at any pH | Varies with pH; must always be reported together with the pH it applies to |
| Governing relationship | LogP = log10([un-ionized solute]octanol ÷ [un-ionized solute]water) | LogD(pH) ≈ LogP − log10(1 + 10^(pH−pKa)) for an acid; LogP − log10(1 + 10^(pKa−pH)) for a base |
| Value for non-ionizable compounds | Same value as LogD at any pH | Converges exactly to LogP — no ionizable group means no pH-dependent species split |
| Value for ionizable compounds at pH 7.4 | Can overstate effective lipophilicity if the compound is substantially ionized at physiological pH | Reflects the real neutral/ionized mix present in plasma and most physiological compartments |
| Typical reporting context | Medicinal chemistry SAR tables, early hit-to-lead screening, calculated cLogP filters | ADME/PK characterization, permeability and formulation assessment, PBPK model inputs |
| Standard measurement methods | Shake-flask (at a pH where the compound is fully neutral); computational cLogP | Shake-flask or reversed-phase HPLC retention correlation at controlled pH; potentiometric titration |
| Use in early druglikeness screening | Yes — e.g. Lipinski’s Rule of Five uses calculated LogP ≤ 5 as one of four heuristics | Not typically used in Rule-of-Five-style filters, which predate widespread LogD adoption |
| Correlation with passive membrane permeability | Reliable only for compounds that stay largely neutral at the membrane | Correlates better with observed permeability/absorption for ionizable acids and bases |
Common questions
Common questions about LogP vs LogD (pH 7.4)
Is LogD always reported at pH 7.4?
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Not necessarily — pH 7.4 (blood plasma pH) is the most common default because it is the physiologically relevant condition for systemic exposure, but LogD can be measured or calculated at any pH. Formulation scientists modeling oral absorption often also need LogD at gastric pH (roughly 1–2) and intestinal pH (roughly 5–7) to capture pH-dependent behavior along the GI tract.
When is LogP alone sufficient, and LogD unnecessary?
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For a compound with no ionizable functional group across the physiologically relevant pH range (no pKa roughly between 2 and 12), LogP and LogD are mathematically identical at every pH. Reporting LogP alone for that compound is not a shortcut — it is the complete answer, since a separate LogD figure would just repeat the same number.
Can LogD ever be higher than LogP for the same compound?
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No, not for a typical acid or base. Both terms in the LogD-from-LogP correction equation are always zero or positive, so ionization only ever pulls the observed distribution ratio down from LogP, or leaves it unchanged for a fully neutral species — it never pushes LogD above LogP.
Why does a weakly basic amine often have a much lower LogD(7.4) than LogP?
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A base with a pKa well above 7.4 (e.g. around 9) is predominantly protonated — ionized and more water-soluble — at physiological pH. Its LogP describes the fully neutral form, which is not the form most of the molecule is actually in at pH 7.4, so LogD(7.4) comes in noticeably lower and is the more realistic descriptor of its behavior in plasma.
