The determination of dissociation constants and partition coefficients of phenothiazine derivatives

Vezin, W R; Florence, Alexander T.

doi:10.1016/0378-5173(79)90006-1

Cited by 8 publications

(1 citation statement)

References 10 publications

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“…To obtain more insight into this problem one needs to ctudy the influence of ionization on the lipophilicity in more detail by exploring the effect of pH on the distribution process. In the relevant literature there are a number of studies (Ezumi and Kubota, 1980;Moser et al, 1975;Murthy and Zografi, 1970;Le Petit, 1977, 1980Schaper, 1979, Tsuji et al, 1977Unger and Feuerman, 1979;Vezin and Florence, 1979;Wang and Lien, 1980;Yalkowsky and Morozowick, 1980) dealing with the pH-dependent partitioning of protolytes, some of which are more detailed than others. In this literature one frequently encounters the asstimption that the charged species of a molecule are not found in the organic phase.…”

Section: Introductionmentioning

confidence: 99%

Influence of ionization and ion-pair formation on lipophilicity of some 4-hydroxycoumarin derivatives in the octanol-water system

Giesen

Janssen

1982

International Journal of Pharmaceutics

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SummaryThe pH-dependent distribution of weak acids in the octanol-water system was investigated. For a series of six 4-hydroxycoumarins, substituted at position 3, the apparent partition coefficient or the distribution coefficient, Per,,,, was measured in the pH range 1-i 1. The log Parr, -pH profiles obtained are in complete agreement with the theory. At high pH the value of Pap,, is independent of pH, but dependent on the concentration of counterions (Na+ in this study) in the aqueous phase; in other words ion-pair extraction occurs. The pNa (-log [Na+ ])-dependent distribution is analogous to the pH-dependent distribution, except in the case of 4-hydroxycoumarin. Evidence was found. that the sodium ion-pair of 4-hydroxycoumarin dissociates considerably in the octanol phase. A large discrepancy was noted between the experimentally obtained log P values and the theoretical values calculated using the hydrophobic fragmental constant system. Log Parr, values obtained under conditions where the compounds are ionized in the aqueous phase depend on both the partition coefficient and the dissociation constant of the acid or salt. Partition coefficients of the sodium ion-pairs obtained by extrapolation are just slightly lower than the partition coefficients of the undissociated acids.

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Section: Introductionmentioning

confidence: 99%

Influence of ionization and ion-pair formation on lipophilicity of some 4-hydroxycoumarin derivatives in the octanol-water system

Giesen

Janssen

1982

International Journal of Pharmaceutics

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A technique for the comparison of biological distribution and solvent partition of drugs

1983

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ClogPalk: a method for predicting alkane/water partition coefficient

Kenny

Montanari

Prokopczyk

2013

J Comput Aided Mol Des

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Alkane/water partition coefficients (P(alk)) are less familiar to the molecular design community than their 1-octanol/water equivalents and access to both data and prediction tools is much more limited. A method for predicting alkane/water partition coefficient from molecular structure is introduced. The basis for the ClogP(alk) model is the strong (R² = 0.987) relationship between alkane/water partition coefficient and molecular surface area (MSA) that was observed for saturated hydrocarbons. The model treats a molecule as a perturbation of a saturated hydrocarbon molecule with the same MSA and uses increments defined for functional groups to quantify the extent to which logP(alk) is perturbed by the introduction each functional group. Interactions between functional groups, such as intramolecular hydrogen bonds are also parameterized within a perturbation framework. The functional groups and interactions between them are specified substructurally in a transparent and reproducible manner using SMARTS notation. The ClogP(alk) model was parameterized using data measured for structurally prototypical compounds that dominate the literature on alkane/water partition coefficients and then validated using an external test set of 100 alkane/water logP measurements, the majority of which were for drugs.

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The determination of dissociation constants and partition coefficients of phenothiazine derivatives

Cited by 8 publications

References 10 publications

Influence of ionization and ion-pair formation on lipophilicity of some 4-hydroxycoumarin derivatives in the octanol-water system

Influence of ionization and ion-pair formation on lipophilicity of some 4-hydroxycoumarin derivatives in the octanol-water system

A technique for the comparison of biological distribution and solvent partition of drugs

ClogPalk: a method for predicting alkane/water partition coefficient

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