Partition coefficients multiprotic substances

Avdeef, A. pH-metric logP. Part 1. Difference plots for determining ion-pair octanol-water partition coefficients of multiprotic substances. Quant. Struct.-Aaiv. Relat. 1992, 11, 510-517. 

We considered micro-pA), values in Section 3.6. A parallel concept applies to partition coefficients (of multiprotic molecules) namely, if an ionizable substance of a particular stoichiometric composition can exist in different structural forms, then it is possible for each form to have a different micro-log P [224,243,273,275], When logP is determined by the potentiometric method (below), the constant determined is the macro-log P. Other log/1 methods may also determine only the macroscopic constant. 

Avdeef, A., pH-Metric logP. 2. Refinement of partition coefficients and ionization constants of multiprotic substances, J. Pharm. Sci. 82, 183-190 (1993). 

Avdeef has recently reported the refinement of partition coefficients and ionization constants of multi-protic substances based on a generalized, weighted, non-linear least-squares procedure and pH titration curve. This method allows for the determination of pKa and logP values of multiprotic substances with fairly close ionization constants. 

Ageneraiized, weighted, noniinear ieast squares procedure is deveioped, based on pH titration data, for the refinement of octanoi-water partition coefficients (iog P) and ionization constants (pKa) of multiprotic substances. Ion-pair partition reactions, self-association reactions forming oligomers, and formations of mixed-substance complexes can be treated with this procedure. The procedure allows for CO2 corrections in instances where the base titrant may have CO2 as an impurity. Optionally, the substance purity and the titrant strength may be treated as adjustable parameters. The partial differentiation in the Gauss-Newton refinement procedure is based on newly derived analytical expressions. The new procedure was experimentally demonstrated with benzoic acid, 1-benzylimidazole, (+)-propranolol, and mellitic acid (benzenehexacarboxylic acid, AH6). 

A. Avdeef, Quant. Struct.-Act. Relat., 11, 510 (1992). pH-Metric Log P. 1. Difference Plots for Determining Ion-Pair Octanol-Water Partition Coefficients of Multiprotic Substances. 

A. Avdeef,/. Pharm. Sci., 82, J (1993). pH-Metric Log P. II. Refinement of Partition Coefficients and Ionization Constants of Multiprotic Substances. 

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