Octanoi-water partition Coefficient

Lipid soiubiiity is expressed as the octanoi water partition coefficient, its polarity it crosses the blood-brain barrier and undoubtly contributes to the analgesic effect. 

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). 

FIGURE 1 Plot of thetoxicities of para-substituted nitrobenzenes (pTm,jQ2) of the general formula N02-CgH4-X versus their octanoi/water partition coefficients (log P) data from TABLE 1. 

The relation between aqueous solubility and octanoi/water partition coefficient has been studied extensively. Mackay et al. (1980) and Banerjee et al. (1980) found their product Q to be relatively constant. However, recently. Miller et al. (1985) have analysed more accurate data for larger molecules (Miller et al. 1984) and shown that Q varies with molar volume or chlorine number in a homologous series. 

Octanoi-air partition coefficient calculated from KowI aw> where Kow is the octanol-water partition coefficient and Taw is the air-water partition coefficient or unitless Henry s law constant (Kaw = HLC/RT, where HLC = Henry s law constant, R = gas constant 8.319 Pa m /mol and r = 293 K)... 

These equations make explicit the individual polar terms that are negatively related to lipophilicity and account for most polar interactions between a solute and the two solvent phases. In the case of the octanoi/water system (Eq. [6]), the main contributor to a solute s polarity is thus its H-bond acceptor basicity 0), and to a lesser extent its dipolarity/ polarizability (ir ). In contrast, the polar interactions expressed in alkane/ water partition coefficients (Eq. [7]) are the H-bond donor acidity (a) and the H-bond acceptor basicity 0), and again to a lesser extent the dipolarity/polarizability (ir ). 

Partition coefficients Log octanoi/water Log Koc 3.52 2.44 Howard 1990 Chiou et al. 1983... 

The parameter A, being a global measure of a solute s polarity, should by definition contain the same information as Eq. [2] or [3] except for the volume term. This has been confirmed for octanoi/water (Eq. [6]) and alkane/water (Eq. [7]) partition coefficients ... 

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