Fragment constant approach partition coefficient

Solution of equations 5-1 and 5-2 requires site-specific values as well as chemical-specific values. Critical chemical-specific properties in the above equations are the Henry s law constant (H), the organic carbon/water partition coefficient (Koc), and the effective diffusion coefficient through soil (Deff). Henry s law constants are estimated using solubility and vapor pressure values obtained from data compilations. The Koc is estimated from the octanol-water coefficient (Kow) and is commonly estimated from the Hansch and Leo (1979) fragment constant approach (TPHCWG 1997b) ... 

Octano/—Water Partition Coefficient. The Fragment approach (234—236) has been reviewed (227) and another method similar to the UNIFAC refit for Henry s constant has been proposed. Improved accuracy for many species and the abiUty to correct for temperature effects have been claimed for the newer method. 

Lipophilicity in particular, as reflected in partition coefficients between aqueous and non-aqueous media most commonly water (or aqueous buffer) and Z-octanol,has received much attention [105,141,152,153,176,199,232,233]. Logic )W for the octanol-water system has been shown to be approximately additive and constitutive, and hence, schemes for its a priori calculation from molecular structure have been devised using either substituent tt values or substructural fragment constants [289, 299]. The approximate nature of any partition coefficient has been frequently emphasized and, indeed, some of the structural features that cause unreliability have been identified and accommodated. Other complications such as steric effects, conformational effects, and substitution at the active positions of hetero-aromatic rings have been observed but cannot as yet be accounted for completely and systematically. Theoretical statistical and topological methods to approach some of these problems have been reported [116-119,175,289,300]. The observations of linear relationships among partition coefficients between water and various organic solvents have been extended and qualified to include other dose-response relationships [120-122,160,161,299-302]. 

Principles of Use. Leo s approach (Hansch and Leo [14]) to the estimation of octanol/water partition coefficients uses empirically derived atomic or group fragment constants (f) and structural factors (F). All calculations are carried out in terms of log Kow ... 

One of the earliest applications of expert systems in the field of QSAR was the development of calculation schemes for octanol/water partition coefficients. Although the early work with n constants had shown that they were more or less additive, a number of anomalies had been identified. In addition, in order to calculate log P values from n constants it is necessary to have a measured log P for the parent and this, of course, is often unavailable. One approach to the question of how to calculate log P from chemical structure is to analyse a large number of measured log P values so as to determine the average contribution of particular chemical fragments (Nys and Rekker 1973). The fragment contributions constitute the rules of the expert system, extra rules being supplied in the form of correction factors. Operation of this expert system consists of the following few simple steps. 

---