Analysis of the M

As pointed out by van de Waterbeemd and Testa [3] lipophilicity is mainly governed by the size (volume or surface) and the polarity of a solute:

lipophilicity = bulkiness - polarity

The same relations seem to be given for chromatographic retention mechanisms. Horvath and coworkers [38] assume that the slope of the RM/(p relation gives the hydrophobic contact surface area of a solute. It should be noted, that Horvath and coworkers [38] define the modifier fraction tp in the solvent by a volume/volume relation, while Soczewinski and Golkiewicz [46] prefer the use of the logarithm of the molar modifier fraction.

Only a small number of authors [47, 48] follow the above interpretations of Horvath; nevertheless, the results of other groups investigating the correlation of slope and RMw in ft.vAp relations are not contradictory to the theoretical considerations of Horvath. Both Biagi et al. [15] and Kuchar and Jeh'nkova [43] have shown high correlations of slope and RMv/ in the case of structurally related compounds, which differ only marginally in polarity. In the slope//?Mw correlations of Biagi et al. [15, 49] the two outliers observed among 15 p-carbolines were the two nonaromatics in the series. Dross and Sonntag [48] have shown that, in contrast to benzoic acids, their test set of non polar structures exhibited lower slopes as compared with /?Mw; in terms of Eq. (10) this is easily understandable when inserting RMvi as the lipophilicity parameter and defining the slope as an indicator of bulkiness as corresponds to Horvath.

Our group is currently exploring the possibility of deriving a polarity parameter from the above relation. Extrapolation of the linear part of the relation to waterfree conditions gives a theoretical value for an RM exclusively governed by partitioning processes. The difference between this value and the RM derived experimentally with pure modifier is similar to [5 in the case of compounds with pure hydrogen bond acceptor properties, and very similar to the product a x [5 in the case of compounds exhibiting both acceptor and donor properties.

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