RMw and Extrapolation Methods

Since the introduction of RMm i e., the RM extrapolated to modifier-free conditions, by Biagi et al. [12], this approach has attracted steadily increasing acceptance. Nevertheless in some papers [32, 41. 42] RM values, estimated at a given modifier concentration, are still used for correlations with log Poa; Kuchar and Jelinkova [43] even state that RM and /?Mw values are mutually interchangeable as lipophilicity descriptors.

The main reason for preferring /?Mw values can be derived from Fig. 2. Plots of RM versus mobile phase content (qp) can vary considerably in slope for various test compounds. Thus, an appropriate expression of lipophilicity differences is only given at 100 % water, i.e., the extrapolated value, which better approximates the experimental conditions of lipid-phase/water partitioning systems. Another drawback of RM values -in particular those estimated at rather low water contents in the mobile phase - is that they may be partially affected by polar adsorption and not exclusively by partitioning. Finally, using /?Mw values is accompanied by extended scales allowing better resolution in characterization of lipophilicity.

Most common linear extrapolation procedures are based on trial-and-error principles. As alternative approaches, some nonlinear methods based on equations,

Figure 2. RM values of some test compounds [24] as a function of the modifier fraction in the binary solvent. Extrapolation lines for five pairs of compounds are shown exhibiting identical or very similar RMw but significantly different slopes of the extrapolation lines. In general, deviations from linearity are found at low methanol content for those compounds with steeper extrapolation lines.

methanol fraction methanol fraction

Figure 2. RM values of some test compounds [24] as a function of the modifier fraction in the binary solvent. Extrapolation lines for five pairs of compounds are shown exhibiting identical or very similar RMw but significantly different slopes of the extrapolation lines. In general, deviations from linearity are found at low methanol content for those compounds with steeper extrapolation lines.

describing the entire dependence of RM on modifier content including solvophobic and silanophilic interactions, may be useful [24, 44].

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