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The linearity of the log k' versus ô plots were checked at the proper concentration range. The slope S and the intercept log k’w values were used for the calculation of ô0 values when the correlation coefficient of the fit was higher than 0.998. The published slope and intercept values were used for the calculation of the chromatographic hydrophobicity index, when the authors revealed acceptable high correlation coefficients for the linear fit. The log P values of 500 compounds were calculated by ProLogP Version 4.1 software package (CompuDrug Chemistry Ltd., Budapest, Hungary). The correlation analysis was carried out by the Drugidea program system developed for drug design (Chemicro Ltd., Budapest, Hungary).
Table 1 in the Appendix contains the calculated chromatographic hydrophobicity indices (Ôî,àñ¹ Ôî.ìåîí) and the calculated log P values of 22 nicotinate esters. The calculated log P and ô0 values referring to methanol for 35 monohydroxyl aromatics are presented in Table 2. The log P and ô0 values of 30 pesticides and 45 phenoxycarbonic acid derivatives are summarized in Table 3 and 4. The calculated log P and ô0,ìåîí values of the 113 aromatic hydrocarbons are shown in Table 5. The obtained ô0 and log P data of 143 acidic, basic, and neutral drugs can be seen in Table 6. The ô0 AcN and the ô0,Ìåîí data and log P values of 16 drug molecules are presented in Table 7. Table 8 contains the calculated data of morphine and tricyclic derivatives obtained from their ion-pair chromatographic retention data.
The calculated hydrophobicity index data of the benzodiazepine, deoxyuridine, and aniline derivatives are shown in Tables 9-11, respectively. Tables 12-14 show the chromatographic
hydrophobicity index values for adenosine monophosphate, barbiturate, and /Ç-lactam antibi-otic derivatives, respectively.
The correlation between ôÎ ÌåÎÍ and <fr0 AcN values for the compounds in Table 1, 4, and
7 was also investigated. These two values refer to isoelutropic eluant mixtures, as they both mean mobile-phase composition by which the same retention (log k' = 0) can be obtained. Significant correlation between the two types of chromatographic hydrophobicity indices was found for 72 compounds as described by Eq. (21).
Ôî.ìåîí = 0.82 $0 AcN + 20.46 (21)
n = 72 r = 0.96 s = 5.0
where n stands for the number of compounds, r is the correlation coefficient, s shows the standard error of the estimate. Equation (21) suggests a calculation method for converting the hydrophobicity indices from acetonitrile to methanol. The standard error of the estimate shows that, in spite of the fact that the data of the 72 compounds were obtained by different columns and buffers or neat water, the hydrophobicity index values obtained with acetonitrile can be calculated to methanol with ±5% error.
The correlation of ô0 Acn hydrophobicity index values with the calculated log P values for the data of 140 compounds can be described by Eq. 22:
<I>o,acn = 9.31 log P + 37.94 (22)
n = 140 r = 0.88 5 = 12.8
Equation (22) shows the significant correlation between the two parameters, although because the relatively low correlation coefficient r and the high standard error of the estimate s, it cannot be used for the measurements of the log P values. The plot of the ô0 Acn values against the log P values can be seen in Fig. 6. Similarly, statistically significant correlation could be found between the ôï M„oH and the log P values for the data of 448 compounds:
Ôî.ìåîí = 7.08 • log P + 42___________________________________________________________________(23)
n = 448 r = 0.787 5 = 13.48
On the basis of Eq. (23) the exact measurements of log P cannot be carried out by the measurements of the chromatographic hydrophobicity index, but the good correlation shows that, even for a large set of compounds, the relation exists. The high standard error of the
Figure 6 The plot of log P values and ô0 AcN values for 140 compounds listed in the Appendix [Tables 1, 4, 7-10, and 15] [Eq. (22)]. (From Ref. 43.)
estimate (± 13%) can be due to error in the calculation of partition coefficients, to error in the measurements of ô0 values, and also to error caused by differences in the applied chromatographic conditions. The main reason, however, for the lack of high correlation coefficients (higher than 0.99) is that we cannot expect to properly model from the reversed-phase chro-matographic partition coefficients another partition system, such as 1 -octanol-water, for structurally unrelated compounds.
The advantages of using ô0 values as a measure of hydrophobicity of the compounds are that they are valid for structurally related and unrelated compounds, they have a physical meaning (i.e., a certain eluant composition by which a certain retention can be achieved) so it can also be used for HPLC method development, and these values are relatively independent from the reversed-phase columns obtained from different manufacturers. The hydrophobicity index value ranges from 0 to 100, and the higher the value is the more hydrophobic the compound is.