Partition behavior of anilines in bulk-phase and high-performance liquid chromatographic systems: influence on correlation with biological constants.
The partition behavior of a mixed series of ring-substituted anilines in reversed-phase high-performance liquid chromatographic systems is substantially different from that observed in a classical bulk-phase partition system with n-heptane as the aprotic reference solvent. On the basis of the equivalence of each ring substituent in the p-straight-chain methylene groups (v value) as a function of the fraction of organic solvent (acetonitrile or methanol) in the mobile phase, the biased partition behavior for imperfect homologues and heterologues is verified relative to that of perfect homologues. This behavior was tentatively attributed, mainly, to differences in the hydrogen bonding capacity of the compounds, which is associated with the electronic character of the working solvent. These differences cannot be normalized through the use of extrapolated initial partition coefficient (K'o) values because of carryover effects of the solvent. When the chromatographic partition constants (K') and K'o are used, correlations with previously determined intestinal absorption rate constants are definitely worse than the correlations with the reference n-heptane partition coefficients. Possible implications of these observations on lipophilicity-biological activity correlations are briefly discussed.
Sánchez-Moyano
E
E
Department of Pharmacology and Pharmaceutics, Faculty of Pharmacy, University of Valencia, Spain.
Seco
C
C
Santolaria
A
A
Fabra-Campos
S
S
Herráez
M
M
Martín-Villodre
A
A
D000097:Acetonitriles / Q000737:chemistry; D000814:Aniline Compounds / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D000432:Methanol / Q000737:chemistry
D000097:Acetonitriles; D000814:Aniline Compounds; C023650:aniline; D000432:Methanol; C032159:acetonitrile