Determination of ionization constants of N-imidazole derivatives, aromatase inhibitors, using capillary electrophoresis and influence of substituents on pKa shifts.
Capillary electrophoresis (CE) was used as a method to determine the acidity constants of eight aromatase inhibitors. This method was validated by comparison of results obtained with a traditional method, UV spectroscopy, and additionally with computational calculations. We confirmed here, with our series of compounds, that capillary electrophoresis is an attractive method for pKa measurements which is based on migration time or mobilities of the ionic species over a range of pH values. The precision of pKa measurements of N-imidazole derivatives is useful to observe pKa shifts induced by chemical modifications introduced on adjacent aromatic rings such as heterocycle (benzoxa- or benzothiazolinone) or substituted benzyle. The knowledge of these pKa values is a great interest to predict migration of solutes and qualitative interactions with ionized cyclodextrines as chiral selectors in further enantioseparative CE studies.
Foulon
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C
Laboratoire de Chimie Analytique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, BP 83, 3 Rue du Pr. Laguesse, 59006 Lille Cedex, France.
Danel
C
C
Vaccher
C
C
Yous
S
S
Bonte
J P
JP
Goossens
J F
JF
D047072:Aromatase Inhibitors; D002021:Buffers; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D007477:Ions; D009995:Osmosis; D015203:Reproducibility of Results
D047072:Aromatase Inhibitors; D002021:Buffers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007477:Ions