Use of reversed-phase liquid chromatography for determining the lipophilicity of α-aryl- N-cyclopropylnitrones

• Published in: Journal of pharmaceutical and biomedical analysis 2005-10, Vol.39 (5), p.1057-1062
• Main Authors: Balogh, György T., Szántó, Zoltán, Forrai, Erika, Győrffy, Werner, Lopata, Antal
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Calculated log P; Chemical Phenomena; Chemistry, Physical; Chromatography, High Pressure Liquid; CoMSIA; Cyclopropylnitrones; Fundamental and applied biological sciences. Psychology; General pharmacology; HPLC; Lipids - chemistry; Lipophilicity; Medical sciences; Methanol; Nitrogen Oxides - chemistry; Pharmacology. Drug treatments; Solvents; Water
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2005.05.019

The relationship between a reversed-phase high-performance liquid chromatography (RP-HPLC) retention parameter and various calculated log P-values of our previously synthesized α-aryl- N-cyclopropyl-nitrone derivatives was investigated. The RP-HPLC experiments were carried out with acetonitrile–water and methanol–water mixtures as mobile phases and with two kinds of stationary phases of different polarity. The retention parameter, log k w was obtained by linear extrapolation of the log k retention to pure water as the mobile phase. The calculated log P-values were C log P, ACD/log P, R log P, A log P, LogKow, X log P and M log P. Statistically, highly significant correlations were found between log k w and the calculated log P-values with squared correlation coefficients ranging from 0.771 (with A log P) to 0.956 (with C log P). In addition, the comparative molecular similarity indices analysis (CoMSIA) method was also applied to correlate the log k w retention parameter of the compounds with their molecular fields. Statistically significant CoMSIA models were obtained between log k w and the hydrophobic and steric molecular fields of our compounds. The CoMSIA models describe how the structure of the nitrone derivatives influences (through hydrophobic and steric interactions with the stationary phase) the chromatographic retention of the compounds.