The structures and stabilities of biologically active 1-phenacyl- and 1-benzoylethyl-derivatives of the pyridinium cation

• Published in: Journal of molecular structure 2012-07, Vol.1019, p.196-205
• Main Authors: Foretić, Blaženka, Picek, Igor, Damjanović, Vladimir, Cvijanović, Danijela, Milić, Dalibor
• Format: Article
• Language: English
• Subjects: 1-Benzoylethylpyridinium ion; 1-Phenacylpyridinium ion; absorption; Chlorides; Electronics; extracellular fluids; Instability; Ionization; Ionization constants; ions; iron; Ketones; Molecular structure; nuclear magnetic resonance spectroscopy; Phenyls; Spectroscopy; Stability; X-ray diffraction
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2012.03.060

► Structure–ionization relationship for carbonyl derivatives of pyridinium ion. ► Base-catalyzed decomposition of 1-phenacylpyridinium ions. ► Hydration effect on 1-benzoylethylpyridinium ions. ► Intramolecular base-catalyzed breakdown of 1-benzoylethylpyridinium-4-aldoxime ion. Chlorides of 1-phenacylpyridinium (1), 2-methyl-1-phenacylpyridinium (2), 1-benzoylethylpyridinium (3) and 1-benzoylethylpyridinium-4-aldoxime (4) were synthesized and characterized by X-ray diffraction and by electronic absorption and NMR spectroscopies. Although declared as pharmacologically active in extracellular fluids, their stability and ionization ability as well as predominant ionic forms in aqueous environments were not clarified. Comparative electronic absorption spectral studies in aqueous media at 25°C and I=0.1M performed in this work revealed the predominance of their keto-tautomeric forms and pronounced differences in stability and ionization ability. The ionization of 1-phenacylpyridinium ions 1 and 2 with pKa values of 11.57±0.04 and 11.66±0.05, respectively produced enolates (i.e., ylides), while the subsequent base-catalyzed first-order decomposition occurred via hydrate zwitterion and produced the benzoate ion and the corresponding 1-methylpyridinium derivative. A different proximate cause of the ascertained instabilities of the 1-benzoylethylpyridinium compounds (3 and 4) was determined. The base-catalyzed establishment of the ketone to gem-diol equilibrium of 3 was found to have a hydration constant smaller than 0.01. Compound 4 underwent a base-catalyzed breakdown due to the instability of its enolate form which resulted in the formation of a pyridine-4-aldoxime and phenyl vinyl ketone. Ionization constants of 3 and 4 keto-forms were estimated as the lowest possible pKa values of 12, while the pKa value of pyridinium aldoxime group of 4 was found to be 8.51±0.04. The identified stabilities and ionization abilities of these compounds were additionally supported by their presented coordination ability toward the iron(II) in the pentacyanoferrate(II) moiety.