Ionization processes of some harmala alkaloids
Douglas, K.T.; Sharma, R.K.; Walmsley, J.F.; Hider, R.C.
Molecular Pharmacology 23(3): 614-618
1983
ISSN/ISBN: 0026-895X PMID: 6865908 Document Number: 205662
Harmaline alkaloids are finding increasing application in pharmacological studies by virtue of their ability to compete for Na+ sites (7-11), although some members of the group also compete for acetylcholine sites and aromatic amine sites. The ionization and UV-visible spectral properties of some harmala alkaloids were investigated spectrophotometrically. Harmaline and harmine had pKa values of 9.55 .+-. 0.04 and 7.45 .+-. 0.03, respectively. The ionization of harmalol was characterized by 2 processes which could be spectrophotometrically isolated from one another, allowing pKa values of 8.62 .+-. 0.15 and 11.30 .+-. 0.23 to be determined. The lower of these was ascribed to the phenolic group and the higher to the enamino site. Support for this assignment lay in the yellow color (.lambda.max 433 nm) at intermediate pH values, which was typical of a formally neutral quinone-methide structure. For harmol, pKa values of 7.90 and 9.47, reported at 21.degree. by Perrin, were reassigned with the lower value reflecting phenolic ionization, as opposed to the original literature assignment. Partition coefficients at pH 7.4 (n-heptane/water) were determined. The comparative pharmacology of these alkaloids is discussed and related to both their pKa values and the relative stability of the neutral quinone-methide structure.