Spectrofluorimetric Study of the Effects of Cyclodextrins on the Acid–Base Equilibria of Harmine and Harmane

Abstract

β-Carboline alkaloids are important compounds because they exhibit a variety of pharmacological actions. Their acid–base behaviour can be studied by spectrofluorimetry since these molecules present a remarkable native luminescence. Acid–base equilibria depend on the environment of the molecules and inclusion into cyclodextrin (CD) cavities shifts the acid–base equilibria and alters the apparent pK _a values. The influence of CDs on the acid–base equilibria of the model β-carbolines harmine and harmane is described. β-CD and γ-CD and the modified β-CDs hydroxypropyl-β-CD (HPβ-CD), 2,6-di-O-methyl-β-CD (DMβ-CD) and 2,3,6-tri-O-methyl-β-CD (TMβ-CD) were used to form the corresponding complexes with harmine and harmane in the pH range 7.8–8.0. In these buffered solutions the complexes with the different CDs exhibit an emission band with resolved peaks at 360 and 380 nm corresponding to the neutral form of harmane and with a remarkable enhancement in the emission intensity compared with aqueous solution. In the case of the complexes with β-CD and γ-CD, both the cationic and the neutral emission bands appear. However, for γ-CD the cationic band is more intense than the neutral band, the inverse being true for β-CD. In homogeneous aqueous solution at this pH value the cationic band is the only one observed and therefore the presence of the neutral band indicates the formation of inclusion complexes. In the harmane–HPβ-CD complexes, the emission bands ascribed to the anionic form are observed after addition of NaOH. This emission is only observed in homogeneous aqueous solution in strongly alkaline media outside the normal pH range.