Self-assembly of quaternary benzo[c]phenanthridine plant alkaloids into dimer in aqueous solution

Abstract

Self-association of three biologically active natural quaternary benzo[c]phenanthridine alkaloids, nitidine, sanguinarine, and chelerythrine was studied by spectrophotometry, fluorescence spectroscopy, fluorescence decay measurements and isothermal titration calorimetry in aqueous solution. The increase of alkaloid concentration brought about moderate changes in the absorption spectra, while the fluorescence properties altered only in the case of nitidine. Enthalpy-controlled self-binding occurred and the variation of the association enthalpy was substantially compensated by the unfavorable entropic term. Nitidine dimerization was the most exothermic and the equilibrium constant of this process exceeded by a factor of ~5 the corresponding values of the other two alkaloids. The results of quantum chemical calculations agree well with the experimental data and provide information on the structural features of the dimers.