Visible Absorption and Proton Nuclear Magnetic Resonance Studies on the Self-Association of Doxorubicin in Aqueous Solution

Abstract

The viscosity of the aqueous solution of doxorubicin increased with the addition of NaCl. Methyl p-hydroxybenzoate had a reducing effect on the viscosity of the solution enhanced by the addition of NaCl.The interaction of doxorubicin with NaCl and methyl p-hydroxybenzoate in an aqueous solution was examined by the methods of absorption spectra and proton nuclear magnetic resonance (¹H-NMR).Doxorubicin formed stacked aggregates in concentrated aqueous solutions. The increased ionic strength facilitated the self-association of doxorubicin. The addition of methyl p-hydroxybenzoate prevented the self-association of doxorubicin. It is thought that methyl p-hydroxybenzoate may interfere with the π-π stacking of doxorubicin molecules in competition with doxorubion.On the basis of the results, it is considered that the increase in the viscosity of the aqueous solution of doxorubicin is caused by the self-association of doxorubicin, and methyl p-hydroxybenzoate exerts the viscosity reducing effect by the inhibition of the self-association of doxorubicin.