UV-Visible and Carbon NMR Studies of Chloroquine Binding to Urohemin I Chloride and Uroporphyrin I in Aqueous Solutions

Article abstract of DOI:10.1021/ja00221a045

Interactions of the antimalaria drug chloroquine with urohemin I and uroporphyrin I have been studied in aqueous solutions at pH 6.0 and 22 +/- 1 deg C with UV-visible and natural abundance carbon NMR spectroscopies.Both tetrapyrroles are water soluble and were chosen because their aggregation properties are understood and can be regulated by concentration and ionic strength.Chloroquine binding to urohemin I monomer has a stoichiometry of two urohemin molecules to one chloroquine molecule with an apparent association equilibrium constant of (7.8 +/- 0.4) * 10⁸ M^-2 at pH 6.0 and a urohemin concentration of 10^-6 M.This stoichiometry is identical with that recently reported for complexes of urohemin I with another antimalarial, quinine.In that case, the binding was found to be cooperative, whereas in this case drug binding is noncooperative.Uroporphyrin binds to chloroquine with 1:1 stoichiometry and an apparent equilibrium constant of (2.8 +/- 0.2) * 10⁶ M^-1 at a uroporphyrin concentration 10^-6 M.Carbon NMR spectroscopy and optical methods best describe these complexes as cofacial ? - ? dimers with structures different from the quinine complexes of the same tetrapyrroles.