Synthetic models of deoxyribonucleic acid complexes with antimalarial compounds. 3. Forces involved in the stacking interaction between aminoquinoline and the nucleotide bases.

As an approach to the problem of the nature of the forces responsible for the stacking interactions between the aminoquinoline ring of the antimalarial chloroquine and the monomeric nucleotide bases, we have examined models in which the aromatic nucleus of the drug is linked to the nucleotide bases by a trimethylene chain. The degree of stacking of the models was determined in different conditions of solvent, pH, and temperature by hypochromism measurement in the UV. The results show that forces of the donor-acceptor type, due to the presence of a positive charge on the quinoline ring at neutral pH, do not bring an important contribution to the stacking interaction between the aminoquinoline and the nucleotide bases, while the influence of the solvent water is fundamental.