The Interaction of Antimalarials with Nucleic Acids

Abstract

The degree of binding between antimalarials and purified yeast nucleic acid was studied spectrophotometrically. Equations for association constants for both monomeric and dimeric spp. of ligands, and for degrees of dissociation were derived and applied to the spectrophotometric data. The combination of both the acridine and quinoline derivatives with the ribonucleic acid corresponded with the monomeric rather than the dimeric spp. of ligand. The constant for binding of the acridine derivative was approx. 7.6 times that of the quinoline derivative at the same pH and ionic strength. This difference in binding power suggests that such forms as hydrogen bonds and van der Waals forces are involved in the combination in addition to coulombic forms. Increase of ionic strength from 0.1 to 1.05 by addition of either NaCl or MgSO4 produced a 19.5-fold decrease in the binding of the acridine derivative by the ribonucleate ion. Alkaline hydrolysis of the ribo nucleate with NaOH resulted in a steady decrease in binding power for acridine derivative with time, probably due to cleavage of the bridging phosphate ester linkages of the nucleic acid.