The binding of primaquine, pentaquine, pamaquine, and plasmocid to deoxyribonucleic acid.

The binding of four 8-aminoquinoline antimalarials (primaquine, pentaquine, pamaquine, and plasmocid) to native and denatured calf thymus DNA has been studied by equilibrium dialysis and direct spectrophotometry. The binding of the 8-aminoquinolines to DNA is (a) accompanied by a decrease in absorbance of the ligand, (b) decreased by an increase in ionic strength, (c) decreased by addition of Mg2+ to a greater extent than would be expected from ionic strength effects alone, and (d) decreased under some conditions by the presence of 4 M urea. In 0.01 M potassium phosphate (pH 6), the total binding of the 8-aminoquinolines to various DNA preparations at DNA nucleotide to aminoquinoline ratios of 6 or greater occurs in the following order: native DNA = denatured DNA > native DNA in 4 M urea > denatured DNA in 4 M urea. At low ionic strengths and pH 6, the binding of the singly protonated 8-aminoquinolines is less than, but comparable to, the binding of chloroquine, a divalent cation at the same pH. At a DNA nucleotide to aminoquinoline ratio of 10 and an ionic strength of 0.012 (pH 6), the percentages of the aminoquinolines bound to native DNA decrease in the following order: chloroquine > pentaquine > plasmocid > primaquine > pamaquine. At an ionic strength of 0.15 or greater, the binding of pentaquine and plasmocid equals or exceeds the binding of chloroquine to native DNA. Evidence is presented for the occurrence of at least two spectrally distinct bound forms for each 8-aminoquinoline.