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The in vivo antitumor effectiveness [as measured by the percentage increase in life-span (ILS%)] of 28 diacridine bis-intercalators of nucleic acids shows a highly significant correlation with their effect on phenomena associated with plasma membrane as well as a high degree of structural specificity. In contrast, the ILS% does not correlate with the uptake of these diacridines by cells, nor with the inhibition of RNA synthesis or of DNA synthesis or with the inhibition of growth of cells in culture. The possibility that the antitumor effectiveness of actinomycin D, another DNA intercalator, is associated with sites of action other than the hibition of RNA synthesis is discussed.

An homologous series of diacridines containing two 9-aminoacridine chromophores linked via a simple methylene chain has been studied in order to investigate the minimum interchromophore separation required to permit bifunctional intercalation. Viscometric, sedimentation, and electric dichroism experiments show that compounds having one to four methylene groups in the linker are restricted to monofunctional intercalation, whereas the interaction becomes bifunctional when the chain length is increased to six carbons or more. The results indicate that bifunctional reaction occurs with an interchromophore distance not exceeding 8.8 A, implying that intercalation by these compounds is not subject to neighbor exclusion if the mode of binding is of the classical intercalation type.