DESIGN, SYNTHESIS, AND DNA-BINDING PROPERTIES OF BIFUNCTIONAL INTERCALATORS - COMPARISON OF POLYMETHYLENE AND DIPHENYL ETHER CHAINS CONNECTING PHENANTHRIDINE

A bifunctional DNA intercalating agent N,N''-(4,4''-oxydibenzyl)bis(phenanthridinium chloride) (9) was synthesized. Interaction of this compound with DNA was compared to an analogous bifunctional intercalator, N,N''-decamethylenebis(phenanthridinium bromide) (10) and to analogous monofunctional intercalators. Viscometric titrations with sonicated calf thymus DNA show compound 9 to be a bifunctional intercalator. Thermal denaturation of calf thymus DNA and Scatchard analysis of the DNA binding of these mono- and bifunctional intercalators show that the relatively rigid compound 9 has a significantly higher affinity for DNA. X-ray crystallographic studies of 9 indicate that the phenanthridine rings are parallel and properly spaced for bifunctional intercalation. This conformation is consistent with a neighbor exclusion model. Crystallographic studies of 10 indicate that the phenanthridine rings are coplanar in contrast to the solution DNA binding properties. [DNA intercalating agents are of interest as antitumor and chemotherapeutic agents.].