Interactions of some novel amide-linked bis(acridines) with deoxyribonucleic acid.

A novel series of bis(acridines) has been synthesized in which the two potential intercalating chromophores are separated by symmetrical amide-linked chains varying in both length and conformational flexibility. By comparison to a monointercalating adduct, mono- vs. bis-intercalative behavior has been established for the bis(acridines). Spectrophotometric (visible, circular dichroism, and fluorescence) and viscometric (linear sonicated and closed circular superhelical DNA) experiments indicate that a highly rigid 8.8 A separated bis(acridine) monointercalates, whereas the longer and more flexible bis(acridines) are capable of bis-intercalation. In addition, spectrophotometric studies suggest a correlation between the tendency of intramolecular association and the ability to bis-intercalate. The results are in agreement with predictions based on the neighbor-exclusion principle and indicate that connecting chain rigidity is capable of playing a determining role in the mono- vs. bis-intercalation mechanism.