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

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Abstract
A novel series of bis(acridines) was synthesized in which the 2 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 [calf thymus] and closed circular superhelical [ColE1 plasmid] DNA) experiments indicate that a highly rigid 8.8 .ANG. separated bis(acridine) monointercalates, whereas the longer and more flexible bis(acridines) are capable of bis-intercalation. 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. [The new bis(acridines) were N-9-acridinyl-.beta.-alanylamide, N-9-(2-methoxy-6-chloroacridinyl)-.beta.-alanylamide, N,N''-bis(N-9-acridinylglycyl)hydrazine dihydrobromide, N,N''-bis(N-9-acridinyl-.beta.-alanyl)-1,2-ethylenediamine, N,N''-bis(N-9-acridinyl-.beta.-analyl)-1,3-diaminopropane and N,N''-bis[N-(9-acridinyl-.beta.-alanyl)glycyl]-1,3-diaminopropane. These substances are being investigated for their chemotherapeutic activity.].