Topologically constrained DNA intercalators: Synthesis and DNA binding studies

The synthesis and DNA binding properties of three macrocyclic diacridines (31, 32 and 33) is discussed. The two acridines are connected by linker chains at the 4- and 9-positions. Macrocycles 31 and 32 are linked via spermine at the 9-position and have been shown to bind to DNA by bisintercalation using absorption spectroscopy titrations, thermal denaturation studies, and viscometric titrations of both calf thymus DNA and closed circular supercoiled DNA. Macrocycle 31 dissociates 10 to 40 times slower from poly(d(A-T)) ;Macrocycle 33 has a diamide linker chain at the 9-position of the acridine rings. This molecule binds to DNA by intercalation as evident from its ability to remove and reverse the supercoils in closed circular DNA. However, the results are inconclusive as to whether it binds by mono- or bisintercalation. The mono-linked diacridine 34 has been shown to bind to DNA by bisintercalation.;The preliminary synthetic results for a novel trisintercalator are discussed. Trimer 35 consists of a naphthalene diimide as the central chromophore and two 9-aminoacridines as the terminal chromophores. Trimer 35 was synthesized from 1,4,5,8-naphthalene dianhydride which was reacted with the mono-Boc protected diamine to give the N,N...