Comparison of the bis‐intercalating complexes formed between either ditercalinium or a flexible analogue and d(CpGpCpG)2 or d(TpTpCpGpCpGpApA)2 minihelices: 1H‐ and 31P‐nmr analyses

The 400‐MHz 1H‐ and 162‐MHz 31F‐nmr have been used to study complexes constituted by (a) the d(TpTpCpGpCpGpApA)2 or the d(CpGpCpG)2 self‐complementary oligonucleotides and (b) two bifunctional 7H‐pyrido [4, 3‐c] carbazole dimer drugs, the antitumoral ditercalinium (NSC 366241), a dimer with a rigid bis‐piperidine linking chain and its pharmacologically inactive analogue, a dimer with a flexible spermine‐like linking chain. Nearly all proton and phosphorus signals have been assigned by two‐dimensional (2D) nmr (correlated spectroscopy, homonuclear Hartmann‐Hahn, nuclear Overhauser enhancement spectroscopy, 2D 31P {1H} heteronuclear correlated spectroscopy and 31P‐31P chemical exchange experiments). Both drugs bis‐intercalate into the two CpG sites. The complexes show small differences in the position of the 7H‐pyrido[4, 3‐c]carbazole ring into the intercalation site and possibly in the ribose‐phosphate backbone deformation. However, the inactive analogue exhibits a longer residence lifetime in octanucleotide than the ditercalinium does. All these results are discussed in terms of differences in dimer activities.