COMPARISON OF THE BIS-INTERCALATING COMPLEXES FORMED BETWEEN EITHER DITERCALINIUM OR A FLEXIBLE ANALOG AND D(CPGPCPG)2 OR D(TPTPCPGPCPGPAPA)2 MINIHELICES - H-1-NMR AND P-31-NMR ANALYSES

The 400-MHz H-1- and 162-MHz P-31-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 P-31 {H-1} heteronuclear correlated spectroscopy and P-31-P-31 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.