| Abstract
| - The interaction of the linear dibenzo[b,g]quinolizinium (5a) and the angular dibenzo[a,f]quinolizinium(6) with DNA was studied in detail in order to evaluate the influence of the shape of polycyclicquinolizinium ions on their DNA-binding properties. First, the synthesis and the thermally induceddimerization of 5a were reinvestigated because the preparation and isolation of the bromide salt of 5aaccording to literature procedures turned out to be problematic. The dibenzo[b,g]quinolizinium bromide[5a(Br)] tends to dimerize in solution with a highly selective and unprecedented formation of thecorresponding anti-head-to-head dimer. Nevertheless, it was observed that careful exclusion of bromideions from the reaction mixture suppresses the formation of the dimer. Moreover, the dimer may betransformed to the monomer by a remarkably rapid photoinduced electron-transfer reaction with1-methoxynaphthalene. The association of 5a and 6 with nucleic acids was investigated by spectrophotometric and spectrofluorimetric DNA titrations, CD and LD spectroscopy, DNA thermal denaturationstudies, and competition-dialysis techniques. Both dibenzoquinolizinium ions 5a and 6 exhibit anintercalative mode of binding to double-stranded DNA with moderate binding constants (K = 1−7 ×105 M-1) and a slight preference for association with GC-rich DNA regions. The structures of theintercalation complexes were calculated by molecular modeling methods. Competition-dialysis studiesreveal that the isomers 5a and 6 bind selectively to triple-helical DNA (poly[dA]-poly[dT]2) as comparedto selected synthetic and native double-stranded nucleic acids. Notably, the selectivity of the linear dibenzo[b,g]quinolizinium 5a toward triplex DNA is higher than the one of the angular derivative 6. In contrast,the DNA thermal denaturation studies reveal a higher stabilization of triple-helical DNA in the presenceof 6 (ΔTm3→2 = 28 °C at r = 0.5) as compared to the stabilization by 5a (ΔTm3→2 = 14 °C at r = 0.5).This comparison emphasizes the importance of the extended π system for the interaction of annelatedquinolizinium ions with DNA. Moreover, the comparison between 5a and 6 demonstrates the significantinfluence of the shape of the π system on the duplex- and triplex-stabilizing properties of thedibenzoquinolizinium ions.
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