Targeting abasic site-containing DNA with annelated quinolizinium derivatives: the influence of size, shape and substituentsElectronic supplementary information (ESI) available: Synthesis of quinolizinium derivatives; photometric and fluorimetric titration spectra, DNA melting curves. See DOI: 10.1039/c3ob42140f

The interactions of regular DNA and abasic site-containing DNA (AP-DNA) with quinolizinium ( 1a ), the linearly fused benzo[ b ]quinolizinium ( 2a ), the angularly fused benzo[ a ]quinolizinium ( 3a ), benzo[ c ]quinolizinium ( 4a ), and dibenzo[ a , f ]quinolizinium ( 5a ) as well as derivatives thereof were studied with photometric and viscosimetric titrations (regular DNA), fluorimetric titrations and thermal DNA denaturation experiments (regular DNA and AP-DNA). Whereas the parent quinolizinium ion ( 1a ) and the benzo-annelated derivatives 2a , 3a and 4a exhibit no significant affinity to AP-DNA, additional benzo-annelation in 5a leads to an increased selective stabilization of AP-DNA by this ligand. Hence, the latter compound represents the first example of a ligand that does not require ancillary substituents for efficient AP-DNA stabilization. In addition, studies of derivatives with varied substitution patterns revealed an impact of substituents on the stabilization of the AP-DNA. We discovered that a chloro substituent affects the propensity of a ligand to bind to AP-DNA in a similar way as the methyl substituent and may be employed complementary to the known methyl effect to increase the binding affinity of a ligand. A comparative analysis showed that the type and degree of annelation as well as methyl or chloro-substitution are relevant structural features that determine the interactions of quinolizinium derivatives with abasic site-containing DNA.