DNA binding properties of 2,7-diazapyrene and its N-methylated cations studied by linear and circular dichroism spectroscopy and calorimetry

The binding of 2,7-diazapyrene (DAP), N-methyl-2,7-diazapyrenium monocation (MDAP), and N,N'-dimethyl-2,7-diazapyrenium dication (DMDAP) to calf thymus DNA has been studied with respect to molecular geometry and thermodynamics. It is concluded from flow linear dichroism (LD) and induced circular dichroism (CD) spectra that the three diazapyrenes bind by intercalation to alternating AT as well as GC polynucleotide duplexes, as indicated by strong interactions with the transitions of the nucleobases in conjunction with approximately perpendicular orientations of the in-plane symmetry axes relative to the DNA helix axis. The reduced LD (LDt = LD/A(iso)) of the DNA complexes is characterized by marked fine structure, decreasing in the order DAP > MDAP > DMDAP. This finding is interpreted in terms of a microscopic heterogeneity associated with rotational mobility of the ligand in a tilted intercalation pocket, with the dication DMDAP having less rotational freedom than the neutral DAP has. Other distinct differences between the three diazapyrenes are revealed in their thermodynamic parameters of binding. DAP binds with a negative Delta H degrees (-9 kcal/mol) and a negative Delta S degrees (-7 cal/(mol K)), whereas the binding of the dication DMDAP is entropically driven (+43 cay(mol K)) but enthalpically disfavored (+5.2 kcal/mol), the monocation MDAP having an intermediate position (Delta H degrees = -3 kcal/mol, Delta S degrees = +12 cal/(mol K)).