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 monoc ation (MDAP), and N,N'-dimethyl-2,7-diazapyrenium dication (DMDAP) to calf thymus DNA has been studied with respect to molecular geometry an d thermodynamics. It is concluded from flow linear dichroism (LD) and induced circular dichroism (CD) spectra that the three diazapyrenes bi nd by intercalation to alternating AT as well as GC polynucleotide dup lexes, as indicated by strong interactions with the transitions of the nucleobases in conjunction with approximately perpendicular orientati ons 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. Thi s finding is interpreted in terms of a microscopic heterogeneity assoc iated with rotational mobility of the ligand in a tilted intercalation pocket, with the dication DMDAP having less rotational freedom than t he neutral DAP has. Other distinct differences between the three diaza pyrenes are revealed in their thermodynamic parameters of binding. DAP binds with a negative Delta H degrees (-9 kcal/mol) and a negative De lta S degrees (-7 cal/(mol K)), whereas the binding of the dication DM DAP is entropically driven (+43 cay(mol K)) but enthalpically disfavor ed (+5.2 kcal/mol), the monocation MDAP having an intermediate positio n (Delta H degrees = -3 kcal/mol, Delta S degrees = +12 cal/(mol K)).