5,10,15,20-Tetrakis(4-N-methylpyridyl)porphyrinatopalladium(II) as a differentiation probe for sensing binding modes with B-DNA duplexes: Electronic MCD and CD spectra

We report our detailed electronic MCD, CD, and optical spectroscopic measurements and analysis of the porphyrin Soret (B₀) region of four-coordinate 5,10,15,20-tetrakis(4-N-methylpyridyl)porphyrinatopalladium(II), PdP(4), and its bound states with B-DNA duplexes poly(A-T)₂, poly(G-C)₂, and calf thymus DNA (CT DNA). For system PdP(4)/poly(A-T)₂ it was possible to conclude that the porphyrin is bound edge-on in the major groove, specifically at the 5′AT3′ site. For this orientation the porphyrin's electric dipole transition moments (edtm), μ_x (most perturbed direction) and μ_y (least perturbed direction), have tilt angles α ∼ 90° and ∼ 45°, respectively, relative to the helix axis. It was further concluded from the small shifts of B₀ optical and MCD band intensities and wavelengths and from the net MCD (+) A-term sign retention upon binding that the porphyrin's frontier pπ MOs (1a_1u 3a_2u 4e_g) are only weakly perturbed by the heterocyclic bases of poly(A-T)₂, and therefore that the LUMO (4e_g) splitting is less than the |1a_1u−3a_2u| energy separation, ΔHOMO, that is, ΔLUMO < ΔHOMO for the bound state in PdP(4)/poly(A-T)_2. For intercalation systems PdP(4)/poly(G-C)₂ and /CT DNA, with PdP(4) centered in the intercalation “pocket” and having two of its 4-N-methylpyridyls extending into each of the major and minor grooves, the edtms μ_x and μ_y were determined to be oriented perpendicular (γ ∼ 0°) and parallel (γ ∼ 90°) to the hydrogen bonds of the base pairs, respectively. Intercalation is characterized by a much stronger binding interaction, viz., the B₀ optical band and net MCD extrema wavelength shifts are relatively large, and the net MCD (+) A-term of PdP(4) is substantially quenched as it becomes the (−) pseudo-A-term of intercalated PdP(4)/poly(G-C)₂. This A-term sign reversal informs that the porphyrin MOs are so strongly perturbed by the GC base pairs that ΔLUMO > ΔHOMO, which gives rise to a (−) pseudo-A-term. Also, the findings demonstrate (1) the potential of PdP(4) as a sensitive, discriminating analytical probe of DNA sequences and (2) the diagnostic capability of the composite of five spectra [net MCD, CD, and optical of free and bound PdP(4)] in differentiating the site and sequence selectivity and preferred binding mode of this porphyrin. © 1999 John Wiley & Sons, Inc. Biospectroscopy 5: 179–188, 1999