DNA Binding Studies of a New Dicationic Porphyrin. Insights into Interligand Interactions

Abstract

Cationic porphyrins have an affinity for DNA and potential for applications in the fields of photodynamic therapy and cellular imaging. This report describes a new dicationic porphyrin, 5,15-dimethyl-10,20-di(N-methylpyridinium-4-yl)porphyrin, abbreviated H2tMe2D4. Although tetrasubstituted, H2tMe2D4 presents modest steric requirements and forms in reasonable yield by a "2+2" synthetic method. Accordingly, studies of the zinc(II)- and copper(II)-containing derivatives, Zn(tMe2D4) and Cu(tMe2D4), have also been possible. Methods used to characterize DNA-binding motifs include absorption, emission, linear, and circular dichroism spectroscopies, as well as viscometry. An unusually detailed picture of porphyrin uptake emerges. As the ratio of DNA to porphyrin increases during a typical titration, H2tMe2D4 or Cu(tMe2D4) initially aggregates on the host and then shifts to intercalative binding at close quarters before finally dispersing into non-interacting intercalation sites of the host. Emission studies of the copper(II) porphyrin have been very valuable. The existence of a measurable signal is diagnostic of intercalative binding, and the saturation behavior establishes that internalization typically monopolizes approximately three base pairs. In the moderate loading regime, emission data are most telling because dipole-dipole interactions between near-neighbor porphyrins tend to confuse other spectroscopic assays. The third ligand, Zn(tMe2D4), behaves differently in that the uptake is a strictly cooperative process. The mode of binding also varies with the base content of the DNA host. When the DNA is rich in A=T base pairs, the porphyrin remains five-coordinate and binds externally; however, Zn(tMe2D4) loses its axial ligand and binds by intercalation if the host contains only G[triple bond]C base pairs.

Porphyrin–DNA conjugates: porphyrin induced adenine–guanine homoduplex stabilization and interduplex assemblies

“…The axial ligand together with increased hydrophilicity and nonplanarity of zinc(II)porphyrin (zinc atom is ∼0.2 Å above the N4 plane) most likely hindered effective π-π interactions between zinc porphyrin and the adjacent adenine-guanine base pair. 48 Annealing CD experiments (cooling rate 0.5 °C min −1 ) in the presence of 100 mM NaCl revealed that the DNA (260 nm) and Soret band (441 nm) CD signals started to appear when the temperature decreased below 30 °C (Fig. S35 †).…”

Spectroscopic investigation on the effect of pairing anions in imidazolium-based ionic liquids on the J-aggregation of meso-tetrakis-(4-sulfonatophenyl)porphyrin in aqueous solution

“…in ILs based on steady-state and the picosecond time-resolved fluorimetry [1][2][3][4][5][6][7][8][9]. Because of the importance of water-soluble porphyrins and metalloporphyrins in bioscience [10][11][12][13][14], material science [15][16][17], etc., the J-aggregation of meso-tetrakis-(4-sulfonatophenyl)porphyrin (TPPS) is studied in pyridium [18,19] or imidazolium-based [20] ionic liquid solutions and we have previously found that TPPS could form efficiently J-aggregates in pure acidic ILs 1-butylimidazolium tetrafluoroborate (HBIMBF 4 ), but could not form J-aggregates in pure acidic 1-butylimidazolium p-toluenesulfonate (HBIMTS) [20]. Two kinds of ILs possess the same cation but different anions.…”

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

“…Porphyrins designed to target DNA can be symmetrical molecules with four identical meso substituents or not [64,[72][73][74]. These dissymmetric porphyrins contributed to a better understanding of structural factors governing DNA binding such as charge number and position or steric constraints.…”