Interaction of cationic porphyrins with DNA: importance of the number and position of the charges and minimum structural requirements for intercalation

Abstract

Thirty-three porphyrins or metalloporphyrins corresponding to the general formula [meso-[N-methyl-4(or 3 or 2)-pyridiniumyl]n(aryl)4-nporphyrin]M (M = H2, CuII, or ClFeIII), with n = 2-4, have been synthesized and characterized by UV-visible and 1H NMR spectroscopy and mass spectrometry. These porphyrins differ not only in the number (2-4) and position of their cationic charges but also in the steric requirements to reach even temporarily a completely planar geometry. In particular, they contain 0, 1, 2, 3, or 4 meso-aryl substituents not able to rotate. Interaction of these porphyrins or metalloporphyrins with calf thymus DNA has been studied and their apparent affinity binding constants have been determined by use of a competition method with ethidium bromide which was applicable not only for all the free base porphyrins but also for their copper(II) or iron(III) complexes. Whatever their mode of binding may be, their apparent affinity binding constants were relatively high (Kapp between 1.2 x 10(7) and 5 x 10(4) M-1 under our conditions), and a linear decrease of log Kapp with the number of porphyrin charges was observed. Studies of porphyrin-DNA interactions by UV and fluorescence spectroscopy, viscosimetry, and fluorescence energy transfer experiments showed that not only the tetracationic meso-tetrakis[N-methyl-4(or 3)-pyridiniumyl]porphyrins, which both involved four freely rotating meso-aryl groups, but also the corresponding tri- and dicationic porphyrins were able to intercalate into calf thymus DNA. Moreover, the cis dicationic meso-bis(N-methyl-2-pyridiniumyl)diphenylporphyrin, which involved only two freely rotating meso-aryl groups in a cis position, was also able to intercalate. The other meso-(N-methyl-2-pyridiniumyl)n(phenyl)4-nporphyrins, which involved either zero, one, or two trans freely rotating meso-aryl groups, could not intercalate into DNA. These results show that only half of the porphyrin ring is necessary for intercalation to occur.

Syntheses and DNA binding of new cationic porphyrin–tetrapeptide conjugates

“…Increasing relative base pair concentration is followed by hypochromism and red shift of the spectra. These overall spectral changes are typical for the cationic porphyrin-DNA binding described before [35][36][37].…”

“…Porphyrins that contact closely with DNA bases are characterized by a clear increase of their fluorescence quantum yields for an excitation around 260 nm, corresponding to an energy transfer from DNA bases to porphyrins [35]. This phenomenon can be considered as a criterion for intercalation.…”

CD and DSC Investigation of Individual and Complex Influence of Meso-Tetra(4-Oxiethylpyridil) Porphyrin (TOEPyP4) and Its Zn-Complex on DNA

“…This mechanism of DNA conformation changes that is caused by intercalation of TOEPyP4 also gives us a possibility to explain those strong CD changes, which are observed in case of binding of Zn-porphyrin to DNATOEPyP4 complex (Figure 3(a)) and formation of triple complex at addition of both porphyrins into the DNA mixture (Figure 4). In case of addition of TOEPyP4 into the solution containing the DNA-Zn-porphyrin complex, the added porphyrin preferably intercalates into the GC rich sites, because the binding constant of TOEPyP4 is more than binding constant of ZnTOEPyP4 [24][25][26]. This addition causes changes in DNA conformation, which leads to release of Zn-porphyrin from the binding sites.…”

Thermodynamic and spectroscopic study on the binding of interaction anionic phthalocyanine with calf thymus DNA

“…Like intercalators, groove binders have proven clinical utility as anti-cancer and antibacterial agents [15]. A great deal of works [6,12,17,18,23,25,28] have been studied on the interactions of cationic porphyrins with DNA as the formation of porphyrin-DNA complexes, one of the most important steps in effective therapeutic treatment of tumor activity, is known to be facilitated by the electrostatic attractions between the periphery of cationic porphyrins and the anionic phosphate backbone of DNA. Actually, cationic porphyrins are considered as double functional compounds that strongly bind to DNA and photodynamically modify the target site of a DNA molecule by a mechanism similar to that of anti-cancer antibiotics such as bleomycin and daunomycin based on the DNA cleavage [2,14,22].…”