Interaction of cationic porphyrins with DNA: importance of the number and position of the charges and minimum structural requirements for intercalation.
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.
Sari
M A
MA
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (UA 400 CNRS), Université René Descartes, Paris, France.
Battioni
J P
JP
Dupré
D
D
Mansuy
D
D
Le Pecq
J B
JB
D000595:Amino Acid Sequence; D000818:Animals; D002412:Cations; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000187:drug effects; D004735:Energy Transfer; D004996:Ethidium / Q000494:pharmacology; D008969:Molecular Sequence Data; D011166:Porphyrins; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013950:Thymus Gland / Q000378:metabolism
D002412:Cations; D011166:Porphyrins; D004247:DNA; D004996:Ethidium