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Preparation of Tetracationic Metalloporphyrin−Spermine Conjugates

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journal contribution
posted on 30.05.1997, 00:00 by Andreas Jakobs, Jean Bernadou, Bernard Meunier
The preparation of tetracationic metalloporphyrin precursors for the attachement to DNA binding molecules is reported. Based on a D4h tetrapyridylporphyrin, such precursors are more accessible than the classical tailored tricationic porphyrin derivatives used as DNA cleavers. meso-Tetrapyridylporphyrin was reacted with ethyl bromopentanoate and methyl iodide to afford a monofunctionalized ester derivative of 1 which was hydrolyzed to the corresponding acid 5. This acid was reacted with spermine and BOP to yield conjugates containing one (6) or two (7) porphyrin units that were metalated with Mn(II) salts to afford the metalloporphyrins 6−Mn and 7−Mn. Furthermore, 6−Mn was linked to 5 to yield a spermine conjugate 8 containing two porphyrin moieties, one of which was metalated. The DNA cleavage activity of these different metalloporphyrins was studied in the presence of KHSO5 with double-stranded ΦX174 DNA. Conjugate 5−Mn, the spermine containing compound 6−Mn, and compound 7−Mn which contained two porphyrin moieties showed cleavage activities similar to that of the parent DNA cleaver 1−Mn. The porphyrin conjugate 8 which contained one metalated and one nonmetalated porphyrin had half the efficiency of 1−Mn. None of the synthesized compounds were able to induce direct double-strand breaks in the experimental conditions used.