Preparation of Tetracationic Metalloporphyrin−Spermine Conjugates

The preparation of tetracationic metalloporphyrin precursors for the attachement to DNA binding molecules is reported. Based on a D 4 h 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 KHSO 5 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.