PREPARATION OF TETRACATIONIC METALLOPORPHYRIN - SPERMINE CONJUGATES

The preparation of tetracationic metalloporphyrin precursors for the a ttachement to DNA binding molecules is reported. Based on a D-4h tetra pyridylporphyrin, such precursors are more accessible than the classic al tailored tricationic porphyrin derivatives used as DNA cleavers. me so-Tetrapyridylporphyrin was reacted with ethyl bromopentanoate and me thyl iodide to afford a monofunctionalized ester derivative of 1 which was hydrolyzed to the corresponding acid 5. This acid was reacted wit h spermine and BOP to yield conjugates containing one (6) or two (7) p orphyrin units that were metalated with Mn(II) salts to afford the met alloporphyrins 6-Mn and 7-Mn. Furthermore, 6-Mn was linked to 5 to yie ld a spermine conjugate 8 containing two porphyrin moieties, one of wh ich was metalated. The DNA cleavage activity of these different metall oporphyrins was studied in the presence of KHSO5 with double-stranded phi X174 DNA. Conjugate 5-Mn, the spermine containing compound 6-Mn, a nd compound 7-Mn which contained two porphyrin moieties showed cleavag e activities similar to that of the parent DNA cleaver 1-Mn. The porph yrin conjugate 8 which contained one metalated and one nonmetalated po rphyrin had half the efficiency of 1-Mn. None of the synthesized compo unds were able to induce direct double-strand breaks in the experiment al conditions used.