The design of specific DNA cleavers is a growing field of research for several reasons: (i) DNA is the biological target of a large number of antitumor agents which are able to cleave double-stranded nucleic acids, bleomycin,* 1 neocarzinostatin,2 and enediyne molecules,3 (ii) transition metal complexes linked to a DNA recognizing molecule (intercalating agents,4 peptides,5 or oligonucleotides6) are also able to cleave selectively single-or double-stranded nucleic acids, and (iii) some of these hybrid molecules, "DNA cleaver-vector", might have a future as antiviral or antitumoral agents.7 Cationic manganese-porphyrin complexes are among the efficient DNA cleavers because of their affinity for nucleic acids and their capacity to oxidize the sugar carbon-hydrogen bonds of deoxyribose units.8 Mechanistic studies on DNA breaks mediated by cationic manganese-porphyrins strongly suggest that high-valent manganese-oxo species might be responsible for DNA cleavage instead of diffusible oxygen species like hydroxyl radicals.8•9 Such metal-oxo species were also proposed for "activated bleomycin", an antitumoral antibiotic able to cleave DNA.la'cl°DNA cleavage selectivity can be modulated by linking the tris(methylpyridiniumyl)porphyrinatomanganese motif to different vectors: an intercalating agent like 9-methoxyellipticine11 or an oligonucleotide.12 This DNA cleaver exhibits also an anti-HIV activity alone or linked to 9-methoxyellipticine.13 For these different reasons, we decided to undergo the preparation of a series of water-soluble, cationic porphyrin ligands based on the tris(methylpyridiniumyl)porphyrin motif (Table I). All these unsymmetric porphyrins contain a * Author to whom correspondence should be addressed.(1) (a) Hecht, S.

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