EPR study of copper(II) complexes of hydroxysalen derivatives in order to be used in the DNA cleavage.

Two series of functionalized hydroxy-salen-copper(II) complexes with various side chain lengths have been synthesized. The first one is characterised by amino side chain protected by the tert-butyloxycarbonyl group (Boc) whereas, the second series is obtained by removal of the Boc-protecting group under acidic conditions and formation instead of it an ammonium salt. EPR studies were carried out on the copper(II) complexes. EPR signals attributed to monomers and dimers of Cu2+ species were evidenced. Determination of the copper(II) environment in each complex was attempted using all the experimental results. Square planar and tetrahedral symmetries were found for the copper(II) monomers. From the fine structure observed for the pair signal, the distance between the Cu2+ ions in the pair has been calculated (3.9-4.3A). From these values, it seems that the formation of pairs is obtained by a face-to-face bimolecular association.

DNA modification by oxovanadium(IV) complexes of salen derivatives.

Oxovanadium(IV) complexes of hydroxysalen derivatives have been prepared and tested as DNA reactive agents. The nuclease activity has been investigated under oxidative or reducing conditions, on the basis of the various oxidation states of vanadium: V(III), V(IV) and V(V). In the absence of an activating agent, none of the compounds tested was able to induce cleavage of DNA, whereas in the presence of mercaptopropionic acid (MPA) or Oxone the four complexes induced DNA modifications. Under both conditions, the para-hydroxy complex was found to be the most active compound. Reaction of these salen complexes with DNA occurs essentially at guanine residues and is more efficient in the presence of Oxone than under reducing conditions. The extent of Oxone-mediated DNA oxidation by the four vanadyl complexes was clearly superior to VOSO(4) and was observed without piperidine treatment. EPR studies provided information on the reactive metal-oxo species involved under each conditions and a mechanism of reaction with DNA is discussed.