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DNA modification by oxovanadium(IV) complexes of salen derivatives

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Abstract

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: VIII, VIV and VV. 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 VOSO4 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.

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Abbreviations

BPE buffer:

bis-phosphate EDTA buffer

DMPO:

5,5′-dimethylpyrroline N-oxide

DMS:

dimethyl sulfate

HFS:

hyperfine structure

Lin:

linear

MPA:

3-mercaptopropionic acid

Nck:

nicked

salen:

(salicylidene)ethylenediamine

Sc:

supercoiled

TBE buffer:

tris-borate EDTA buffer

Tris:

tris(hydroxymethyl)aminomethane

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Acknowledgements

This work was supported by grants (to C.B.) from the Ligue Nationale Contre le Cancer (Equipe labellisée LA LIGUE) and (to J-L.B.) from the CNRS.

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Correspondence to Jean-Luc Bernier.

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Verquin, G., Fontaine, G., Bria, M. et al. DNA modification by oxovanadium(IV) complexes of salen derivatives. J Biol Inorg Chem 9, 345–353 (2004). https://doi.org/10.1007/s00775-004-0529-0

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