DNA cleavage activity of VO(acac)2 and derivatives

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Abstract The DNA cleavage activity of several β-diketonate vanadyl complexes is examined. Vanadyl acetylacetonate, V IV O(acac) 2 , 1, shows a remarkable activity in degrading plasmid DNA in the absence of any activating agents, air and photoirradiation. The cleaving activity of several related complexes V IV O(hd) 2 (2, Hhd=3,5-heptanedione), V IV O(acac-NH 2) 2 (3, Hacac-NH 2 =acetoacetamide) and V IV O(acac-NMe 2) 2 (4, Hacac-NMe 2 =N,N-dimethylacetoacetamide) is also evaluated. It is shown that 2 exhibits an activity similar to 1, while 3 and 4 are much less efficient cleaving agents. The different activity of the complexes is related to their stability towards hydrolysis in aqueous solution, which follows the order 1~2 >> 3~4. The nature of the pH buffer was also found to be determinant in the nuclease activity of 1 and 2. In a phospate buffered medium DNA cleavage by these agents is much more efficient than in tris, hepes, mes or mops buffers. The reaction seems to take place through a mixed mechanism, involving the formation of reactive oxygen species (ROS), namely OH radicals, and possibly also direct cleavage at phosphodiester linkages induced by the vanadium complexes.