Butenko Nataliya, Tomaz Ana Isabel, Nouri Ofelia, Escribano Esther, Moreno Virtudes, Gama Sofia, Ribeiro Vera, Telo João Paulo, Pesssoa João Costa, Cavaco Isabel
Departamento de Química, Bioquímica e Farmácia, Universidade do Algarve, Campus de Gambelas, Faro, Portugal.
J Inorg Biochem. 2009 Apr;103(4):622-32. doi: 10.1016/j.jinorgbio.2009.01.003. Epub 2009 Jan 18.
The DNA cleavage activity of several beta-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 approximately 2>>3 approximately 4. The nature of the pH buffer was also found to be determinant in the nuclease activity of 1 and 2. In a phosphate 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.
研究了几种β-二酮钒配合物的DNA切割活性。乙酰丙酮氧钒（V(IV)O(acac)(2)，1）在没有任何活化剂、空气和光照射的情况下，在降解质粒DNA方面表现出显著的活性。还评估了几种相关配合物V(IV)O(hd)(2)（2，Hhd = 3,5-庚二酮）、V(IV)O(acac-NH(2))(2)（3，Hacac-NH(2)=乙酰乙酰胺）和V(IV)O(acac-NMe(2))(2)（4，Hacac-NMe(2)=N,N-二甲基乙酰乙酰胺）的切割活性。结果表明，2表现出与1相似的活性，而3和4作为切割剂的效率要低得多。配合物的不同活性与其在水溶液中的水解稳定性有关，其顺序为1≈2>>3≈4。还发现pH缓冲液的性质对1和2的核酸酶活性起决定性作用。在磷酸盐缓冲介质中，这些试剂对DNA的切割比在三羟甲基氨基甲烷、羟乙基哌嗪乙磺酸、吗啉乙磺酸或3-(N-吗啡啉)丙磺酸缓冲液中更有效。该反应似乎通过一种混合机制发生，涉及活性氧（ROS）的形成，即羟基自由基，也可能涉及钒配合物诱导的磷酸二酯键的直接切割。
