Synthesis, characterization and potent DNA-cleaving activity of copper(II)-complexed berberine carboxylate
2012
Chen, Jin-Xiang | Lin, Wei-Er | Chen, Ming-Zhen | Zhou, Chun-Qiong | Lin, Yan-Ling | Chen, Ming | Jiang, Zhi-Hong | Chen, Wen-Hua
9-O-(4-carboxybenzyl)berberine (CBB) 1 was synthesized from the reaction of berberrubine with methyl 4-(bromomethyl)benzoate and subsequent hydrolysis. Its Cu(II) complex 2 was prepared from the reaction with Cu(NO₃)₂·3H₂O, and established as [Cu(CBB)₂](NO₃)₂·2H₂O by means of ¹H NMR, UV, IR, elemental analysis and TGA measurements. Agarose gel electrophoresis study on the cleavage of plasmid pBR322 DNA indicated that complex 2 was capable of efficiently cleaving DNA under physiological conditions, most probably via an oxidative mechanistic pathway involving the formation of singlet oxygen as the reactive species. Kinetic assay afforded the maximal first-order rate constant kₘₐₓ of 2.41h⁻¹ and Michaelis constant KM of 2.64mM, respectively, representing ca. 10⁸-fold acceleration in the cleavage. This catalytic efficacy is attributed to the Cu(II)-assisted formation of dimeric species, in which the two berberine subunits cooperatively bind to DNA, whereas the carboxylate-coordinated Cu(II) moiety functions as the cleavage-active center.
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