Synthesis, DNA binding, nuclease activity and cytotoxic studies of a wheel-shaped octanuclear copper(II) complex based on 1,2,4-triazole
Dong-Dong Li, Na Zhang, Lin-Lin Dai, Zi-Bo Yang, Zun-Wei Tao
Applied Organmetallic Chemistry
The antitumor activity shown by many platinum complexes has produced a strong interest in research of new organometallic compounds. Among the metal compounds synthesized and tested, copper compounds have received considerable attention because of their cytotoxic activity against solid tumors. A novel wheel-shaped octanuclear copper(II) complex with a 1,2,4-triazole derivative ligand formulated as [Cu8L4](ClO4)8⋅11H2O (1) (L = 3,5-bis((bis(2-hydroxylethyl)amino)methyl)-4 H-1,2,4,-triazole-4-amine) has been synthesized and structurally characterized. In 1, eight Cu atoms are linked through 1,2,4-triazole units and alkoxide bridges to form a centrosymmetric octanuclear Cu(II) metallomacrocycle. The interaction of complex 1 with calf thymus DNA has been studied using UV absorption, fluorescence and circular dichroism spectroscopies, viscosity measurements and cyclic voltammetry. The apparent binding constant (kapp) value for 1 is 1.59 × 105 M−1. Furthermore, complex 1 displays efficient oxidative cleavage of supercoiled DNA in the presence of external agents, the rate constant for the conversion of supercoiled to nicked DNA being 2.67 × 10−5 s−1. Interestingly, cytotoxicity studies on the MCF-7 human breast cancer cell line show that the IC50 value of 1 is less than that of cisplatin for the same cell line, revealing that it has the potential to act as an effective metal-based anticancer drug.
Circular dichroism, Coordination chemistry, Biochemistry, Ligand binding, DNA structure