Synthesis, characterization, crystal structures and biological activity of set of Cu(II) benzothiazole complexes: Artificial nucleases with cytotoxic activities
详细信息 查看全文
- 作者：Ramsey A. Steinera ; David Foremana ; Han X. Lina ; Bruce K. Carneyb ; Kristin M. Foxa ; Lynne Cassimerisb ; Joseph M. Tanskic ; Laurie A. Tylera ; tylerl@union.edu" class="auth_mail
- 关键词：Benzothiazole ; Quinoline ; Copper(II) ; Protonated phenol ; Nuclease
- 刊名：Journal of Inorganic Biochemistry
- 出版年：August 2014
- 年：2014
- 卷：137
- 期：Complete
- 页码：1-11
- 全文大小：1450 K
文摘
A series of Cu(II) complexes with ligand frames based on quinoline derivatives appended with a benzothiazole substituent has been isolated. The complexes, Cu(Q(oBt))(NO3)2(H2O)鈭機H3OH (1 鈭?#xA0;CH3OH), Cu(8OHQ(oBt))Cl2 鈭?#xA0;CH3OH (2 鈭?#xA0;CH3OH), Cu(8OQ(oBt))Cl(CH3OH)鈭機H3OH (3 鈭?#xA0;CH3OH) and [Cu(8OH1/2Q(oBt))(CH3OH)(NO3)]2(NO3) (4) have been characterized by single crystal X-ray diffraction, IR and UV-visible spectroscopies, and elemental analysis. The ligand frame within the set of complexes differs in the substituent on the quinoline ring: complex 1 remains unsubstituted at this position while complexes 2–4 have a substituted 
OH group. In complex 2, the bound phenol remains protonated while in 3 it is a phenolato group. Complex 4 contains two complexes within the unit cell and one NO3− giving rise to an overall ‘half-protonation’. The interaction between complexes 1–3 with CT-DNA was investigated using fluorescence emission spectroscopy and revealed 2 and 3 strongly intercalate DNA with Kapp values of 1.47 × 107 M− 1 and 3.09 × 107 M− 1, respectively. The ability of complexes 1–3 to cleave SC-DNA was monitored using gel electrophoresis. Each complex exhibits potent, concentration dependent nuclease activity forming single and double-nicked DNA as low as 10 渭M. The nuclease activity of complexes 1–3 is primarily dependent on 1O2 species while ·OH radicals play a secondary role in the cleavage by complexes 2 and 3. The cytotoxic effects of 1–3 were examined using HeLa cells and show cell death in the micromolar range. The distribution of cell cycle stages remains unchanged when complexes are present indicating DNA damage may be occurring throughout the cell cycle.
OH group. In complex 2, the bound phenol remains protonated while in 3 it is a phenolato group. Complex 4 contains two complexes within the unit cell and one NO3− giving rise to an overall ‘half-protonation’. The interaction between complexes 1–3 with CT-DNA was investigated using fluorescence emission spectroscopy and revealed 2 and 3 strongly intercalate DNA with Kapp values of 1.47 × 107 M− 1 and 3.09 × 107 M− 1, respectively. The ability of complexes 1–3 to cleave SC-DNA was monitored using gel electrophoresis. Each complex exhibits potent, concentration dependent nuclease activity forming single and double-nicked DNA as low as 10 渭M. The nuclease activity of complexes 1–3 is primarily dependent on 1O2 species while ·OH radicals play a secondary role in the cleavage by complexes 2 and 3. The cytotoxic effects of 1–3 were examined using HeLa cells and show cell death in the micromolar range. The distribution of cell cycle stages remains unchanged when complexes are present indicating DNA damage may be occurring throughout the cell cycle.