Synthesis, characterization, crystal structures and biological activity of set of Cu(II) benzothiazole complexes: Artificial nucleases with cytotoxic activities

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)center dot CH3OH (1 center dot CH3OH), Cu(80HQ(oBt))Cl-2 center dot CH3OH (2 center dot CH3OH), Cu(8OQ(oBt))Cl(CH3OH)center dot CH3OH (3 center dot CH3OH) and [Cu(8OH(1/2)Q(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 K-app values of 1.47 x 10(7)M(-1) and 3.09 x 10(7) 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 mu W. The nuclease activity of complexes 1-3 is primarily dependent on O-1(2) species while center dot 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. (C) 2014 Elsevier Inc. All rights reserved.