title: Synthesis, characterization, crystal structures and biological activity of set of Cu(II) benzothiazole complexes: artificial nucleases with cytotoxic activities.
abstract: 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)∙CH3OH (1∙CH3OH), Cu(8OHQ(oBt))Cl2∙CH3OH (2∙CH3OH), Cu(8OQ(oBt))Cl(CH3OH)∙CH3OH (3∙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 1.47×10(7)M(-1) and 3.09×10(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 10μM. The nuclease activity of complexes 1-3 is primarily dependent on (1)O2 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.
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Ramsey A
authors.initials: RA
authors.lastname: Steiner
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: David
authors.initials: D
authors.lastname: Foreman
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Han X
authors.initials: HX
authors.lastname: Lin
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, United States.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Carney
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Fox
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, United States.
authors.forename: Lynne
authors.initials: L
authors.lastname: Cassimeris
authors.affiliation: Department of Chemistry, Vassar College, Poughkeepsie, NY 12604, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tanski
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States. Electronic address: tylerl@union.edu.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Tyler
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D056831:Coordination Complexes / Q000008:administration & dosage / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D013830:Thiadiazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D013830:Thiadiazoles; C015700:benzo-1,2,3-thiadiazole; D003300:Copper
keywords: Benzothiazole; Copper(II); Nuclease; Protonated phenol; Quinoline