title: The chemical biology of Cu(II) complexes with imidazole or thiazole containing ligands: Synthesis, crystal structures and comparative biological activity.
abstract: The synthesis and characterization of two copper(II) complexes containing 2-(2-pyridyl)benzimidazole (PyBIm) are reported with the biological activity of these two complexes and a third Cu(II) complex containing 2-(2-pyridyl)benzothiazole (PyBTh). Complex 1, [Cu(PyBIm)(NO3)(H2O)](NO3), is a four coordinate, distorted square planar species with one ligand (N,N), nitrate and water bound to Cu(II). The [Cu(PyBIm)3](BF4)2 complex (2) has distorted octahedral geometry with a 3:1 Py(BIm) ligand to metal ratio. The distorted trigonal bi-pyramidal geometry of compound 3, [Cu(PyBTh)2(H2O)](BF4)2, is comprised of two PyBTh ligands and one water. Biological activity of 1-3 has been assessed by analyzing DNA interaction, nuclease ability, cytotoxic activity and antibacterial properties. Complex 3 exhibits potent concentration dependent SC-DNA cleavage forming single- and double-nicked DNA in contrast to the weak activity of complexes 1 and 2. Mechanistic studies indicate that all complexes utilize an oxidative mechanism however 1 and 2 employ O2(-) as the principal reactive oxygen species while the highly active 3 utilizes (1)O2. The interaction between 1-3 and DNA was investigated using fluorescence emission spectroscopy and revealed all complexes strongly intercalate DNA with Kapp values of 2.65 × 10(6), 1.85 × 10(6) and 2.72 × 10(6)M(-1), respectively. Cytotoxic effects of 1-3 were examined using HeLa and K562 cells and show cell death in the micromolar range with the activity of 1 ≈ 2 and were slightly higher than 3. Similar reactivity was observed in the antibacterial studies with E. coli and S. aureus. A detailed comparative analysis of the three complexes is presented.
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Lewis
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Molly
authors.initials: M
authors.lastname: McDonald
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Scharbach
authors.affiliation: Department of Chemistry and Biochemistry, Union College, Schenectady, NY 12308, United States.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hamaway
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Plooster
authors.affiliation: Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Peters
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: D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D004587:Electrophoresis, Agar Gel; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008024:Ligands; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D008024:Ligands; D013844:Thiazoles; D003300:Copper
keywords: Antibacterial; Benzimidazole; Benzothiazole; Copper(II); DNA; Nuclease