title: Copper(II) interacting with the non-steroidal antiinflammatory drug flufenamic acid: structure, antioxidant activity and binding to DNA and albumins.
abstract: Copper(II) complexes with the non-steroidal antiinflammatory drug flufenamic acid (Hfluf) in the presence of N,N-dimethylformamide (DMF) or nitrogen donor heterocyclic ligands (2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2'-bipyridine (bipy) or pyridine (py)) have been synthesized and characterized. The crystal structures of [Cu2(fluf)4(DMF)2], 1, and [Cu(fluf)(bipyam)Cl], 2, have been determined by X-ray crystallography. Density functional theory (DFT) (CAM-B3LYP/LANL2DZ/6-31G**) was employed to determine the structure of complex 2 and its analogues (complexes [Cu(fluf)(phen)Cl], 3, [Cu(fluf)(bipy)Cl], 4 and [Cu(fluf)2(py)2], 5). Time-dependent DFT calculations of doublet-doublet transitions show that the lowest-energy band in the absorption spectrum of 2-5 has a mixed d-d/LMCT character. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA with [Cu(fluf)(bipy)Cl] exhibiting the highest binding constant to CT DNA. The complexes can bind to CT DNA via intercalation as concluded by studying the cyclic voltammograms of the complexes in the presence of CT DNA solution and by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have shown that the complexes can displace the DNA-bound EB suggesting strong competition with EB. Flufenamic acid and its Cu(II) complexes exhibit good binding affinity to human or bovine serum albumin protein with high binding constant values. All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity with [Cu(fluf)(phen)Cl] being the most active.
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Charikleia
authors.initials: C
authors.lastname: Tolia
authors.forename: Athanassios N
authors.initials: AN
authors.lastname: Papadopoulos
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Raptopoulou
authors.forename: Vassilis
authors.initials: V
authors.lastname: Psycharis
authors.forename: Claudio
authors.initials: C
authors.lastname: Garino
authors.forename: Luca
authors.initials: L
authors.lastname: Salassa
authors.forename: George
authors.initials: G
authors.lastname: Psomas
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D005439:Flufenamic Acid / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding
chemical_list: D000418:Albumins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005439:Flufenamic Acid; D003300:Copper; D004247:DNA