title: Density functional theory studies on copper phenanthroline complexes.
abstract: Density functional theory calculations have been employed to investigate the role of structural properties of copper phenanthroline complexes for DNA-cleavage activity. Structural changes imposed on the coordination geometries of Cu(phen)(2)(+,2+) (phen = 1,10-phenanthroline) linked by a serinol bridge (abbreviated as Clip) were studied, as well as their energetic profiles. Our calculations show that structures of these copper complexes (in this work named as clipped complexes) strongly depend on the position of the link, rather than on the copper oxidation state. Ionization energies slightly differ among the three selected complexes, while inner-sphere reorganization energies more markedly depend on the serinol link. However, the relative rates of the redox reaction of Cu(phen)(2), Cu(2-Clip-phen), and Cu(3-Clip-phen) were found not to correlate with their relative DNA-cleavage activity experimentally observed. Thus, the serinol link mainly affects the structural properties of copper phenanthroline complexes rather than their electronic properties. Docking simulations of clipped and nonclipped Cu(I) phenanthroline complexes on a DNA 16mer, d[CGCTCAACTGTGATAC](2), were finally performed to assess how different structural properties could affect the formation of DNA adducts. This analysis revealed that the most stable adducts of Cu(phen)(2+) and Cu(3-Clip-phen)(+) with DNA bind in the minor groove, whereas Cu(2-Clip-phen)(+) binds preferentially into the major groove.
authors.affiliation: International School for Advanced Studies and CNR-INFM-Democritos National Simulation Center, Trieste, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Robertazzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Magistrato
authors.forename: Paul
authors.initials: P
authors.lastname: de Hoog
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Jan
authors.initials: J
authors.lastname: Reedijk
mesh_terms: D003198:Computer Simulation; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D053837:DNA Cleavage; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008962:Models, Theoretical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry*; D011485:Protein Binding; D012984:Software; D013816:Thermodynamics
chemical_list: D008024:Ligands; D010618:Phenanthrolines; D003300:Copper; D004247:DNA; D010100:Oxygen