title: Copper-1,10-phenanthroline complexes binding to DNA: structural predictions from molecular simulations.
abstract: Copper-1,10-phenanthroline (phen) complexes Cu(phen)(2)(), Cu(2-Clip-phen), and Cu(3-Clip-phen) (Clip = a serinol bridge between the phen parts) are typically employed as DNA-cleaving agents and are now becoming increasingly important for building multifunctional drugs with improved cytotoxic properties. For instance, Cu(3-Clip-phen) has been combined with distamycin-like minor-groove binders and cisplatin-derivatives, leading to promising results. Density Functional Theory (DFT) and docking calculations as well as molecular dynamics (MD) simulations were performed to describe the mode of binding to DNA of these complexes. Our data suggest the minor-groove binding to be more probable than (partial) intercalation and major-groove binding. In addition, it was found that a combination of factors including planarity, van der Waals interactions with DNA, and structural complementarities may be the key for the cleavage efficiency of these copper complexes.
authors.affiliation: SISSA, via Beirut 4, I-0 I-34014 Trieste, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Robertazzi
authors.forename: Attilio Vittorio
authors.initials: AV
authors.lastname: Vargiu
authors.forename: Alessandra
authors.initials: A
authors.lastname: Magistrato
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggerone
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
authors.forename: Paul
authors.initials: P
authors.lastname: de Hoog
authors.forename: Jan
authors.initials: J
authors.lastname: Reedijk
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D010618:Phenanthrolines / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory
chemical_list: D009942:Organometallic Compounds; D010618:Phenanthrolines; C464760:copper-1,10-phenanthroline; D004247:DNA