title: Experimental electron density study of a complex between copper(II) and the antibacterial quinolone family member ciprofloxacin.
abstract: An experimental charge density study of a 1 : 1 complex of Cu-cfx (cfx = ciprofloxacin), 1 [Cu(cfx)(H(2)O)(3)]SO4.2H(2)O, has been performed using single-crystal X-ray diffraction data collected at 100 K using conventional Mo Kalpha radiation. Metal-ligand (ML) bonds and hydrogen bonds (HBs) have been analysed using topological analysis of the electron density with the atoms in molecules (AIM) approach. The copper atom binds to two oxygen atoms in one end of the zwitterionic form of the cfx molecule, in addition to forming bonds with three water molecules, forming a square pyramidal coordination geometry. AIM decomposition of the experimental electron density establishes that the copper atom binds more strongly to the cfx molecule than to the water molecules, suggesting that the latter can be detached leaving behind a reactive, water-free Cu-cfx complex available for interaction with e.g. a macromolecular site. AIM analysis of the extensive hydrogen bond pattern reveals that the positively charged N-end of the zwitterionic cfx forms a relatively strong N-H-O hydrogen bond implying that this region of cfx may play an important role in the docking process in the active site. Visualisation and statistics of selected density derived properties on the molecular surface of the isolated cfx molecule vs its metal complexed counterpart points out regions of potential reactivity. The effect of the fluorine atom is to expand the negative region of the electrostatic potential, while the nitrogen end is heavily electropositive and willingly donates to--for molecular docking purposes--relatively strong hydrogen bonding. The Cu atom is highlighted as a potentially highly reactive site which is likely to interact strongly with any given negative ligand.
authors.affiliation: Department of Chemistry, University of Aarhus, Langelandsgade 140, DK-8000, Aarhus C.. jacobo@chem.au.dk
authors.forename: Jacob
authors.initials: J
authors.lastname: Overgaard
authors.forename: Iztok
authors.initials: I
authors.lastname: Turel
authors.forename: David E
authors.initials: DE
authors.lastname: Hibbs
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002939:Ciprofloxacin / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004583:Electrons; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry / Q000145:classification; D055672:Static Electricity
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D015363:Quinolones; D002939:Ciprofloxacin; D003300:Copper