title: In vitro and in vivo activity of a new unsymmetrical dinuclear copper complex containing a derivative ligand of 1,4,7-triazacyclononane: catalytic promiscuity of [Cu2(L)Cl3].
abstract: Here we present the synthesis of the dinuclear complex [Cu(II)2(L)Cl3] (1), where L is the deprotonated form of the 3-[(4,7-diisopropyl-1,4,7-triazacyclononan-1-yl)methyl]-2-hydroxy-5-methylbenzaldehyde ligand. The complex was characterized by single crystal X-ray diffraction, potentiometric titration, mass spectrometry, electrochemical and magnetic measurements, EPR, UV-Vis and IR. Complex 1 is able to increase the hydrolysis rate of the diester bis-(2,4-dinitrophenyl)phosphate (2,4-BDNPP) by a factor of 2700, and also to promote the plasmidial DNA cleavage at pH 6 and to inhibit the formazan chromophore formation in redox processes at pH 7. Using Saccharomyces cerevisiae (BY4741) as a eukaryotic cellular model, we observed that 1 presents reduced cytotoxicity. In addition, treatment of wild-type and mutant cells lacking Cu/Zn-superoxide dismutase (Sod1) and cytoplasmic catalase (Ctt1) with 1 promotes increased survival after H2O2 or menadione (O2˙(-) generator) stress, indicating that 1 might act as a Sod1 and Ctt1 mimetic. Considered together, these results support considerations regarding the dynamic behaviour of an unsymmetrical dinuclear copper(II) complex in solid state and in aqueous pH-dependent solution.
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil. vicentebra@hotmail.com
authors.forename: Vicente R
authors.initials: VR
authors.lastname: de Almeida
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Xavier
authors.forename: Renata E H M B
authors.initials: RE
authors.lastname: Osório
authors.forename: Luiza M
authors.initials: LM
authors.lastname: Bessa
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Schilling
authors.forename: Thiago G
authors.initials: TG
authors.lastname: Costa
authors.forename: Tiago
authors.initials: T
authors.lastname: Bortolotto
authors.forename: Angélica
authors.initials: A
authors.lastname: Cavalett
authors.forename: Frederico A V
authors.initials: FA
authors.lastname: Castro
authors.forename: Felipe
authors.initials: F
authors.lastname: Vilhena
authors.forename: Odivaldo C
authors.initials: OC
authors.lastname: Alves
authors.forename: Hernán
authors.initials: H
authors.lastname: Terenzi
authors.forename: Elis C A
authors.initials: EC
authors.lastname: Eleutherio
authors.forename: Marcos D
authors.initials: MD
authors.lastname: Pereira
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Haase
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Tomkowicz
authors.forename: Bruno
authors.initials: B
authors.lastname: Szpoganicz
authors.forename: Adailton J
authors.initials: AJ
authors.lastname: Bortoluzzi
authors.forename: Ademir
authors.initials: A
authors.lastname: Neves
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D002384:Catalysis; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D008280:Magnetics; D008968:Molecular Conformation; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013696:Temperature
chemical_list: D000975:Antioxidants; D056831:Coordination Complexes; D006571:Heterocyclic Compounds; D008024:Ligands; C075712:1,4,7-triazacyclononane; D003300:Copper; D004247:DNA; D013482:Superoxide Dismutase