Phosphate diester hydrolysis and DNA damage promoted by new cis-aqua/hydroxy copper(II) complexes containing tridentate imidazole-rich ligands.
The tridentate Schiff base [(2-(imidazol-4-yl)ethyl)(1-methylimidazol-2-yl)methyl)imine (HISMIMI) and its reduced form HISMIMA were synthesized and characterized, as well their mononuclear cis-dihalo copper(II) complexes 1 and 2, respectively. In addition, the dinuclear [CuII(mu-OH)2CuII](2+) complexes (3) and (4) obtained from complexes 1 and 2, respectively, were also isolated and characterized by several physicochemical techniques, including magnetochemistry, electrochemistry, and EPR and UV-vis spectroscopies. The crystal structures of 1 and 2 were determined by X-ray crystallography and revealed two neutral complexes with their tridentate chelate ligands meridionally coordinated. Completing the coordination spheres of the square-pyramidal structures, a chloride ion occupies the apical position and another is bonded in the basal plane. In addition, complexes 1 and 2 were investigated by infrared, electronic, and EPR spectroscopies, cyclic voltammetry, and potentiometric equilibrium studies. The hydrolytic activity on phosphate diester cleavage of 1 and 2 was investigated utilizing 2,4-BDNPP as substrate. These experiments were carried out at 50 degrees C, and the data treatment was based on the Michaelis-Menten approach, giving the following kinetic parameters (complex 1/complex 2): vmax (mol L(-1) s(-1))=16.4x10(-9)/7.02x10(-9); KM (mol L(-1))=17.3x10(-3)/3.03x10(-3); kcat (s(-1))=3.28x10(-4)/1.40x10(-4). Complex 1 effectively promoted the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions, with a rate constant of 0.28 h(-1) for the decrease of form I, which represents about a 10(7) rate increase compared with the estimated uncatalyzed rate of hydrolysis.
Scarpellini
Marciela
M
Laboratório de Bioinorgânica e Cristalografia, Departamento de Química, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Neves
Ademir
A
Hörner
Rosmari
R
Bortoluzzi
Adailton J
AJ
Szpoganics
Bruno
B
Zucco
César
C
Nome Silva
René A
RA
Drago
Valderes
V
Mangrich
Antônio S
AS
Ortiz
Wilson A
WA
Passos
Wagner A C
WA
de Oliveira
Maurício C B
MC
Terenzi
Hernán
H
D000693:Anaerobiosis; D000818:Animals; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D004952:Esters / Q000737:chemistry; D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D010957:Plasmids / Q000235:genetics; D011199:Potentiometry; D013055:Spectrophotometry, Infrared
D004952:Esters; D007093:Imidazoles; D007202:Indicators and Reagents; D008024:Ligands; D009942:Organometallic Compounds; D010710:Phosphates; D003300:Copper; D004247:DNA