Synthesis, characterization and potent superoxide dismutase-like activity of novel bis(pyrazole)-2,2'-bipyridyl mixed ligand copper(II) complexes.
Eleven new complexes of Cu(II) chloride and nitrate with bis(pyrazol-1-yl)propane and bis[2-(pyrazol-1-yl)ethyl]ether ligands were prepared and characterized by spectral and electrochemical methods. X-Ray crystal structure determination of bis[2-(3,5-dimethylpyrazol-1-yl)ethyl]etherdinitratocopper revealed a hepta-coordinated structure with the bis(pyrazole) ligand coordinated in a tridentate NNO-fashion and both of the nitrate ions in a bidentate fashion. Reaction of Cu(II) nitrate complexes with 2,2'-bipyridyl led to the displacement of one of the nitrate ions into the outer sphere and the formation of mixed-ligand complexes. Mixed-ligand bipyridyl Cu(II) complexes demonstrated the highest superoxide dismutase (SOD)-like activity in a chemical superoxide anion-generating system, with IC(50) values in the low micromolar range. Density functional theory calculations showed that introduction of a bipypidyl ligand into the complexes dramatically lowered the lowest unoccupied molecular orbital (LUMO) energy level, which explains the increased SOD-like activity of these complexes compared to non-bipy species. These bipy complexes were also effective scavengers of reactive oxygen species generated by phagocytes (human neutrophils and murine bone marrow leukocytes) ex vivo. Thus, these bipy mixed-ligand complexes represent a promising class of SOD mimetics for future development.
Potapov
Andrei S
AS
Department of Chemistry, Altai State Technical University, Barnaul 656038, Russia.
Nudnova
Evgenia A
EA
Domina
Galina A
GA
Kirpotina
Liliya N
LN
Quinn
Mark T
MT
Khlebnikov
Andrei I
AI
Schepetkin
Igor A
IA
D015082:2,2'-Dipyridyl / Q000737:chemistry*; D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004583:Electrons; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011789:Quantum Theory; D013057:Spectrum Analysis; D013482:Superoxide Dismutase / Q000378:metabolism*
D016166:Free Radical Scavengers; D008024:Ligands; D009942:Organometallic Compounds; D015082:2,2'-Dipyridyl; D003300:Copper; D013482:Superoxide Dismutase