Physical properties of dinitrosyl iron complexes with thiol-containing ligands in relation with their vasodilator activity.
When studying the vasodilator activity of dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO donors, it should be taken into consideration that these complexes depending on the content of thiols in the environment can occur in either of two forms that differ by their EPR, gamma-resonance and optical characteristics and also by their vasodilator effect on isolated blood vessels. The more stable diamagnetic form appears at the ratio Fe2+:RS- = 1:2. It reversibly dissociates to the monomeric paramagnetic form [(RS-)2Fe+(NO+)2] on increasing the thiol content to the level 20-times and more exceeding the quantity of iron. It is suggested that stabilization of the dimeric form is provided by formation of RS(-)-NO+ bonds between monomeric components of the dimer. This process is favored by a corresponding orientation of the monomers relative to each other. A high stability of the DNIC dimeric form correlates with more prolonged vasodilator effect of this complex as an NO source. Replacement of cysteine by reduced glutathione in dimeric and monomeric forms of DNIC increases both stability of the complexes and the duration of their vasodilator effect.
Vanin
A F
AF
Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Stukan
R A
RA
Manukhina
E B
EB
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008956:Models, Chemical; D009126:Muscle Relaxation / Q000187:drug effects; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014665:Vasodilator Agents / Q000737:chemistry* / Q000494:pharmacology
D008024:Ligands; D009589:Nitrogen Oxides; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; C073661:dinitrosyl iron complex; D007501:Iron; D013482:Superoxide Dismutase; D005978:Glutathione; D003545:Cysteine