Redox Reactions and Stability of Dinitrosyl Iron Complexes with Thiolate Ligands as Potential Donors and Carriers of Nitric Oxide

I. I. Lobysheva,^1,2 V. A. Serezhenkov,¹ R. A. Stucan,¹ M. K. Bowman,³ and A. F. Vanin¹

¹Institute of Chemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977 Russia; fax: (095) 938-21-56.

²To whom correspondence should be addressed.

³Environmental Molecular Sciences Laboratory, PNNL, Richland, WA, USA.

Submitted March 18, 1997; revision submitted April 8, 1997.

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The effect of free thiols on the redox properties and stability of monomeric and dimeric forms of dinitrosyl iron complexes (DNIC) with cysteine and glutathione under aerobic and anaerobic conditions has been studied. DNIC containing cysteine and glutathione are dimeric in solutions at low concentration of free thiols and monomeric when the iron/thiol ratio is lower than 1:20. Dimerization has been shown to affect redox properties of DNIC. Optical spectra of dimeric and monomeric forms undergo similar changes after DNIC reduction with sodium dithionite. Absorption maxima at 310 and 360 nm characteristic for dimeric forms of DNIC disappear and two bands at 460 and 660 nm are observed. Formation of a new band at 570 nm following the disappearance of these bands in dimeric forms is characterized with k = (3.4 ± 0.5)·10^-3 sec^-1. The formation of this complex is not revealed for monomers. The stability of the initial and reduced complexes has been studied by EPR and Mossbauer spectroscopy. It is shown to be determined essentially by anionic ligands. Reduction of the complex does not affect its stability under aerobic conditions. The intermediate complexes formed under aerobic conditions at low concentrations of sodium dithionite are less stable, however a reduced dimeric form characterized by an absorption band at 570 nm is as stable as the initial form. The study revealed that DNIC stability in the body is strongly dependent on the concentration of free thiol groups, the redox potential of the environment, and oxygen concentration. Thus it can regulate release and accumulation of nitric oxide in tissues.

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KEY WORDS: glutathione, nitric oxide, EPR of iron complexes, redox properties of nitrosyl products.

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