Dinitrosyl iron complexes with thiolate ligands: Physico-chemistry, biochemistry and physiology

Some present-day concepts on the origin and functional activities of dinitrosyl iron complexes (DNIC) with thiolate ligands are considered. Nitric oxide (NO) including to DNIC increases its stability and ensures effective targeting of NO to organs and tissues. DNIC have a square-planar structure; unpaired electron is localized on the d(z2) orbital of the d(7) iron atom. The formula of DNIC appears as {(RS-)(2)Fe+(NO+)(2)....(-SR)(2)}(-); electron spin is S = 1/2. Conversion of an originally diamagnetic group, Fe2+(NO)(2) with electron configuration d(8), into a paramagnetic Fe+(NO+)(2) group is a result of disproportionation of NO ligands and substitution of newly generated NO- for NO. The nitrosonium ions present in DNIC impart to them high nitrosylating activity, e.g., ability to induce S-nitrosylation of thiols. The ability of S-nitrosothiols to form DNIC in a direct reaction with bivalent iron is a prerequisite to effective mutual conversions of DNIC and S-nitrosothiols. In this work, I consider some mechanisms of destructive effects of low-molecular DNIC on active centers of iron-sulfur proteins, ability of DNIC to express certain genes, to activate guanylate cyclase, to exert hypotensive, vasodilator effects, to inhibit platelet aggregation, to accelerate wound healing and to produce potent erective action. Recently a stabilized powder-like polymeric composition based on dimeric glutathione DNIC the water-soluble polymer in which was used as a filling agent was designed. The advantages of this stable DNIC-glutathione preparation include their ability to retain their physico-chemical and functional activities within at least one year. At present, the preparation undergo testing as a base for the design of a wide variety of broad-spectrum drugs. (C) 2009 Elsevier Inc. All rights reserved.