Dinitrosyl Iron Complexes Research Articles

Hypotensive Effect and Accumulation of Dinitrosyl Iron Complexes in Blood and Tissues after Intravenous and Subcutaneous Injection.

Subcutaneous injection of Oxacom with glutathione-bound dinitrosyl iron complex as the active principle produced a slower drop of mean BP and longer accumulation of protein-bound dinitrosyl iron complexes in whole blood and tissues than intravenous injection of this drug, while durations of hypotensive effect in both cases were practically identical. In contrast to intravenous injection of the drug, its subcutaneous administration was not characterized by a high concentration of protein-bound dinitrosyl iron complexes in the blood at the onset of experiment; in addition, accumulation of these NO forms in the lungs was more pronounced after subcutaneous injection than after intravenous one.

New dinitrosyl iron complexes bound with physiologically active dipeptide carnosine.

Dinitrosyl iron complexes (DNICs) are physiological NO derivatives and account for many NO functions in biology. Polyfunctional dipeptide carnosine (beta-alanyl-L-histidine) is considered to be a very promising pharmacological agent. It was shown that in the system containing carnosine, iron ions and Angeli's salt, a new type of DNICs bound with carnosine as ligand {(carnosine)2-Fe-(NO)2}, was formed. We studied how the carbonyl compound methylglyoxal influenced this process. Carnosine-bound DNICs appear to be one of the cell's adaptation mechanisms when the amount of reactive carbonyl compounds increases at hyperglycemia. These complexes can also participate in signal and regulatory ways of NO and can act as protectors at oxidative and carbonyl stress conditions.

250 - Peroxiredoxin 1 Coordination to the Dinitrosyl Iron Complex of Glutathione

Protein S-nitrosation is a reversible post-translational modification that has been associated with a variety of physiological and pathophysiological processes. The mechanisms responsible for S-nitrosation in vivo, however, remain debatable. Dinitrosyl iron complexes (DNIC), which are consistently detected in cell and tissues overproducing nitric oxide, have been proposed as possible S-nitrosating agents in vivo. On the other hand, several reports have described Peroxiredoxins (Prx) S-nitrosation in vivo. Therefore, we became interested in examining whether Prx1 nitrosation was promoted by the mono dinitrosyl iron complex of glutathione ([Fe(NO)2(GS)2]+) equilibrated with its binuclear form ([Fe2(NO)4(GS)2]4+). Apparently, the complex did not promote Prx1 nitrosation. Instead, Prx1 coordinated to the complex producing a high molecular weight complex as attested by EPR experiments at room temperature. An axial EPR signal (g┴=2.03 and g║=2.01) was observed initially, but it became rhombic (gx=2.04; gy=2.03; gz=2.01) with time. Experiments with Prx1 mutants (Prx1C52S, Prx1C83SC173S) and with Prx1 treated with a His modifying reagent showed that Cys52 is responsible for the axial signal and for about 80% of Prx1-DNIC produced, whereas a His residue is responsible for the rhombic signal. The second order rate constant for Prx1-DNIC formation was calculated as k = (6.95±0.42) M-1s-1 at pH 7.4 and 25○C. As anticipated, formation of the Prx1-DNIC complex resulted in the complete inactivation of the peroxidase activity of the enzyme. In addition, SEC experiments demonstrated that Prx1-DNICcomplex shifted the Prx1 dimer-decamer equilibrium to the dimeric state. Reaction of Prx1-DNIC with GSTP1-1, which has been previously shown to bind rapidly and avidly to DNIC, resulted in Prx1 displacement from the complex. In contrast, BSA-DNIC and Prx1-DNIC equilibrated. These results and the reported stability of the DNIC-GSTP1-1 complex argue against the possibility of cellular DNIC complexes acting as nitrosating agents.

Synthesis, X-ray Structures, Electronic Properties, and O2/NO Reactivities of Thiol Dioxygenase Active-Site Models.

Mononuclear non-heme iron complexes that serve as structural and functional mimics of the thiol dioxygenases (TDOs), cysteine dioxygenase (CDO) and cysteamine dioxygenase (ADO), have been prepared and characterized with crystallographic, spectroscopic, kinetic, and computational methods. The high-spin Fe(II) complexes feature the facially coordinating tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP) ligand that replicates the three histidine (3His) triad of the TDO active sites. Further coordination with bidentate l-cysteine ethyl ester (CysOEt) or cysteamine (CysAm) anions yielded five-coordinate (5C) complexes that resemble the substrate-bound forms of CDO and ADO, respectively. Detailed electronic-structure descriptions of the [Fe(Ph2TIP)(LS,N)]BPh4 complexes, where LS,N = CysOEt (1) or CysAm (2), were generated through a combination of spectroscopic techniques [electronic absorption, magnetic circular dichroism (MCD)] and density functional theory (DFT). Complexes 1 and 2 decompose in the presence of O2 to yield the corresponding sulfinic acid (RSO2H) products, thereby emulating the reactivity of the TDO enzymes and related complexes. Rate constants and activation parameters for the dioxygenation reactions were measured and interpreted with the aid of DFT calculations for O2-bound intermediates. Treatment of the TDO models with nitric oxide (NO)-a well-established surrogate of O2-led to a mixture of high-spin and low-spin {FeNO}7 species at low temperature (-70 °C), as indicated by electron paramagnetic resonance (EPR) spectroscopy. At room temperature, these Fe/NO adducts convert to a common species with EPR and infrared (IR) features typical of cationic dinitrosyl iron complexes (DNICs). To complement these results, parallel spectroscopic, computational, and O2/NO reactivity studies were carried out using previously reported TDO models that feature an anionic hydrotris(3-phenyl-5-methyl-pyrazolyl)borate (Ph,MeTp-) ligand. Though the O2 reactivities of the Ph2TIP- and Ph,MeTp-based complexes are quite similar, the supporting ligand perturbs the energies of Fe 3d-based molecular orbitals and modulates Fe-S bond covalency, suggesting possible rationales for the presence of neutral 3His coordination in CDO and ADO.

The binuclear form of dinitrosyl iron complexes with thiol-containing ligands in animal tissues

It has been established that treatment of mice with sodium nitrite, S-nitrosoglutathione and the water-soluble nitroglycerine derivative isosorbide dinitrate (ISDN) as NO donors initiates in vivo synthesis of significant amounts of EPR-silent binuclear dinitrosyl iron complexes (B-DNIC) with thiol-containing ligands in the liver and other tissues of experimental mice. This effect is especially apparent if NO donors are administered to mice simultaneously with the Fe2+-citrate complex. Similar results were obtained in experiments on isolated liver and other mouse tissues treated with gaseous NО in vitro and during stimulation of endogenous NO synthesis in the presence of inducible NO synthase. B-DNIC appeared in mouse tissues after in vitro treatment of tissue samples with an aqueous solution of diethyldithiocarbamate (DETC), which resulted in the transfer of iron-mononitrosyl fragments from B-DNIC to the thiocarbonyl group of DETC and the formation of EPR-detectable mononitrosyl iron complexes (MNIC) with DETC. EPR-Active MNIC with N-methyl-d-glucamine dithiocarbamate (MGD) were synthesized in a similar way. MNIC-MGD were also formed in the reaction of water-soluble MGD-Fe2+ complexes with sodium nitrite, S-nitrosoglutathione and ISDN.

Water-Soluble Dinitrosyl Iron Complex (DNIC): a Nitric Oxide Vehicle Triggering Cancer Cell Death via Apoptosis.

Nitric oxide (NO) is an important cellular signaling molecule that modulates various physiological activities. Angiogenesis-promoting activities of NO-donor drugs have been explored in both experimental and clinical studies. In this study, a structurally well characterized and water-soluble neutral {Fe(NO)2}(9) DNIC [(S(CH2)2OH)(S(CH2)2NH3)Fe(NO)2] (DNIC 2) was synthesized to serve as a NO-donor species. The antitumor activity of DNIC 2 was determined by MTT assay, confocal imaging, and Annexin-V/PI staining. The IC50 values of DNIC 2 were 18.8, 42.9, and 38.6 μM for PC-3, SKBR-3, and CRL5866 tumor cells, respectively. Moreover, DNIC 2 promoted apoptotic cell death via activation of apoptosis-associated proteins and inhibition of survival associated proteins. In particular, DNIC 2 treatment suppressed PC-3 tumor growth by 2.34- and 19.3-fold at 7 and 21 days, in comparison with the control group. These results indicate that water-soluble DNIC 2 may serve as a promising drug for cancer therapy.

Dinitrosyl Iron Complexes and other Physiological Metabolites of Nitric Oxide: Multifarious Role in Plants

This review considers dinitrosyl iron complexes (DNICs) and some other metabolites of nitric oxide (NO) in plants. Nitric oxide is vital for all living organisms, although its role in plants has been studied insufficiently compared with that in animals. We presume that the spectrum of its functions in plants is even wider than in animals. The main NO metabolites could be S-nitrosothiols, DNICs and peroxynitrite. Of particular interest are pro- and antioxidant properties of these compounds. DNICs function and their potential biosynthetic role in plants are practically unknown and brought to the limelight in this review. Since the process of NO biosynthesis in plants is still under discussion, we also specially examine this problem.

Unusual Synthetic Pathway for an {Fe(NO)2}(9) Dinitrosyl Iron Complex (DNIC) and Insight into DNIC Electronic Structure via Nuclear Resonance Vibrational Spectroscopy.

Dinitrosyl iron complexes (DNICs) are among the most abundant NO-derived cellular species. Monomeric DNICs can exist in the {Fe(NO)2}(9) or {Fe(NO)2}(10) oxidation state (in the Enemark-Feltham notation). However, experimental studies of analogous DNICs in both oxidation states are rare, which prevents a thorough understanding of the differences in the electronic structures of these species. Here, the {Fe(NO)2}(9) DNIC [Fe(dmp)(NO)2](OTf) (1; dmp = 2,9-dimethyl-1,10-phenanthroline) is synthesized from a ferrous precursor via an unusual pathway, involving disproportionation of an {FeNO}(7) complex to yield the {Fe(NO)2}(9) DNIC and a ferric species, which is subsequently reduced by NO gas to generate a ferrous complex that re-enters the reaction cycle. In contrast to most {Fe(NO)2}(9) DNICs with neutral N-donor ligands, 1 exhibits high solution stability and can be characterized structurally and spectroscopically. Reduction of 1 yields the corresponding {Fe(NO)2}(10) DNIC [Fe(dmp)(NO)2] (2). The Mössbauer isomer shift of 2 is 0.08 mm/s smaller than that of 1, which indicates that the iron center is slightly more oxidized in the reduced complex. The nuclear resonance vibrational spectra (NRVS) of 1 and 2 are distinct and provide direct experimental insight into differences in bonding in these complexes. In particular, the symmetric out-of-plane Fe-N-O bending mode is shifted to higher energy by 188 cm(-1) in 2 in comparison to 1. Using quantum chemistry centered normal coordinate analysis (QCC-NCA), this is shown to arise from an increase in Fe-NO bond order and a stiffening of the Fe(NO)2 unit upon reduction of 1 to 2. DFT calculations demonstrate that the changes in bonding arise from an iron-centered reduction which leads to a distinct increase in Fe-NO π-back-bonding in {Fe(NO)2}(10) DNICs in comparison to the corresponding {Fe(NO)2}(9) complexes, in agreement with all experimental findings. Finally, the implications of the electronic structure of DNICs for their reactivity are discussed, especially with respect to N-N bond formation in NO reductases.

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso- and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

Nitrite and nitroso compounds can serve as specific catalase inhibitors

Objective: We present evidence that nitrite and nitrosothiols, nitrosoamines and non-heme dinitrosyl iron complexes can reversibly inhibit catalase with equal effectiveness.Methods: Catalase activity was evaluated by the permanganatometric and calorimetric assays.Results: This inhibition is not the result of chemical transformations of these compounds to a single inhibitor, as well as it is not the result of NO release from these substances (as NO traps have no effect on the extent of inhibition). It was found that chloride and bromide in concentration above 80 mM and thiocyanate in concentration above 20 μM enhance catalase inhibition by nitrite and the nitroso compounds more than 100 times. The inhibition degree in this case is comparable with that induced by azide.Discussion: We propose that the direct catalase inhibitor is a positively charged NO-group. This group acquires a positive charge in the active center of enzyme by interaction of nitrite or nitroso compounds with some enzyme groups. Halides and thiocyanate protect the NO+ group from hydration and thus increase its inhibition effect. It is probable that a comparatively low chloride concentration in many cells is the main factor to protect catalase from inhibition by nitrite and nitroso compounds.

The generation of superoxide radicals by complex III in heart mitochondria and the antioxidant effect of dinitrosyl iron complexes at different partial pressures of oxygen

The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE-15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (< 5% O2). Dinitrosyl iron complexes with glutathione (the pharmaceutical drug "Oxacom") exerted an antioxidant effect, regardless of the value of the partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug.

Nitric oxide modulation of the crystallogenic properties of a biological fluid

A comparative analysis of the influence of different nitric oxide forms on the character of the dehydration structuring of human serum samples was carried out. The effects of an NO-containing gas flow that was generated by a Plazon device (800 and 80 ppm), an experimental NO generator (20, 50, 75, and 100 ppm), as well as by glutathione-containing dinitrosyl iron complexes (3 mM/L) were investigated using 15 healthy donors. The influence of endogenous sodium on serum crystallization of intact and NO treated blood samples was evaluated. It was found that the effect of NO on the crystallogenic properties of blood serum is directly determined by its concentration and form (free or bound), as well as by the presence of reactive oxygen species in a gas flow. The most pronounced stimulatory effect was observed for the bound NO form, dinitrosyl iron complexes with glutathione ligands. Low NO concentrations modulated the crystallogenic properties of blood serum, while the best stimulatory effect was demonstrated by the gas flow that contained 20 ppm nitric oxide. In contrast, high NO concentrations (800 ppm) inhibited the crystallogenic activity of the biological medium due to an increase in the destruction of structural elements by many times, which lead to the formation of an additional band in the marginal zone of the microscope specimen.

A new member of the cationic dinitrosyl iron complexes family incorporating N-ethylthiourea is effective against human HeLa and MCF-7 tumor cell lines

A new analog of the active site of mononuclear dinitrosyl [1Fe–2S] proteins, [C3N2H8SFe(NO)2Cl][Fe(NO)2(C3N2H8S)2]+Cl− (I), has been synthesized by reacting NO with an aqueous mixture of iron(II) sulfate and N-ethylthiourea in acidic medium. The structure and properties of the complex were studied by X-ray diffraction, IR, Mössbauer, and EPR spectroscopy, in addition to quantum chemical calculations. Complex I spontaneously generates NO in protic media. The cytotoxicity of I was investigated against human cervical carcinoma (HeLa), breast cancer (MCF7), and non-immortalized (FetMCS) cell lines. The cytotoxicity of I against HeLa is similar to that of anticancer agents currently used clinically (platinum complexes), but I is 10 times less toxic in normal cells. The cytotoxicity of MCF7 cells to I is low.

Effects of NO Donors and Inhibitors of NO Synthase and Guanylate Cyclase on the Acquisition of a Conditioned Defense Food Aversion Response in Edible Snails.

Experiments on edible snails revealed that NO synthase blockade with a nonspecific neuronal NO synthase inhibitor L-NAME before defense food aversion conditioning is followed by a decrease in the rate of learning. Exogenous NO donors, sodium nitroprusside and dinitrosyl iron complex, were shown to improve learning. Chronic administration of a specific soluble guanylate cyclase inhibitor ODQ also increased the rate of learning. Our results indicate that NO has a modulatory effect on the formation of a conditioned response in this type of learning.

Dinitrosyl Iron Complexes with Persulfide Ligands: EPR and Optical Studies

Using the electron paramagnetic resonance (EPR) method, it was established that under aerobic conditions thiol (RS−) groups of thiol-containing ligands within the composition of paramagnetic mononuclear dinitrosyl iron complexes (M-DNIC) are converted into persulfide (RSS−) ligands in the presence of Na2S in water-ethanolic solutions thereby initiating the formation of paramagnetic M-DNIC with persulfide ligands. Correspondingly, the EPR signal of M-DNIC with thiol-containing ligands at g ⊥ = 2.04, g ∥ = 2.014, and g aver. = 2.031 is substituted for the EPR signal characteristic of M-DNIC with persulfide ligands at g ⊥ = 2.04, g ∥ = 2.02, and g aver. = 2.033. With the increase in the registration temperature to ambient temperature, the anisotropic shape of the EPR signal of M-DNIC with persulfide ligands recorded at 77 K and determined by the anisotropy of the g-factor turns into the symmetric shape with a halfwidth of 0.3–0.4 mT. The lack of the five-component hyperfine structure (HFS) of this EPR signal caused by the interaction of the unpaired electron with the nitrogen nuclei of two nitrosyl ligands is attributed to the compensation of the differently charged contributions of isotropic HFS formed as a result of the spin polarization of appropriate molecular orbitals. It is suggested that similar to M-DNIC with thiol-containing ligands, M-DNIC with persulfide ligands are characterized by the d 7 electronic configuration of the iron atom and the localization of the unpaired electron on MO(dz2). The incorporation of 57Fe into M-DNIC with persulfide ligands is accompanied by doublet HFS splitting of the EPR signal of M-DNIC by virtue of the mononuclear nature of the latter. It is concluded that M-DNIC with persulfide ligands may exist in the form of both low-molecular and protein-bound complexes and have relevance to the recently established biological activity of hydrogen sulfide and its derivatives.

Mechanism of inhibition of NiFe hydrogenase by nitric oxide

Hydrogenases reversibly catalyze the oxidation of molecular hydrogen and are inhibited by several small molecules including O2, CO and NO. In the present work, we investigate the mechanism of inhibition by NO of the oxygen-sensitive NiFe hydrogenase from Desulfovibrio fructosovorans by coupling site-directed mutagenesis, protein film voltammetry (PFV) and EPR spectroscopy. We show that micromolar NO strongly inhibits NiFe hydrogenase and that the mechanism of inhibition is complex, with NO targeting several metallic sites in the protein. NO reacts readily at the NiFe active site according to a two-step mechanism. The first and faster step is the reversible binding of NO to the active site followed by a slower and irreversible transformation at the active site. NO also induces irreversible damage of the iron–sulfur centers chain. We give direct evidence of preferential nitrosylation of the medial [3Fe–4S] to form dinitrosyl–iron complexes.

Phosphine-ligated dinitrosyl iron complexes for redox-controlled NO release.

Here we present the syntheses and structural, spectroscopic, as well as electrochemical properties of four dinitrosyl iron complexes (DNICs) based on silicon- and carbon-derived di- and tripodal phosphines. Whereas CH3C(CH2PPh2)3 and Ph2Si(CH2PPh2)2 coordinate iron in a η(2) - binding mode, CH3Si(CH2PPh2)3 undergoes cleavage of one Si-C bond to afford [Fe(NO)2(P(CH3)Ph2)2] at elevated temperatures. The complexes were characterized by IR spectroelectrochemistry as well as UV-vis measurements. The oxidized {Fe(NO)2}(9) compounds were obtained by oxidation with (NH4)2[Ce(NO3)6] and their properties evaluated with Mössbauer and IR spectroscopy. Stability experiments on the complexes suggest that they are capable of releasing their NO-ligands in the oxidized {Fe(NO)2}(9) but not in the reduced {Fe(NO)2}(10) form. A detailed DFT analysis is provided in order to understand the electronic configurations and the complexes' ability to release NO.

Vitamin Para-Aminobenzoic Acid (PABA) Controls Generation of Nitric Oxide (NO) In Vitro and its Biological Functions in the Bacterial Cells

Nitric oxide (NO) serves either a universal signaling molecule or extremely toxic agent, depending on the dose. Up to date there have been a very limited number of natural compounds serving as effective regulators of NO signaling and toxic potencies. NO acts in concert with H2S to coordinate cell responses; however, how exactly this interaction is achieved is not known. Both agents have an effect on the accumulation of both reactive chemical species, ROS and RNS and can give rise to other reactive species. Para-aminobenzoic acid (PABA) is an essential metabolite for certain organisms. Once considered a vitamin, PABA, functions as an effective inhibitor of inducible SOS DNA repair processes in E. coli. In the present study we focus on the genetic and physiological evidence in favor of interference of NO-donors and PABA in bacterial cells with DNA repair gene expression and biofilm formation, depending on the rate of NOdonating in vitro and intracellular ROS/RNS accumulation in the cells. The crystalline dinitrosyl iron complexes (NO- 29 and NO-33) with thiourea as the ligands and 3 crystalline tetranitrosyl iron complexes with thiosulfate (TNICthio) - and with sulfur-containing aliphatic ligands – cysteamine and penicillamine were studied first as the NO-donors in pure solutions and in the combination with PABA. In E. coli cells with the combined action of PABA (0.01-5 mM) with nitric oxide donors we observed an inhibition of NO-signaling potency in the SOS (sfiA gene)- and the SoxRS (soxS gene) DNA repair pathway up to 3.5 fold, depending on the dose of PABA. PABA tested at 0.5 mM afforded 24% protection against the level of biofilm formation induced by TNICthio. Using the antioxidant-capacity assay, we observed a many-fold decrease in the ROS/RNS level production in the samples of E. coli cells with PABA and NO-donor-TNICthio.

The antitumor activity of the S-nitrosoglutathione and dinitrosyl iron complex with glutathione: Comparative studies

The antitumor activity of the binuclear form of dinitrosyl iron complexes with glutathione against Lewis lung carcinoma was found earlier with intraperitoneal administration of the complexes. This activity was also observed when this preparation was injected subcutaneously. The complex inhibited the tumor growth by 43% upon subcutaneous injection at a daily dose of 100 µM/kg (as calculated per one iron atom in the binuclear dinitrosyl iron complex) for 10 or 15 days. The effect was observed during the first 2 weeks after tumor transplantation. After this, the tumors began to grow at a rate that was equal to or even higher than that for the control animals. The mean survival time for the treated mice exceeded the control values by 30%. Binuclear dinitrosyl iron complexes were also effective against Ca-755 adenocarcinoma with intraperitoneal administration. In this case, however, the mean survival time for the treated animals only increased by 7%. It was also shown that S-nitrosoglutathione inhibited the growth of Lewis lung carcinoma and Ca-755 adenocarcinoma by 70 and 90%, respectively. However, in contrast to binuclear dinitrosyl iron complexes, the antitumor effect of S-nitrosoglutathione decreased with an increase in the daily dose of the compound from 200 to 400 µM/kg. The initial antitumor effect of binuclear dinitrosyl iron complexes and S-nitrosoglutathione is suggested to be due to NO that is released from both compounds. The subsequent suppression of the effect is caused by the activation of antinitrosative and antioxidant defense systems in tumors.

Synthesis and structure of new dinitrosyl iron complexes with bridging thiolate ligands [Fe2(μ-SR)2(NO)4

Two new dinitrosyl iron complexes with bridging thiolate ligands [Fe2(µ-SR)2(NO)4], where R = n-Hex or cyclo-Hex, were synthesized and their molecular structures were analyzed. The structure of the [Fe2(µ-S-n-Hex)2(NO)4] complex was determined by X-ray diffraction. For the [Fe2(µ-S-cyclo-Hex)2(NO)4] complex, the geometry was assigned based on the results of structure-sensitive spectroscopic methods and DFT quantum chemical calculations.