N. A. Sanina

Functional models of [Fe—S] nitrosyl proteins

The review surveys methods for the synthesis, as well as structures and properties of sulfur-containing iron nitrosyl complexes serving as models of active sites of [Fe—S] nitrosyl proteins, which are potential donors of nitrogen monoxide.

Synthesis and X-ray and Spectral Study of the Compounds [Q4N]2[Fe2(S2O3)2(NO)4] (Q = Me, Et, n-Pr, n-Bu)

Iron nitrosyl complexes with general formula [Q4N]2[Fe2(S2O3)2(NO)4] (Q = Me, Et, n-Pr, n-Bu) were synthesized by the exchange reaction of K2[Fe2(S2O3)2(NO)4] with tetraalkylammonium bromides. The molecular and crystal structure of [(CH3)4N]2[Fe2(S2O3)2(NO)4] were studied by X-ray diffraction analysis. The iron atom in the four-membered cycle of the [2Fe–2S] anion is bound to another Fe atom and to two sulfur atoms and is coordinated by two nonequivalent NO groups, each bridging sulfur atom being bound to the SO3group. The structurally equivalent iron atoms are in the state Fe1–(S= 1/2). The Mössbauer spectroscopy method shows that the complexes are diamagnetic due to the strong Fe–Fe bond. It is found that the SO3group provides higher stability of the thiosulfate anion than the anion in Roussins red salt [Fe2S2(NO)4]2–.

[Fe2(μ-SC5H4N)2(NO)4] as a New Potential NO Donor: Synthesis, Structure, and Properties

A new potential donor of nitrogen monoxide, a binuclear iron sulfur nitroso complex, was prepared by exchange reaction of Na2Fe2(S2O3)2(NO)4 with pyridine-2-thiol in the presence of sodium thiosulfate at pH 12. The molecular and crystal structures of [Fe2(μ-SC5H4N)2(NO)4] were studied by X-ray diffraction analysis. The type of iron coordination by pyridine-2-thiol in the presence of a coordinated NO molecule was determined. In vacuum, the structure of the complex is destroyed, which is accompanied by NO evolution, while exposure to UV radiation results in decomposition of the complex and in a release of N2O.

The structures of the dicationic tetranitrosyl iron complex with cysteamine [Fe2S2(CH2CH2NH3)2(NO)4]2+ and its decomposition products in protic media: an experimental and theoretical study

Decomposition products of [Fe2S2(CH2CH2NH3)2(NO)4]SO4·2.5H2O (1′) were studied by electrochemistry and mass spectrometry. The structures of the dicationic tetranitrosyl iron complex with cysteamine of the composition [Fe2S2(CH2CH2NH3)2(NO)4]2+ (1) and possible products of its decomposition and NO replacement by an aqua ligand were studied by quantum chemical methods at the density functional theory level. Taking into account the solvation effects, the replacement of the nitrosyl ligand in dication 1 by an aqua ligand was found to be less favorable in aqueous solution than in the gas phase. The pK value was calculated for the proton abstraction from the NH3 group of compound 1 (7.2), and the removal of NO from the deprotonated form of the complex was found to be much easier. This result is consistent with the experimental data on an increase in the rate of NO formation in aqueous solutions of 1 with increasing pH from 6 to 8 assuming that the increase in pH is accompanied by an increase in the percentage of the less stable deprotonated form of the complex and that OH− does not participate in the elementary step of NO formation. The kinetic curves of NO formation are well described by a two-step scheme of consecutive first-order reactions of the NO formation and consumption. In the gas phase, dication 1 was found to be unstable to decomposition into two mononuclear cationic dinitrosyl iron complexes with cysteamine. This result is consistent with the fact that these cations are observed in the electrospray ionization mass spectrometric experiment. The major peak in the mass spectra is associated with the [Fe2S2(CH2CH2NH3)2(NO)4 − H]+ ion. As follows from the calculations, this is due to the deprotonation of the dication as it gets rid of the hydration shell, because even the dimer of water molecules is more basic than dication 1.

Synthesis, structure, NO donor activity of iron–sulfur nitrosyl complex with 2-aminophenol-2-yl and its antiproliferative activity against human cancer cells

A new tetranitrosyl binuclear iron complex, [Fe2(SC6H6N)2(NO)4] (1), has been synthesized by two methods. Molecular and crystalline structure of 1 were determined by X-ray analysis; the complex is binuclear of “μ-S” type with ~2.7052(4) Å between the irons. The compound crystallizes in monoclinic, space group P21/n, Z = 2; parameters of the unit cell: a = 6.6257(2) Å, b = 7.9337(2) Å, c = 16.7858(4) Å, β = 96.742(2)°, V = 876.26(4) Å3. Parameters of Mössbauer spectrum for 1 are: isomer shift δFe = 0.096(1) mm/s, quadrupole splitting ΔEQ = 1.122(1) mm/s, line width 0.264(1) mm/s at 293 K. As follows from the electrochemical analysis of aqueous solutions of 1, it generates NO in protonic media without additional activation. NO amount and the rate of its activation are much higher in acidic solutions than in neutral and alkali ones. The constants of hydrolytic decomposition of 1 were calculated. The geometry and electronic structure of isolated 1 were studied using the density functional theory. Differential sensitivity of four lines of human tumor cells of various genesis to 1 has been determined (ovarian carcinoma (SCOV3), large intestine cancer (LS174T), mammary gland carcinoma (MCF7), and non-small cell carcinoma of lung (A549)); dependence of tumor cells amount on the complex concentration has been studied in order to use the complex as a promising antitumor agent for trials in vivo.

Influence of aromatic ligand on the redox activity of neutral binuclear tetranitrosyl iron complexes [Fe2(μ-SR)2(NO)4]: experiments and quantum-chemical modeling

Reduction of neutral binuclear nitrosyl iron complexes of “μ-S” structural type [Fe2(SR)2(NO)4] with R = 3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, 5-nitropyridine-2-yl and pyridine-2-yl in aprotic solution has been studied by a cyclic voltammetry (CVA) method at a wide range of potential scan rates. A complex with R = 3-nitro-phenol-2-yl was synthesized for the first time; therefore it was studied by X-ray and Mossbauer spectroscopy. The parameters of the Mossbauer spectrum are: isomer shift δFe = 0.115(1) mm s−1, quadrupole splitting ΔEQ = 1.171(1) mm s−1, and line width = 0.241(1) mm s−1 at 85 K. From the current–voltage curve, the transfer of the first electron was found to be reversible, and the redox-potentials of these reactions were determined. The further reduction of the complexes was determined to be irreversible because the product of the second electron addition is instable and decomposes partially during the potential scan. Calculations of geometric and electronic structures of monoanions and dianions of the complexes under study and their theoretical redox-potentials were performed by DFT methods. Introduction of the electron-acceptor NO2 group into the phenyl and pyridine rings of sulfur-containing ligands of the nitrosyl iron complexes was found to affect the geometry of the anions and the distribution of the additional negative charge, as well as to increase the redox-potential and to facilitate reduction of these complexes.

Structures of bis(1-methyltetrazole-5-thiolato)(tetranitrosyl)diiron and its intermediates in solutions

Single crystals of an iron complex with 1-methyltetrazole-5-thiol of the formula [Fe2(SC2H3N4)2(NO)4] (I) were obtained and examined by X-ray diffraction. According to electrochemical data, tetranitrosyl binuclear complex I rapidly decomposes in protic solvents with elimination of NO. The maximum amount of NO generated by complex I in 1% aqueous DMSO is ∼900 nmol. This amount is reduced by half 15 min after the beginning of the decomposition under anaerobic conditions. The dinitrosyl mononuclear intermediates [Fe(SC2H3N4)2(NO)]− and [Fe(SC2H3N4)2(NO)2]− were detected in solutions and identified by EPR spectroscopy and mass spectrometry. The low number of spins per complex in solutions indicates that the mononuclear complexes undergo further decomposition into NO and the species [Fe(SC2H3N4)3]−, [SC2H3N4]−, and [Fe4S3(NO)7]−. Complex I was found to be substantially more stable in DMSO than in methanol and 1% aqueous DMSO.

Synthesis, crystal structures, Mössbauer spectra, and redox properties of binuclear and tetranuclear iron-sulfur nitrosyl clusters

The iron-sulfur nitrosyl complexes A[Fe4S3(NO)7], where A=Na+, NH4+, or N(Bun)4+, and B2[Fe2S2(NO)4], where B=Na+, Cs+, or N(Bun)4+, were synthesized. Their structures and properties were studied by X-ray diffraction analysis, Mössbauer spectroscopy, and cyclic voltammetry. The effect of the crystal packing on the geometry of the tetranuclear NH4[Fe4S3(NO)7]·H2O and binuclear Cs2[Fe2S2(NO)4]·2H2O complexes was analyzed. The changes in the Fe57 Mössbauer spectral parameters of the anion in the B2[Fe2S2(NO)4] series depend on the size of the B cation and agree with variations in the structural parameters of the Fe[S2(NO)2] chromophores as well as in the stretching vibrations of the NO groups caused by changes in intermolecular contacts. The presence of electronic states delocalized through the Fe−Fe bonds explains the fact that the electronic states of the Fea(S3NO) and Feb(S2(NO)2) chromophores in the [Fe4S3(NO)7]− anion are nearly identical. The binuclear clusters are unstable upon storage in the solid phase and decompose in solutions to form the tetranuclear [Fe4S3(NO)7]− complexes, sulfur, and nitrogen oxides. The redox properties of the [Fe4S3(NO)7]− and [Fe2S2(NO4)]2− anions in CH3CN and THF solutions were studied. The mechanism of reduction of the anion in the tetranuclear cluster is proposed.

Nitrosyl iron complexes with enhanced NO donating ability: synthesis, structure and properties of a new type of salt with the DNIC cations [Fe(SC(NH2)2)2(NO)2]+

Novel nitrosyl iron complexes [Fe(SC(NH2)2)2(NO)2]2SO4·H2O(I) and [Fe(SC(NH2)2)2(NO)2]2[Fe2(S2O3)2(NO)4](II) have been synthesized via the reactions of FeSO4 and Na2[Fe2(S2O3)2(NO)4], respectively, with acidic solutions of thiocarbamide in water. The structure and properties of I and II were studied using X-ray analysis, Mossbauer, IR, and EPR spectroscopy and amperometry. Both complexes are characterized by a prolonged NO generation without additional activation in aqueous anaerobic solutions, similar to the organic NO donor diethylene triamine; however, they are more effective: at pH 7 the NO amount is ∼32.6 and ∼31.8 nM mol−1 of the complex for I and II, respectively. The obtained results show feasibility for the synthesis of water-soluble hybrid nitrosyl NO-generating complexes, which contain the NO groups both in the cationic and anionic sublattices and provide the control of the NO release kinetics.

[Bu4N]2[Fe2(μ-S2O3)2(NO)4]: Synthesis, Structure, Redox Properties, and EPR Study

The [n-Bu4N]2[Fe2(μ-S2O3)2(NO)4] complex was studied using X-ray diffraction analysis, cyclic voltammetry, and EPR spectroscopy, and its crystal structure was determined. The redox properties of the [Fe2(μ-S2O3)2(NO)4]2–anion in CH3CN and CH2Cl2solutions were studied. An addition of excess reducer (sodium thiosulfate) to the thiosulfate complex was shown to produce an EPR signal with g= 2.03 typical of the mononuclear iron dinitrosyl complexes. The mechanism for [Fe2(μ-S2O3)2(NO)4]2–reduction was suggested.