Tatyana E. Shubina

Chemical characterization of the smallest S-nitrosothiol, HSNO; cellular cross-talk of H2S and S-nitrosothiols.

Dihydrogen sulfide recently emerged as a biological signaling molecule with important physiological roles and significant pharmacological potential. Chemically plausible explanations for its mechanisms of action have remained elusive, however. Here, we report that H2S reacts with S-nitrosothiols to form thionitrous acid (HSNO), the smallest S-nitrosothiol. These results demonstrate that, at the cellular level, HSNO can be metabolized to afford NO+, NO, and NO– species, all of which have distinct physiological consequences of their own. We further show that HSNO can freely diffuse through membranes, facilitating transnitrosation of proteins such as hemoglobin. The data presented in this study explain some of the physiological effects ascribed to H2S, but, more broadly, introduce a new signaling molecule, HSNO, and suggest that it may play a key role in cellular redox regulation.

Quantum-chemical calculations of CO and OH interacting with bimetallic surfaces

In this work we present results of a periodic density-functional theory study of the adsorption of carbon monoxide (CO) and hydroxyl (OH) on platinum–ruthenium, platinum–molybdenum and platinum–tin alloys as well as the adsorption of CO on a series of transition metals modified with a Pt overlayer. The surfaces are modelled as four-layer slabs (three-layer slab in case of Pt3Sn(111)). The binding energies and geometries of CO and OH are computed. In the case of PtRu, the mixing of Pt by Ru leads to a weaker bond of both CO and OH to the Pt sites, whereas mixing of Ru by Pt causes a stronger bond of CO and OH to the Ru sites. The binding energy trends for CO do not show a clear-cut relationship with its vibrational characteristics. The mixing of Pt by Mo leads to weakly adsorbed CO on both Pt and Mo sites, and OH strongly adsorbed only on Mo sites. This suggests that PtMo could be a better bifunctional catalyst for CO oxidation then PtRu. On Pt3Sn(111) the calculations show that CO binds only to Pt and not to the Sn, whereas OH has an energetic preference for the Sn sites. This also implies that PtSn should be a good CO oxidation catalyst. For Pt–monolayer systems, we demonstrate a relationship between the PtPt distance in the monolayer and the changes in the CO binding energy. The nature of the substrate seems to be of secondary importance.

Coordination and Metalation Bifunctionality of Cu with 5,10,15,20-Tetra(4-pyridyl)porphyrin: Toward a Mixed-Valence Two-Dimensional Coordination Network

We investigated the coordination self-assembly and metalation reaction of Cu with 5,10,15,20-tetra(4-pyridyl)porphyrin (2HTPyP) on a Au(111) surface by means of scanning tunneling microscopy, X-ray photoelectron spectroscopy, and density functional theory calculations. 2HTPyP was found to interact with Cu through both the peripheral pyridyl groups and the porphyrin core. Pairs of pyridyl groups from neighboring molecules coordinate Cu(0) atoms, which leads to the formation of a supramolecular metal-organic coordination network. The network formation occurs at room temperature; annealing at 450 K enhances the process. The interaction of Cu with the porphyrin core is more complex. At room temperature, formation of an initial complex Cu(0)-2HTPyP is observed. Annealing at 450 K activates an intramolecular redox reaction, by which the coordinated Cu(0) is oxidized to Cu(II) and the complex Cu(II)TPyP is formed. The coordination network consists then of Cu(II) complexes linked by Cu(0) atoms; that is, it represents a mixed-valence two-dimensional coordination network consisting of an ordered array of Cu(II) and Cu(0) centers. Above 520 K, the network degrades and the Cu atoms in the linking positions diffuse into the substrate, while the Cu(II)TPyP complexes form a close-packed structure that is stabilized by weak intermolecular interactions. Density functional theory investigations show that the reaction with Cu(0) proceeds via formation of an initial complex between metal atom and porphyrin followed by formation of Cu(II) porphyrin within the course of the reaction. The activation barrier of the rate limiting step was found to be 24-37 kcal mol(-1) depending on the method used. In addition, linear coordination of a Cu atom by two CuTPyP molecules is favorable according to gas-phase calculations.

Ab initio calculations of intermediates of oxygen reduction on low-index platinum surfaces

Properties of the oxygen molecule, atomic oxygen, and intermediate products of its reduction, OH, OOH, H 2 O 2 on (111), (100), and (110) Pt surfaces have been investigated using periodic density functional theory. The Pt surfaces are modeled as four-layer slabs. Adsorption energies and geometries, as well as the charge-transfer properties are calculated. Computed characteristics of the adsorbed oxygen reduction intermediates supply known tendencies of the low index Pt surface activities under different experimental conditions. Electric field dependencies of the properties of all species adsorbed on a Pt 9 (111) cluster have been also studied. Lowering the field causes an increase of the O-O bond length of O 2ads , attracting the molecule to the Pt surface and increasing the charge transfer from Pt to 2π* orbitals of the oxygen molecule. The weakening of the O-O bond is evidenced by a decrease of the O-O stretching frequency. The charge-transfer from the Pt 9 cluster to the adsorbates is observed for all species. In our calculations hydrogen peroxide was unstable on all three low-index Pt surfaces and dissociated into two hydroxyls or a water molecule and atomic oxygen. The results of the calculations are discussed in the context of the mechanism of oxygen reduction.

Biochemical insight into physiological effects of H2S: reaction with peroxynitrite and formation of a new nitric oxide donor, sulfinyl nitrite

The reaction of hydrogen sulfide (H2S) with peroxynitrite (a key mediator in numerous pathological states) was studied in vitro and in different cellular models. The results show that H2S can scavenge peroxynitrite with a corresponding second order rate constant of 3.3 ± 0.4 × 10³ M⁻¹·s⁻¹ at 23°C (8 ± 2 × 10³ M⁻¹·s⁻¹ at 37°C). Activation parameters for the reaction (ΔH‡, ΔS‡ and ΔV‡) revealed that the mechanism is rather associative than multi-step free-radical as expected for other thiols. This is in agreement with a primary formation of a new reaction product characterized by spectral and computational studies as HSNO₂ (thionitrate), predominantly present as sulfinyl nitrite, HS(O)NO. This is the first time a thionitrate has been shown to be generated under biologically relevant conditions. The potential of HS(O)NO to serve as a NO donor in a pH-dependent manner and its ability to release NO inside the cells has been demonstrated. Thus sulfide modulates the chemistry and biological effects of peroxynitrite by its scavenging and formation of a new chemical entity (HSNO₂) with the potential to release NO, suppressing the pro-apoptotic, oxidative and nitrative properties of peroxynitrite. Physiological concentrations of H₂S abrogated peroxynitrite-induced cell damage as demonstrated by the: (i) inhibition of apoptosis and necrosis caused by peroxynitrite; (ii) prevention of protein nitration; and (iii) inhibition of PARP-1 [poly(ADP-ribose) polymerase 1] activation in cellular models, implying that a major part of the cytoprotective effects of hydrogen sulfide may be mediated by modulation of peroxynitrite chemistry, in particular under inflammatory conditions.

Does perthionitrite (SSNO(-)) account for sustained bioactivity of NO? A (bio)chemical characterization.

Hydrogen sulfide (H2S) and nitric oxide (NO) are important signaling molecules that regulate several physiological functions. Understanding the chemistry behind their interplay is important for explaining these functions. The reaction of H2S with S-nitrosothiols to form the smallest S-nitrosothiol, thionitrous acid (HSNO), is one example of physiologically relevant cross-talk between H2S and nitrogen species. Perthionitrite (SSNO(-)) has recently been considered as an important biological source of NO that is far more stable and longer living than HSNO. In order to experimentally address this issue here, we prepared SSNO(-) by two different approaches, which lead to two distinct species: SSNO(-) and dithionitric acid [HON(S)S/HSN(O)S]. (H)S2NO species and their reactivity were studied by (15)N NMR, IR, electron paramagnetic resonance and high-resolution electrospray ionization time-of-flight mass spectrometry, as well as by X-ray structure analysis and cyclic voltammetry. The obtained results pointed toward the inherent instability of SSNO(-) in water solutions. SSNO(-) decomposed readily in the presence of light, water, or acid, with concomitant formation of elemental sulfur and HNO. Furthermore, SSNO(-) reacted with H2S to generate HSNO. Computational studies on (H)SSNO provided additional explanations for its instability. Thus, on the basis of our data, it seems to be less probable that SSNO(-) can serve as a signaling molecule and biological source of NO. SSNO(-) salts could, however, be used as fast generators of HNO in water solutions.

Water exchange on manganese(III) porphyrins. Mechanistic insights relevant for oxygen evolving complex and superoxide dismutation catalysis.

In this work the rate constants (k(ex)) and the activation parameters (DeltaH(double dagger), DeltaS(double dagger), and DeltaV(double dagger)) for the water exchange process on Mn(III) centers have experimentally been determined using temperature and pressure dependent (17)O NMR techniques. For the investigations the Mn(III) porphyrin complexes [Mn(III)(TPPS)S(2)](n-) and [Mn(III)(TMpyP)S(2)](n+) (S = H(2)O and/or OH(-)) have been selected due to their high solution stability in a wide pH range, enabling the measurements of water exchange in the case of both diaqua and aqua-hydroxo complexes. We have experimentally demonstrated that the water exchange on Mn(III) porphyrins is a fast process (k(ex) approximately = 10(7) s(-1)) of an I(d) to I mechanism, strongly influenced by a Jahn-Teller effect and as such almost independent of a porphyrin charge and a trans ligand. This is also supported by our DFT calculations which show only a slight difference in an average Mn(III)-OH(2) bond found for a positively charged model porphyrin with protonated pyridine groups (2.446 A) and for a simple model without any substituents on the porphyrin ring (2.437 A). The calculated effective charge on the Mn center, which is significantly lower than its formal +3 charge (ca. +1.5 for diaqua; +1.4 for aqua-hydroxo), also contributes to its substitution lability. The herein presented results are discussed in connection to a possible fast exchanging substrate binding site in photosystem II and corresponding inorganic model complexes, as well as in the context of a possible inner-sphere catalytic pathway for superoxide dismutation on Mn centers.

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

Summary A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene. Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism.

Conformationally restricted GABA analogs: from rigid carbocycles to cage hydrocarbons

GABA was discovered to play an important role as the major inhibitory neurotransmitter in the adult mammalian CNS 60 years ago. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. In an effort to increase the lipophilicity and to reduce conformational flexibility of GABA itself, a polycyclic or cage hydrocarbon framework can be introduced into the 3D structure of GABA in order to better control the binding. This article explores the available synthetic methods, properties and activity of carbocyclic (cyclopropanes, cyclobutanes and cyclohexanes) and cage (adamantane and others) hydrocarbons - analogs of GABA with conformationally rigid carbon skeletons.

Anticorrosive properties of N-acetylmethylpyridinium bromides

The inhibiting action of N-acetylmethylpyridinium bromides on the corrosion of low-carbon steel in a 3 M sulfuric acid solution at 20, 40, 60, and 80°C was studied. The mechanism of their protective action was examined using electrochemical methods. Compounds exhibiting high anticorrosive properties at elevated temperatures were found.