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The effect of certain NO donors, viz., nitrosyl iron complexes (NICs) and their functional thio ligands, on the activity of hydrolytic enzymes was studied taking cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) and sarcoplasmic reticulum (SR) Ca2+-ATPase as examples. It was shown that mononuclear dinitrosyl complexes with 4-nitrophenyl- and 5-nitropyridin-2-ylthiols as well as the binuclear tetranitrosyl complex with 3-hydroxyphenylthiol competitively inhibit the cGMP PDE action with the inhibition constants, Ki, equal to 2.3 · 10−6, 1.0 · 10−4, and 8.7 · 10−5 mol L−1, respectively, and non-competitively inhibit the function of SR Ca2+-ATPase with Ki = 7.4 · 10−5, 7.9 · 10−5 and 1.1 · 10−5 mol L−1, respectively. The thio ligands of the complexes have little effect on the enzyme activity or do not affect it at all. The results obtained make it possible to predict the antihypertensive, antiaggregatory, and vasodilatory activities of the compounds studied. [ABSTRACT FROM AUTHOR]

High-molecular-weight dinitrosyl iron complexes (DNICs) are formed in living systems and are a stable depot of nitrogen monoxide (NO). In this work, using experimental and theoretical methods, we investigated the interaction of their synthetic analog, a promising cardiotropic complex of the composition [Fe(SC(NH2)2)2(NO)2]2[Fe2(S2O3)2(NO)4], with bovine serum albumin (BSA) in aqueous aerobic solutions. We suggested that, under these conditions, the decomposition product of the initial complex with oxygen, the [Fe(NO)(NO2)]+ fragment, can bind in the hydrophobic pocket of the protein. As a result of this interaction, high-molecular-weight Fe(Cys34)(His39)(NO)(NO2) is formed. The binding constant of the complex with protein measured by the quenching of intrinsic fluorescence of BSA is 7.2 × 105 M−1. According to EPR and UV-spectroscopy data, the interaction of the complex with the protein leads to its significant stabilization. In addition to coordination binding, the studied complex can be adsorbed onto the protein surface due to weak intermolecular interactions, resulting in the prolonged generation of NO. [ABSTRACT FROM AUTHOR]

Interaction and transformation of the mononuclear cationic dinitrosyl iron complex [Fe(SC(NH2)2)2(NO)2]+ (complex 1) upon binding with bovine serum albumin (BSA) have been explored using kinetic measurements, UV-Vis and fluorescence spectroscopy, and computational molecular modeling. BSA was found to bind up to five molecules of complex 1 per one protein molecule; as a result, the rate of NO release by complex 1 into solution decreases by a factor of 10. The binding constant of complex 1 with BSA measured by the quenching of intrinsic fluorescence of BSA is 5 × 105 М−1. Molecular docking calculations at pH = 7 have determined five−six low-energy binding sites for complex 1 at subunits I and II of BSA. The most stable protein−ligand complexes are located at the protein pockets near Cys34. The spectroscopic measurements and docking calculations have shown that the decomposition product of complex 1, the Fe(NO)2+ fragment, can form an adduct Fe(Cys34)(His39)(NO)2 (complex 2) with the coordination bonds of Fe with atoms S of Cys34 and ND of His39. The structure of complex 2 was supported by the density functional calculations of the absorption spectrum. Decomposition of complex 2 leads to nitrosylation of BSA at atom S of Cys34. Complexes 1 (bound with BSA), 2 and the nitrosylated BSA can serve as NO depot in plasma. [ABSTRACT FROM AUTHOR]

The effect of N-nitroxymethyl succinimide (1), N-(2-nitroxyethyl) succinimide (2) and N-(3-nitroxypropyl) succinimide (3) on enzymatic activity of cyclic guanosine monophosphate (cGMP) phosphodiesterase was studied and crystal structure of compound (2) was determined. It was shown that all studied N-nitroxy succinimides inhibited cGMP phosphodiesterase in a concentration range of 0.1-0.001 mM. Compound (2) noncompetitively and reversibly inhibited hydrolytic function of enzyme with Ki=1.7×10—5 М. Inhibition constant for the reference compound N-(2-nitroethyl) nicotinamide (nicorandil) was 3×10—5 М. [ABSTRACT FROM AUTHOR]

The effect of iron nitrosyl complexes, NO donors, of a general formula [Fe2(L)2(NO)4] with functional sulfur-containing ligands (L-3-nitro-phenol-2-yl, 4-nitro-phenol-2-yl, or 1-methyl-tetrazol-5-yl) on the activity of sarcoplasmic reticulum Ca2+-ATPase and cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) was studied. The test complexes uncoupled the hydrolytic and transport functions of Ca2+- ATPase, thus disturbing the balance of Ca2+ ions in cells, which may affect the formation of thrombi and adhesion of metastatic cells to the endothelium of capillaries. They also inhibited the activity of cGMP PDE, thereby contributing to the accumulation of the second messenger cGMP. The studied iron nitrosyl complexes can be considered as potential drugs. [ABSTRACT FROM AUTHOR]

The prototype of uniquely designed complex data acquisition system for ITER divertor Thomson scattering diagnostic was developed. It allows recording short duration (3-5 ns) scattered pulses with 2 GHz sampling rate and 10-bit total resolution in oscilloscope mode. The system consists of 48 photo detector modules with 0-200 MHz bandwidth, 48 simultaneously sampling ADC modules and synchronization subsystem. The photo detector modules are based on avalanche photodiodes (APD) and ultra-low noise transimpedance amplifiers. ADC modules include fast analog to digital convertors and digital units based on the FPGA (Field-Programmable Gate Array) for data processing and storage. The synchronization subsystem is used to form triggering pulses and to organize the simultaneously mode of ADC modules operation. [ABSTRACT FROM PUBLISHER]

Electron transfer (ET) in the reaction center from Rhodopseudomonas viridis has been studied experimentally by our group in the range of temperatures of 153-295 K. The kinetics of ET reaction from the proximal heme of cytochrome to the special pair was found to be non-exponential. The degree of non-exponentiality strongly depends on temperature, with increasing non-exponentiality at lower temperatures. Here, the experimental kinetic data for ET are analyzed in the frames of a theoretical Sumi-Marcus-type model, which allows establishing a connection between the observed kinetics and local structural dynamics of the protein in a close vicinity of the donor and acceptor sites. The phenomenological model subdivides the multi-time-scale dynamics of the protein into two groups: fast and slow. The division is determined by the rate of ET, which is dynamically controlled by the slow modes of the protein medium. The slow modes are described by a phenomenological collective coordinate X, for which a diffusion type of dynamics is assumed. The analysis of the temperature dependence of the kinetic curves for ET allows a complete characterization of the slow time-scale protein dynamics: we find the corresponding activation barrier for the dynamics of X, around 0.5 eV and the exponential pre-factor, which is in the range of 10-16 s. The pre-exponential factor is lower than is expected for a typical activation process described by the transition state theory. We discuss the nature of the collective modes X, the nature of its activation barrier (breaking of hydrogen bonds) and possible explanations for a low-pre-exponential factor of its dynamics. The main conclusion of the paper is that the kinetics of ET at low-temperatures can be used as a probe of protein structural dynamics in the microsecond time-scale, the time-scale that is not easily accessible by the computer simulations methods and can be complementary to other experimental techniques. [ABSTRACT FROM AUTHOR]

[Display omitted] Two new heptamethine cyanine dye–fullerene C 60 covalently- linked dyads, which absorb in far-red and NIR spectral regions, have been synthesized by esterification click reaction and characterized by physicochemical methods. No significant fluorescence quenching was found due to weak electronic coupling between heptamethine moiety and fullerene core, which was confirmed by photophysical and electrochemical methods. Such dyads can be useful for cell imaging and fluorescence diagnostics of various fullerene derivatives. [ABSTRACT FROM AUTHOR]