Reaction mechanism of soluble epoxide hydrolase: insights from molecular dynamics simulations

Molecular dynamics simulations have been performed to gain insights into the catalytic mechanism of the hydrolysis of epoxides to vicinal diols by soluble epoxide hydrolase (sEH). The binding of a substrate, 1S,2S-trans-methylstyrene oxide, was studied in two conformations in the active site of the enzyme. It was found that only one is likely to be found in the active enzyme. In the preferred conformation the phenyl group of the substrate is pi-sandwiched between two aromatic residues, Tyr381 and His523, whereas the other conformation is pi-stacked with only one aromatic residue, Trp334. Two simulations were carried out to 1 ns for each conformation to evaluate the protonation state of active site residue His523. It was found that a protonated histidine is essential for keeping the active site from being disrupted. Long time scale, 4 ns, molecular dynamics simulation was done for the structure with the most likely combination of binding conformation and protonation state of His523. Near Attack Conformers (NACs) are present 5.3% of the time and nucleophilic attack on either epoxide carbon atom, approximately 75% on C(1) and approximately 25% on C(2), is found. A maximum of one hydrogen bond between the epoxide oxygen and either of the active site tyrosines, Tyr465 and Tyr381, is present, in agreement with experimental mutagenesis results that reveal a slight loss in activity if one tyrosine is mutated and essential loss of all activity upon double mutation of the two tyrosines in question. It was found that a hydrogen bond from Tyr465 to the substrate oxygen is essential for controlling the regioselectivity of the reaction. Furthermore, a relationship between the presence of this hydrogen bond and the separation of reactants was found. Two groups of amino acid segments were identified each as moving collectively. Furthermore, an overall anti-correlation was found between the movements of these two individually collectively moving groups, made up by parts of the cap-region, including the two tyrosines, and the site of the catalytic triad, respectively. This overall anti-correlated collective domain motion is, perhaps, involved in the conversion of E.NAC to E.TS.     

Toward separation of nuclear spin isomers with coherent light.

We propose an approach for separating nuclear spin isomers with coherent light and illustrate it by numerical calculations using fulvene as a model system. The scheme employs the equivalence of torsion and interchange of equivalent H-atoms in a class of molecules of which fulvene is a simple example. The exchange symmetry couples with the rotational symmetry to produce a spatial distinction between the two photo-excited nuclear spin isomers, and wavepacket interferometry is applied to separate the species.     

The ETACS European project for testing the comparability of sensors and analysers

ETACS is the official acronym for the European project "European Testing and Assessment of Comparability of On-line Sensors/Analysers". This project has three main objectives to achieve the comparability of performance data for sensors and analysers in the environmental field. First, to develop a test protocol for validation and comparison of the performance of on-line sensors/analysers. The test protocol is intended to be generic, that is independent of the specific sensors/analysers and the specific parameters to be monitored. Second, the practical testing of this test protocol to assess its applicability and to develop the techniques used. Finally, to achieve widespread acceptance of the test protocol by producer/suppliers, users and relevant authorities to assist its early adoption as an agreed European standard. Laboratory tests for producing the test protocol have been carried out and completed to check the applicability of such a protocol.     

Separation and determination of alditols and sugars by high-pH anion-exchange chromatography with pulsed amperometric detection

Carbohydrates such as alditols (polyols or sugar alcohols), monosaccharides and disaccharides are separated as anions by anion-exchange chromatography with a sodium hydroxide eluent, MA1 CarboPac column and pulsed amperometric detection. We report a high-pH anion-exchange chromatographic-pulsed amperometric detection (HPAEC-PAD) method that determines all the polyols used as food additives in food products and the most commonly found mono- and disaccharides on a routine basis. The linearity, repeatability, internal reproducibility and accuracy are described. The applicability of the method has been demonstrated by the analysis of 46 relevant samples and by participation twice in the Food Analysis Performance Assessment Scheme (FAPAS) testing programme for food additives.     

Can the highest occupied molecular orbital of the uranyl ion be essentially 5f?

Recent relativistic calculations on the uranyl ion suggest that the low wave numbers of the first electron transfer bands are due to a bonding 5f-like orbital containing the two loosest bound electrons. Comparison with UF₆ makes it more likely that if indeed σ_u (and not π_u) is the highest occupied MO, it is rather due to “pushing from below” by U 6p (like N 2s in N₂).     

Theoretical analysis of the electronic structure and molecular properties of thioborine,HSB and comparison with related compounds. An ab initio mo-cal

Ab initio calculations on the thioborine molecule have been performed. Ionization potentials, force constants and geometry parameters are calculated in fair agreement with experimental values. A preliminary investigation of the sensitivity by nucleophilic attack has also been performed, indicating a rather strong tendency to undergo that type of reaction.     

Magnetic field dependence of the spin—spin relaxation time of ferric ions in Fe(NO3)3·9H2O and in frozen aqueous solutions

The electronic relaxation of ferric ions in Fe(NO₃)₃·9H₂O and in frozen aqueous solutions has been investigated by use of Mössbauer spectroscopy. The application of an external magnetic field causes a pronounced increase of the spin—spin relaxation time, an effect which is contrary to that normally found in ferric compounds. An explanation is given based on a difference in the ionic state energies of the neighbouring ions induced by the applied magnetic field.     

Rationalisation of weak ferromagnetism in manganese(III) chains: the relation between structure and ordering phenomena

The synthesis, structure and magnetic properties of the one-dimensional chain compounds [Mn(cyclam)(SO4)]ClO4.H2O (1) and [Mn(cyclam)(HCOO)](CF3SO3)(ClO4) (2) are reported. Cyclam is the cyclic tetradentate ligand 1,4,7,11-tetraazacyclotetradecane. Both chain compounds exhibit antiferromagnetic interactions within the chains. A magnetic ordering phase transition at 5.5 K in (1) is investigated by magnetisation measurements along the three principal crystallographic axes of a single crystal and the results show unambiguously that the ferromagnetic ordering is only taking place along one crystallographic axis. The spin structure of the magnetic ordered phase and the magnitude of the ferromagnetic moment are correlated with the crystal structure and symmetry of the compound.     

Pyrazine-2,3-dicarbonitriles substituted with maleimide derivatives

Syntheses and spectroscopic characteristics are reported for eight pyrazine-2,3-dicarbonitriles substituted with maleimide residue in addition to phenyl, 2-thienyl, or 2-furyl substituent. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1409–1414, September, 2007.