QM/MM modeling of the hydroxylation of the androstenedione substrate catalyzed by cytochrome P450 aromatase (CYP19A1)

CYP19A1 aromatase is a member of the Cytochrome P450 family of hemeproteins, and is the enzyme responsible for the final step of the androgens conversion into the corresponding estrogens, via a three‐step oxidative process. For this reason, the inhibition of this enzyme plays an important role in the treatment of hormone‐dependent breast cancer. The first catalytic subcycle, corresponding to the hydroxilation of androstenedione, has been proposed to occur through a first hydrogen abstraction and a subsequent oxygen rebound step. In present work, we have studied the mechanism of the first catalytic subcycle by means of hybrid quantum mechanics/molecular mechanics methods. The inclusion of the protein flexibility has been achieved by means of Free Energy Perturbation techniques, giving rise to a free energy of activation for the hydrogen abstraction step of 13.5 kcal/mol. The subsequent oxygen rebound step, characterized by a small free energy barrier (1.5 kcal/mol), leads to the hydroxylated products through a highly exergonic reaction. In addition, an analysis of the primary deuterium kinetic isotopic effects, calculated for the hydrogen abstraction step, reveals values (～10) overpassing the semiclassical limit for the C? H, indicating the presence of a substantial tunnel effect. Finally, a decomposition analysis of the interaction energy for the substrate and cofactor in the active site is also discussed. According to our results, the role of the enzymatic environment consists of a transition state stabilization by means of dispersive and polarization effects. © 2015 Wiley Periodicals, Inc.     

X-ray crystallographic structure and physical properties of the pentacoordinated [TPAFeCl] complex

A new pentacoordinated ferrous compound [TPAFeCl]⁺ (TPA = tris(2-pyridylmethyl)amine) was synthesized from the reaction between H₃TPA(ClO₄)₃ and Fe(PⁿPr₃)₂Cl₂ in MeCN. The unique trigonal bipyramidal [TPAFeCl]⁺ complex was characterized as a S = 2 high spin complex based on the crystallographic structure, magnetic susceptibility, ¹H NMR spectrum and semi-empirical ZINDO/S calculations. Crystal of [TPAFeCl]₂(FeCl₄)(MeCN)₂ was monoclinic with a = 12.019(2) Å, b = 27.550(5) Å, c = 14.138(2) Å, β = 94.168(3)°, V = 4668.9(13) Å³, space group C/c, and the unit cell contained a racemic mixture of Δ and Λ isomers with ferrous tetrachloride anion.     

硼烯化合物的合成及应用

In most cases, borylenes containing boron (I) are unstable. In this article, we proceed from the electron configuration of borylene and review the common methods of stabilizing this category of compounds through a series of borylenes in literature. In addition, the article briefly introduces the metallic borylenes and non-metallic borylenes and their properties. Some of these properties have been applied in nitrogen fixation.     

Novel and Efficient One Pot Condensation Reactions between Ketones and Aromatic Alcohols in the Presence of CrO3 Producing α,β‐Unsaturated Carbonyl Compounds

We report a new, effective and simple method for preparing α,β‐unsaturated carbonyl compounds by reacting ketones and aromatic alcohols at 56°C in the presence of CrO₃ (CrO₃ acts as an oxidant and also a catalyst) for around 10 h. The condensation reactions occurred effectively among a wide combination of ketones and alcohols. The procedure is simple and the yields can be high up to 98%. And a probable mechanism is proposed.     

Thermal stability of the layered modification of Cu0.5ZrTe2 in the temperature range 25–900 °C

The thermal stability of the layered modification of the Cu_0.5ZrTe₂ polycrystalline intercalation compound, synthesized at room temperature, has been studied in the temperature range 25–900 °C. A change in the occupation of the octahedral and tetrahedral coordinated sites in the interlayer space of the zirconium ditelluride was observed using in‐situ time‐resolved synchrotron X‐ray powder diffraction experiments. The formation of the rhombohedral CuZr₂Te₄ phase, which is stable in the temperature range 300–700 °C, has been observed. The copper intercalation at room temperature leads to the formation of a phase in which the Cu atoms occupy only octahedral sites in the interlayer space. At temperatures above the decay temperature of the rhombohedral CuZr₂Te₄, a layered phase with Cu atoms uniformly distributed between octahedral and tetrahedral sites in the interlayer space is stable. The changes in the crystal structure independent of temperature are in agreement with the previously proposed model, according to which the stability of the layered or the rhombohedral phase is determined by the entropy factor associated with the distribution of the intercalated atoms between the octahedral and tetrahedral sites in the interlayer space.     

A New Compound—Nanoline K2Ti8O15

In the product of carbon made from tar oil by plasma pyrogenation, some nanowires, whose diameter is 9~20 nm and whose length is 300 nm were found. The result of X-ray Energy Dispersed Spectrum (EDS) indicated that it is a new compound K2Ti8O15, which has never been reported before. Compared with the corresponding stoichiometry compound K2Ti8O15, it is a non-stoichiometry compound in which two oxygen atoms are absent. It is due to the fact that the intensive deoxidization occured in the experimental process and the valence of titalium is alterable. Its microstructure in detail by high revolution electromicroscopy (HREM) and X-ray diffraction were studied.     

铽、铕-邻啡啰啉-芳香化合物三元配合物的合成和性质研究

本文对Ln(phen)(C₆H₅COO)₃、Ln(phen)₂P-(OC₆H₄CHO)₃·3H₂O.Ln(phen)₂P-(OC₆H₄COOC₂H₅)₃(Ln=Tb、Eu)固体配合物的制备和光谱性质进行了研究。根据元素分析、红外光谱、摩尔电导测定,X射线粉末衍射、热重差热分析以及紫外可见光谱确定了其组成及配位形式,并对其发光性能进行了研究。     

Synthesis and Structure of K_3Na_3〔MnMo_9O_(32)〕·6H_2O

1INTRODUCTIONHeteroPOlymolybdatesareknownwithaverywiderangeofmetalionsithetypeandstabilityoftheclustersshowdependenceonboththeheteroatomandPH"'.TheknownheteroPOlymolybdateswhichincludemanganese(1)ormanganese(IV)havebeenreported.Afewofhetercrg-molybdateanionswiththemanganese(IIV)andnickel(IV)formsarecharacterizedandisostructural[2).Thesehigheroxidationstatespecieshavebeenpreparedpreviouslybyoxidationoflower--valentspecieswithPOwerfuloxidant,suchasPeroxydisulfateorPeroxymonosulfurica…     

Phase Relations in The V2O5–MoO3–α-Sb2O4 System in The Solid State in Air Atmosphere

The phase equilibria established in the V₂O₅–MoO₃–α-Sb₂O₄ system in the solid state in an air atmosphere were examined by using XRD and DTA methods. The obtained results allowed us to find that in this system a novel compound is formed involving three oxides. Its formula can be written as Sb₃V₂Mo₃O₂₁. The synthesis of this compound requires picking up the atmospheric oxygen. X-ray characteristics of this compound were determined and it was found that it melted incongruently at 740°C. The results obtained until now allow us to divide the investigated V₂O₅–MoO₃–α-Sb₂O₄ system into five partial subsystems. This revised version was published online in July 2006 with corrections to the Cover Date.