10 α -Hydroxy- β -isomorphine, a by-product of the synthesis of 10 α -hydroxymorphine

Abstract  

A new compound was isolated from the reaction mixture after O-demethylation of 6-O-acetyl-10α-acetoxycodeine with boron tribromide. The structure of this compound, 10α-hydroxy-β-isomorphine, was elucidated by spectral data, and its spatial arrangement was deduced from an NOE experiment. Capillary zone electrophoresis was used for separation of morphine and its 10-hydroxy analogues.     

Identifying hQC Inhibitors of Alzheimer’s Disease by Effective Customized Pharmacophore-Based Virtual Screening,Molecular Dynamic Simulation,and Binding Free Energy Analysis

Applied Biochemistry and Biotechnology - Human glutaminyl cyclase (hQC) appeared as a promising new target with its inhibitors attracted much attention for the treatment of Alzheimer’s...     

Automatic simulation of electrochemical transients by the adaptive Huber method for Volterra integral equations involving Kernel terms exp[?α(t ? τ)]erex{[β(t ? τ)]1/2} and exp[?α(t ? τ)]daw {[β(t ? τ)]1/2}

Development of fully automatic methods for the simulation of transient experiments in electroanalytical chemistry is a desirable element of the contemporary trends of laboratory automation in electrochemistry. In accord with this idea, the adaptive Huber method, elaborated by the present author, is intended to solve automatically integral equations of Volterra type, encountered in the theory of controlled-potential transients. The coefficients of the method have been recently obtained for integral transformation kernels involving terms K(t, τ) = exp[−α(t − τ)]erex{[β(t − τ)]^1/2} and K(t, τ) = exp[−α(t − τ)]daw{[β(t − τ)]^1/2} with α ≥ 0 and β ≥ 0, which are known to occur in the above integral equations. In this work the validity of the resulting method, for electrochemical simulations, is examined using representative examples of electroanalytical models involving integral equations with various special cases of such kernel terms. The performance of the method is found similar to that previously reported for integral equations involving exclusively kernels K(t, τ) = 1, K(t, τ) = (t − τ)^−1/2, and K(t, τ) = exp[−λ (t − τ)](t − τ)^−1/2 with λ > 0.     

In situ construction of ligand nano-network to integrin αvβ3 for angiogenesis inhibition

Angiogenesis occurs during the process of tumor growth, invasion and metastasis, and is essential for the survival of solid tumors. As an integrin significantly overexpressed in human tumor vascular endothelial cells, α_vβ₃ is a suitable targeting site for anti-angiogenesis of tumor. We designed and prepared a selfassembling peptide (SAP) with the ability to targeting α_vβ₃ and self-assembly. SAP formed nanoparticles in solution and transformed into nanofibrous network once specifically binding to integrin α_vβ₃ on the surface of human umbilical vein endothelial cells (HUVECs). The SAP network stably anchored on HUVECs over 24 h, which consequently resulted in high-efficient inhibition of vascularization. In vitro anti-angiogenesis experiment displayed that the inhibition rate of tube-formation reached 94.9%. In vivo anti-angiogenesis array based on chick chorioallantoic membrane (CAM) model exhibited that the SAP had an inhibition rate up to 63.1%. These results indicated the outstanding anti-angiogenic ability of SAP, potentially for tumor therapy.     

Selection of protecting groups and synthesis of a β-1,4-GlcNAc-β-1,4-GlcN unit

Abstract  

The synthesis of the disaccharide tert-butyldimethylsilyl (4-O-acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside, designed as a repeating unit appearing in oligo- and polysaccharides, which exhibits a distinguished “obverse–reverse” property in β-1,4-glucan chain, was accomplished. This disaccharide was synthesized by glycosylation of a phthalimido sugar with an azido sugar. A selective removal of the two different protecting groups at C-2 for obtaining 2-acetamido-4-O-(2-amino-2-deoxy-β-d-glucopyranosyl)-2-deoxy-β-d-glucopyranose indicates that the selection and combination, using phthalimido and azido as protecting groups, are an excellent strategy for synthesizing such target disaccharides.     

Sol–gel synthesis and characterization of SBA-15 in presence of metalloporphyrins: m-5,10,15,20 TPP-Ni2+, Etio-III-Ni2+ and Etio-III-VO2+

New mesoporous materials were produced incorporating, at the beginning of the SBA-15 sol–gel synthesis, three different metalloporphyrins: m-5,10,15,20-TPP-Ni²⁺, Etio-III-Ni²⁺, Etio-III-VO²⁺. These materials have the well-known hexagonal structure characteristic of SBA-15 with some differences: the presence of the porphyrins modifies the micelles generated during the sol–gel process changing the textural properties of the SBA-15-Porphyrins. Even when the hexagonal structure was preserved, the order in the crystalline structure was maintained only for short distances producing pores of different sizes and wider pore size distributions. UV–Vis results showed that the porphyrins are strongly adsorbed on SBA-15 through the interaction of their π electrons with the superficial hydroxyl groups of the support. This was confirmed by thermogravimetric results that show a high degree of incorporation of the porphyrins on the SBA-15 and a high thermal stability.     

Protein Flexibility and Multiple Docking in Ligand Docking and Virtual Screening to the BRAF (Type Ⅰ1/2) Inhibitors

BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design(CADD). Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs(Glide, GOLD and Ligand Fit) and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening(VS). The most accurate results(mean RMSD of about 0.6 ?) of pose prediction were obtained with two complex structures(PDB: 3 C4 C and 3 SKC) using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.     

Essential Structure of Opioid κ Receptor Agonist Nalfurafine for Binding to κ Receptor 1: Synthesis of Decahydroisoquinoline Derivatives and Their Pharmacologies

On the basis of the three-dimensional pharmacophore model of opioid κ agonists, we simplified the structure of nalfurafine (selective κ agonist) to find the essential structural moieties for binding the opioid receptors, especially κ receptor type. As a result, we found that the trans-fused decahydroisoquinoline derivatives without a phenol ring bound the opioid receptor in micromolar order and that both the amide side chain and the nitrogen substituted by the cyclopropylmethyl group were indispensable moieties for eliciting the κ selectivity. The simple decahydroisoquinoline without amide side chain also bound the opioid receptor without receptor type selectivity, suggesting that the message-address concept would be applicable to even these simple derivatives. These findings that the simple decahydroisoquinoline derivatives showed the affinities for the opioid receptors, especially some of the compounds showed κ selectivity, are the first example in the opioid field.     

Sulfamic acid as a cost-effective and recyclable solid acid catalyst for Friedel–Crafts alkylation of indole with α,β-unsaturated carbonyl compound and benzyl alcohol

Sulfamic acid was proved to be a cost-effective and recyclable catalyst for Friedel-Crafts type reaction of indole withα,β-unsaturated carbonyl compound and benzyl alcohol.Various indoles,α,β-unsaturated carbonyl compounds and a benzyl alcohol were successfully used in this type of reaction,and the corresponding products were obtained in good to excellent yields.     

Synthesis of a chito-tetrasaccharide β-1,4-GlcNAc-β-1,4-GlcN repeating unit

Abstract  

tert-Butyldimethylsilyl (4-O-acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside (Kawada and Yoneda [MOCHEM-D-09-00120], 2009), designed as a repeating disaccharide unit in a β-glucan having two different faces, was converted into a glycosyl donor and an acceptor. The glycosyl acceptor was glycosylated with the donor to afford a chito-tetrasaccharide derivative in good yield. Phthalimido and azido groups in the tetrasaccharide were successively converted into acetamido and free amino groups, and all other protecting groups were cleaved to obtain the chito-tetrasaccharide (2-amino-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-(2-amino-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-2-acetamido-2-deoxy-d-glucopyranose.     

Synthesis and characterization of dinuclear p-, m- and o-xylyl bridged complexes of molybdenum and tungsten. The crystal structures of μ-p-xylyl- bis(η-pentamethyl-cyclopentadienyltri- carbonylmolybdenum) and μ-m-xylyl-bis(η- pentamethylcyclopentadienyltricarbonyltungsten)

The reactions of (M = Mo, W) with α,α′-p-, m- and o-dichloro-xylenes yielded p-, m- and o-xylyl bridged dinuclear complexes of in high yields. All of such new complexes are stable to air and water, even stable in dilute acids and bases.     

(p, ρ, T, x) properties for CO2/isobutane binary mixtures at T = (280 to 440) K and (3 to 200) MPa

The (p, ρ, T, x) properties for binary mixtures of CO₂ (volume fraction purity 0.99999) and isobutane (mole fraction purity 0.99988) {x₁ CO₂ + x₂ isobutane (x₁ = 0.2482, 0.4718, and 0.7506)} were measured in the compressed liquid phase using a metal-bellows variable volumometer. Measurements were conducted from T = (280 to 440) K and (3 to 200) MPa. The expanded uncertainties (k = 2) were estimated to be: temperature, <3 mK; pressure, 1.5 kPa (p ? 7 MPa), 0.06% (7 MPa < p ? 50 MPa), 0.1% (50 MPa < p ? 150 MPa), 0.2% (p > 150 MPa); density, 0.10%; and composition, 4.4 · 10⁻⁴. At >100 MPa and T = (280 or 440) K, the uncertainties in the density measurements increased to 0.14% and 0.22%, respectively. The data are compared with the available equation of state. The excess molar volumes, , of the mixtures were calculated and plotted as a function of temperature and pressure.     

Modeling Ar and Kr matrix effect on the ν s (Cl–H) and ν l (Cl–H) of Cl–H···NH3 by the IEF-PCM method

Ar and Kr matrix effect on the geometry and Cl–H stretching (ν _s (Cl–H)) and librational (ν _l (Cl–H)) frequencies of the hydrogen-bonded complex Cl–H···NH₃ are simulated within the framework of polarizable continuum model with integral equation formalism (IEF-PCM) at B3LYP and MP2 levels of theory with the basis set 6-311++G(2df,2pd). Within the framework of B3LYP and IEF-PCM, the simulated gas phase, Ar, and Kr matrix ν _s (Cl–H) of the complex are 2140, 1684, and 1550 cm⁻¹, respectively, which deviate from the experimental values (~2200, 1371, and 1218 cm⁻¹) by −60, 313, and 332 cm⁻¹. Within the framework of MP2 and IEF-PCM, the gas phase, Ar, and Kr matrix ν _s (Cl–H) are calculated as 2366, 2037, and 1957 cm⁻¹ by the harmonic approximation, and as 2177, 1876, and 1665 cm⁻¹ by the full-dimensional anharmonic correction. The matrix effect modeling is of greater importance than the anharmonic correction in accounting for the large experimental gas phase to Ar or Kr matrix shift of the ν _s (Cl–H) (−829 or −982 cm⁻¹). Our calculations do not support the assignment of the 733.8 and 736.9 cm⁻¹ bands to the Ar and Kr matrix ν _l (Cl–H).     

4β-Isocyanopodophyllotoxins: valuable precursors for the synthesis of new podophyllotoxin analogues

A new and efficient method for the synthesis of novel 4β-isocyanopodophyllotoxins as a valuable building block for the synthesis of versatile bioactive podophyllotoxin analogues under both classical and ultrasonic conditions was developed. In general, significant improvements in rates of reaction and yields of sonochemical reactions relative to the classical ones were observed.     

New (p, ρ, T) data for carbon dioxide – Nitrogen mixtures from (250 to 400) K at pressures up to 20 MPa

Comprehensive (p, ρ, T) measurements on two binary mixtures (0.10 CO₂ + 0.90 N₂ and 0.15 CO₂ + 0.85 N₂) were carried out in the gas phase at seven isotherms between (250 and 400) K and pressures up to 20 MPa using a single sinker densimeter with magnetic suspension coupling. A total of 69 (p, ρ, T) data for the first mixture and 69 (p, ρ, T) data for the second are presented in this article. The uncertainty in density was estimated to be (0.02 to 0.15)%, while the uncertainty in temperature was 3.9 mK and the uncertainty in pressure was less than 0.015% (coverage factor k = 2). Experimental results were compared with densities calculated from the GERG equation of state and with data reported by other authors for similar mixtures. Results yielded that, while deviations between experimental data and values calculated from the GERG equation were lower than 0.05% in density for low pressures, the relative error at high pressures and low temperatures increased to about (0.2 to 0.3)%. The main aim of this work was to contribute to an accurate density data base for CO₂/N₂ mixtures and to check or improve equations of state existing for these binary mixtures.     

Clustering Algorithms to Analyze Molecular Dynamics Simulation Trajectories for Complex Chemical and Biological Systems?

Molecular dynamics (MD) simulation has become a powerful tool to investigate the structurefunction relationship of proteins and other biological macromolecules at atomic resolution and biologically relevant timescales. MD simulations often produce massive datasets containing millions of snapshots describing proteins in motion. Therefore, clustering algorithms have been in high demand to be developed and applied to classify these MD snapshots and gain biological insights. There mainly exist two categories of clustering algorithms that aim to group protein conformations into clusters based on the similarity of their shape (geometric clustering) and kinetics (kinetic clustering). In this paper, we review a series of frequently used clustering algorithms applied in MD simulations, including divisive algorithms, agglomerative algorithms (single-linkage, complete-linkage, average-linkage, centroid-linkage and ward-linkage), center-based algorithms (K-Means, K-Medoids, K-Centers, and APM), density-based algorithms (neighbor-based, DBSCAN, density-peaks, and Robust-DB), and spectral-based algorithms (PCCA and PCCA+). In particular, differences between geometric and kinetic clustering metrics will be discussed along with the performances of different clustering algorithms. We note that there does not exist a one-size-fits-all algorithm in the classification of MD datasets. For a specific application, the right choice of clustering algorithm should be based on the purpose of clustering, and the intrinsic properties of the MD conformational ensembles. Therefore, a main focus of our review is to describe the merits and limitations of each clustering algorithm. We expect that this review would be helpful to guide researchers to choose appropriate clustering algorithms for their own MD datasets.     

Synthesis and electrochemical properties of LiNi0.85 ? x Co x Mn0.15O2 as cathode materials for lithium-ion batteries

LiNi_0.85−x Co _x Mn_0.15O₂ cathode material was prepared by a rheological phase reaction method with LiNO₃, M(NO₃)₂ 6H₂O (M = Ni, Co, Mn), and citric acid as starting materials. The mixture of reactants and a proper amount of water reacted to form a rheological precursor. The rheological precursor was pretreated in autoclaves and then calcined at 750 °C under flowing oxygen. All the samples have a typical layered structure with space group R3-m and good electrochemical performances. The cobalt content has a significant effect on the electrochemical performance for the materials. LiNi_0.65Co_0.20Mn_0.15O₂ exhibits the best electrochemical properties in the five compounds. It gives an initial discharge capacity of 173.6mAhg⁻¹ (50mA g⁻¹, 3.0−4.3V), and the capacity rention after 50 cycles is 90.6%. This method is simple and effective for preparing cathode materials for lithium-ion batteries.     

Theoretical Study of Chemical Binding of Noble Gas Atom and Transition Metal Complexes: Ng–NiCO, Ng–NiN2, Ng–CoCO (Ng = He–Xe)

Summary. Ab initio multireference and coupled cluster methods (MR-SDCI(+Q), CASPT2, CCSD(T)) and density functional theory methods (B3LYP, MPWPW91) have been applied to examine geometrical structures and vibrational frequencies of noble gas (Ng) – transition metal compounds, Ng–NiCO, Ng–NiN₂, and Ng–CoCO (Ng = He, Ne, Ar, Kr, Xe). It is shown that the respective compounds can have a larger binding energy than a typical van der Waals interaction energy. The binding mechanism is explained by a partial electron transfer from a noble gas atom to the low-lying 4s and 3d vacant orbitals of the transition metal atom. Theoretical calculations show that the binding of noble gas atom results in a large shift of the bending frequency: 361.1cm^–1 (NiCO) to 403.5cm^–1 (Ar–NiCO); 308.5cm^–1 (NiN₂) to 354.8cm^–1 (Ar–NiN₂); 373.0cm^–1 (CoCO) to 422.6cm^–1 (Ar–CoCO). The corresponding experimental frequencies determined in solid argon are 409.1cm^–1 (NiCO), 357.0cm^–1 (NiN₂), and 424.9cm^–1 (CoCO), which are much closer to the corresponding frequency of Ar–NiCO, Ar–NiN₂, and Ar–CoCO, respectively.     

Theoretical Study of Chemical Binding of Noble Gas Atom and Transition Metal Complexes: Ng–NiCO, Ng–NiN2, Ng–CoCO (Ng = He–Xe)

Ab initio multireference and coupled cluster methods (MR-SDCI(+Q), CASPT2, CCSD(T)) and density functional theory methods (B3LYP, MPWPW91) have been applied to examine geometrical structures and vibrational frequencies of noble gas (Ng) – transition metal compounds, Ng–NiCO, Ng–NiN₂, and Ng–CoCO (Ng = He, Ne, Ar, Kr, Xe). It is shown that the respective compounds can have a larger binding energy than a typical van der Waals interaction energy. The binding mechanism is explained by a partial electron transfer from a noble gas atom to the low-lying 4s and 3d vacant orbitals of the transition metal atom. Theoretical calculations show that the binding of noble gas atom results in a large shift of the bending frequency: 361.1cm^–1 (NiCO) to 403.5cm^–1 (Ar–NiCO); 308.5cm^–1 (NiN₂) to 354.8cm^–1 (Ar–NiN₂); 373.0cm^–1 (CoCO) to 422.6cm^–1 (Ar–CoCO). The corresponding experimental frequencies determined in solid argon are 409.1cm^–1 (NiCO), 357.0cm^–1 (NiN₂), and 424.9cm^–1 (CoCO), which are much closer to the corresponding frequency of Ar–NiCO, Ar–NiN₂, and Ar–CoCO, respectively.     

Structural investigations of β-CaAlF5 by coupling powder XRD, NMR, EPR and spectroscopic parameter calculations

β-CaAlF₅ was synthesized by solid-state reaction. The precise structure was refined from X-ray powder diffraction data in the monoclinic space group P2₁/c with lattice constants , , , and β=109.91° (Z=4). The structure exhibits isolated chains of octahedra sharing opposite corners.¹⁹F and ²⁷Al solid state NMR spectra were recorded using MAS and SATRAS techniques. An EPR spectrum was recorded for β-CaAlF₅:Cr³⁺. The experimental spectra were simulated in order to extract the NMR and EPR parameter values. Five fluorine sites and one low symmetry aluminium site were found in agreement with the refined structure.These parameters were calculated using empirical and ab-initio methods. The agreement obtained between the calculated ¹⁹F chemical shift values, ²⁷Al quadrupolar parameters, Cr³⁺ EPR fine structure parameters and the experimental results demonstrates the complementarity of XRD, magnetic resonance experiments and theoretical methodologies.