邻氨基苯酚Schiff碱多核配合物的合成与表征

合成了3-羧基水杨醛缩邻氨基苯酚Sch iff碱及其三核铜,三核镍配合物.用质谱分析,核磁共振,红外光谱,元素分析对配体和配合物的结构进行了表征.磁性研究表明,这两种配合物的金属离子间均存在着较强的反铁磁性自旋交换相互作用.     

A theoretical study of the limits of the acidity of carbon acids in phase transfer catalysis in water and in liquid ammonia

The acidities of a large number of carbon acids have been theoretically calculated for the gas-phase and for DMSO solution. The gas-phase values, both ΔH and ΔG, are very well correlated with the available experimental data. From the calculated ΔG values in DMSO and the pKas in the same solvent, a homogeneous set of pK _a (DMSO) values was devised that was used to generate pK _a (water). These last pK _as were used to establish the limits of the acidity of carbon acids for reactions under PTC conditions both alkylations and H/D exchange. A step further led to the pK _as in liquid ammonia and from them to the virtual use of PTC using liquid ammonia instead of water.      

In silico study of cancer stage-specific DNA methylation pattern in White breast cancer patients based on TCGA dataset

BackgroundBreast cancer is one of the most common types of cancer among women. As current breast cancer treatments are still ineffective, we assess the methylation pattern of White breast cancer patients across cancer stage based on The Cancer Genome Atlas (TCGA) dataset. Significant hypermethylation and hypomethylation can regulate the gene expression, thus becoming potential biomarkers in breast cancer tumorigenesis.MethodsDNA methylation data was downloaded using TCGA Assembler 2 based on race-specific metadata of TCGA - Breast Invasive Carcinoma (TCGA-BRCA) project from Genomic Data Commons (GDC) Data Portal. After the data was divided into each cancer stage, duplicated data of each patient was removed using OMICSBind, while differentially-expressed probes were identified using edgeR. The resulting probes were validated based on correlation and regression analysis with the gene expression, ANOVA between cancer stages, ROC curve per stage, as well as databases.ResultsBased on the White dataset, we found 66 significant hypermethylated genes with logFC > 1.8 between Stage I-III. From this number, three epigenetic-regulated, stage-specific genes are proposed to be the detection biomarkers of breast cancer due to significant aberrant gene expression and/or low mutation ratio among breast cancer patients: ABCC9 (Stage III), SHISA3 (Stage II), and POU4F1 (Stage I-II).ConclusionsOur study shows that ABCC9, SHISA3, and POU4F1 are potential stage-specific detection biomarkers of breast cancer for White individuals, whereas their roles in other races need to be studied further.     

Molecular mechanism of the susceptibility difference between HLA-B*27:02/04/05 and HLA-B*27:06/09 to ankylosing spondylitis: substitution analysis,MD simulation,QSAR modelling,and in vitro assay

The human leukocyte antigen HLA-B27 is directly involved in the disease pathogenesis of ankylosing spondylitis (AS). HLA-B27 has a high degree of genetic polymorphism, with 105 currently known subtypes; the presence of aspartic acid at residue 116 (Asp116) has been found to play an essential role in AS susceptibility. Here, we systematically investigated the molecular mechanism of the susceptibility difference between the AS-associated subtypes HLA-B*27:02/04/05 and AS-unassociated subtypes HLA-B*27:06/09 to AS at sequence, structure, energetic and dynamic levels. In total seven variable residues were identified among the five studied HLA-B27 subtypes, in which Asp116 can be largely stabilized by a spatially vicinal, positively charged His114 through a salt bridge, while five other variable residues seem to have only a marginal effect on AS susceptibility. We also employed a quantitative structure–activity relationship approach to model the statistical correlation between peptide structure and affinity to HLA-B*27:05, a genetic ancestor of all other HLA-B27 subtypes and associated strongly with AS. The built regression predictor was verified rigorously through both internal cross-validation and external blind validation, and was then employed to identify potential HLA-B*27:05 binders from >20,000 cartilage-derived self-peptides. Subsequently, the binding potency of the top five antigenic peptides to HLA-B*27:05 was assayed in vitro using a FACS-based MHC stabilization experiment. Consequently, two (QRVGSDEFK and LRGAGTNEK) out of the five peptides were determined to have high affinity (BL₅₀ = 5.5 and 15.8 nM, respectively) and, as expected, both of them possess positively charged Lys at the C-terminus.     

Convenient synthesis of t-butyl Z-3-substituted glycidates under conditions of phase-transfer catalysis

Reactions of mixtures of t-butyl E- and Z-3-substituted glycidates 1a-h with 50% aq. sodium hydroxide and a catalyst, benzyltriethylammonium chloride, TEBAC in dichloromethane (phase-transfer catalysis, PTC) led to preferential hydrolysis of the E-isomers to afford pure (90-98%) t-butyl Z-3-substituted glycidates 1a-i in good yields; PTC cleavage of glycidates additionally substituted at C-2, 1g or C-3, 1h,i suggests that an aryl group in the Z isomers hampers attack of HO⁻ on the carbonyl carbon atom. As described in the literature, the diastereoselective PTC synthesis of Z-3-substituted glycidates and glycidonitriles consists of fast hydrolysis of E isomers present in mixtures with Z ones.     

Microbial transformations of buagarofuran,an anti-anxietic agent

19 structurally diverse metabolites (2–20) were isolated from the transformation of buagarofuran (1), an anxiety agent, by three filamentous fungal strains, Cunninghamella echinulata AS 3.3402, Cunninghamella elegans AS 3.3400, and Absidia coerulea AS 3.3538. Their structures and identified on the basis of extensive spectroscopic data (HRMS, NMR, IR, and CD) and chemical methods. All of the metabolites were oxidized products of 1, and metabolite 20 was also one of mammalian metabolites. Metabolites 8, 10–12, and 20 significantly inhibited [³H]-NE re-uptake, and 8 and 9 strongly inhibited [³H]-5-HT re-uptake in the rat brain synaptosomes at 10 μM in vitro. The structural diversity of the microbial transformed metabolites of buagarofuran in the present report would give a favorable opportunity to probe its mammalian metabolism and better shed light on its pharmacokinetics and pharmacodynamics in vivo.     

New accessory for studies of isotopic 1H/2H exchange and biomolecular interactions using transmission infrared spectroscopy

We present here a new accessory for IR transmission measurements of ¹H/²H exchange, as an ancillary tool for monitoring structural features of biomolecules in aqueous solution. This new accessory results from the combination of two dialysis membranes and a conventional liquid cell having two cylinders containing ²H₂O buffer. When compared with conventional transmission measurements, carried out either after dissolving lyophilized biomolecules in ²H₂O or after dialyzing the aqueous solution considered against ²H₂O buffer, this accessory shows the following advantages: (1) controlled measurements over the initial steps of this isotopic exchange and absence of molecular aggregation, and (2) smaller sample amounts. This new Fourier transform IR cell can also be used to analyze ligand–biomolecule and drug–cell interactions.      

Signalling probe displacement electrochemical aptasensor for malignant cell surface nucleolin as a breast cancer biomarker based on gold nanoparticle decorated hydroxyapatite nanorods and silver nanoparticle labels

Nucleolin is a multifunctional protein that is markedly overexpressed on the surface of most cancer cells. By taking advantage of the high affinity and specificity of the AS1411 aptamer for nucleolin, a signalling probe displacement electrochemical aptasensor was developed. The thiolated AS1411 aptamer was conjugated to hydroxyapatite nanorods (HApNRs) decorated with gold nanoparticles (AuNPs). To further increase the electrical conductivity of the interface, the ionic liquid 1-ethyl-3-methylimidazolium alanine with its high ion conductivity was placed on the electrode surface. Then, the aptamer was immobilized on the modified electrode and conjugated to signalling c-DNA tagged with AgNPs (c-DNA@AgNPs). In the presence of the MCF7 target cells, the signalling probe is displaced and released from the electrode surface. This leads to a decrease in the current that is proportional to the concentration of cancer cells in the range from 10 to 10⁶ cells mL^?1, with a detection limit as low as 8?±?2 cells mL^?1 (n?=?3) (based as 3σ/m, where σ is the standard deviation of the blank and m is the slope of the calibration plot). This method presents a promising tool for highly sensitive and selective detection of surface nucleolin on MCF7 cancer cells.

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Graphical abstract HApNR-AuNP-AS1411 aptamer nanocomposite as an electrochemical sensing interface was immobilized on the gold electrode surface and conjugated to signaling c-DNA tagged with AgNPs for determination of surface nucleolin on MCF7 cancer cells.

     

Electrochemical properties of polyaniline film doped by Ce3+ cation

Electrochemical Synthesis (ES)of polyaniline (PAni) is carried out in the presence in electrolyte (1 M H₂SO₄) of cerium (III) sulfate under potentiostatic and potentiodynamic modes. It is shown that Ce³⁺ cations in electrolyte catalyze ES, i.e. accelerate both ES variants. The obtained polymers were characterized using the scanning electron microscopy (SEM) technique and also on the basis of the calculation of electrochemical characteristics. Relaxation in PAni polymers doped by the Ce³⁺ cation occurs several times faster than in proton-doped PAni. The minimum change in ΔE and E is observed in polymers doped by Ce³⁺ cations during the electrochemical cycling of PAni and PAni-Ce at high rates.     

Serum metabolomics study of polycystic ovary syndrome based on UPLC-QTOF-MS coupled with a pattern recognition approach

Metabolomics has become an important tool in distinguishing changes in metabolic pathways and the diagnosis of human disease. Polycystic ovary syndrome (PCOS) is a relatively complicated, heterogeneous endocrine disorder. The etiology and pathogenesis of PCOS remain uncertain. In this study, based on the platform of ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and the method of pattern recognition, a comprehensive metabolomics approach has been applied to explore the changes in metabolic profiling between PCOS patients (n?=?20) and controls (n?=?15) as well as insulin-resistance (IR) PCOS patients (n?=?11) and non-IR PCOS subjects (n?=?9) in serum. In total, 36 metabolites were found significantly different between PCOS and controls, and 9 metabolites were discovered significantly different between IR and non-IR PCOS patients. Significant increases in the levels of saturated and unsaturated fatty acids (myristic acid, linoleic acid, 9-/13-HODE, etc.), fatty amides (palmitic amide, oleamide), dehydroepiandrosterone sulfate, l-glutamic acid, azelaic acid, l-glyceric acid, pyroglutamic acid, and decreases in the levels of lysophosphatidylethanolamine, lysophosphatidylcholine, uridine, and l-carnitine were found in PCOS patients compared with controls. In IR PCOS patients, linoleic acid, myristic acid, palmitoleic acid, and vaccenic acid also increased significantly compared with non-IR PCOS patients. All these changed metabolites showed abnormalities of steroid hormone biosynthesis, amino acids and nucleosides metabolism, glutathione metabolism, and lipids and carbohydrates metabolism in PCOS patients. The subgroup IR PCOS patients exhibited greater metabolic deviations than non-IR PCOS patients. These findings may help yield promising insights into the pathogenesis and advance the diagnosis and prevention of PCOS.

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Graphical Abstract Serum metabolomics signature of polycystic ovary syndrome

     

Synthesis and reactivity of(\mu - H)(\mu _3 - \eta ^2 - H_2 )_4 )Os_3 (CO)_9 : An unusually reactive triosmium cluster

The synthesis of $(\mu - H)(\mu - \eta ^2 - H_2 )_4 )Os_3 (CO)_{10} $ (4) from piperidine and Os₃(CO)₁₀(CH₃CN)₂ and its solid state structure are reported. The room temperature reactions of the decarbonylation product of4, $(\mu - H)(\mu _3 - \eta ^2 - H_2 )_4 )Os_3 (CO)_9 $ (3), with P(C₆H₅)₃, CNCH₃, HCl and H₂ are reported. Overall, the products obtained closely resemble those obtained from the analogous, $(\mu - H)(\mu _3 - \eta ^2 - H_2 )_3 )Os_3 (CO)_9 $ (1). The isomerizations of the phosphine addition products $(\mu - H)(\mu - \eta ^2 - H_2 )_n )Os_3 (CO)_9 P(C_6 H_5 )_3 $ (n = 3,6a;n = 4,5a) have been studied by¹H-NMR techniques and the initial rearrangement was shown to be an intramolecular process. Slower conversion to the complex $(\mu - H)(\mu _3 - \eta ^2 - H_2 )_4 )Os_3 (CO)_8 P(C_6 H_5 )_3 $ (8) was observed and the solid state structure of this product is reported and compared with a related compound containing an ethyl,n-propylμ ₃-imidoyl ligand. Compound4 crystallizes in the triclinic space group Pl (#2) withZ= 2, and unit cell parametersa = 9.294(3) Å,b = 15.758(5) Å,c = 7.406(2) Å,a = 81.10(2)°,β=76.47(2)°,y =74.88(2)°, andV =1013(l) ų. Least-squares refinement of 2677 reflections gave a final discrepancy factor ofR = 0.054 (R _w = 0.066). Compound8 crystallizes in the space group C2/c with unit cell parametersa = 24.818(3) Å,b = 16.389(3) Å,c = 18.111(3) Å,β= 120.94(2)°,V = 6318(4) ų, andZ = 8. Least squares refinement of 3439 reflections gave a final discrepancy factor ofR = 0.039 (R _w =0.047).     

Modified Quadrupole Ion Trap Mass Spectrometer for Infrared Ion Spectroscopy: Application to Protonated Thiated Uridines

Modifications to a Paul-type quadrupole ion trap mass spectrometer providing optical access to the trapped ion cloud as well as hardware and software for coupling to a table-top IR optical parametric oscillator laser (OPO) are detailed. Critical experimental parameters for infrared multiple photon dissociation (IRMPD) on this instrument are characterized. IRMPD action spectra, collected in the hydrogen-stretching region with this instrument, complemented by spectra in the IR fingerprint region acquired at the FELIX facility, are employed to characterize the structures of the protonated forms of 2-thiouridine, [s²Urd+H]⁺, and 4-thiouridine, [s⁴Urd+H]⁺. The measured spectra are compared with predicted linear IR spectra calculated at the B3LYP/6-311+G(d,p) level of theory to determine the conformers populated in the experiments. This comparison indicates that thiation at the 2- or 4-positions shifts the protonation preference between the 2,4-H tautomer and 4-protonation in opposite directions versus canonical uridine, which displays a roughly equal preference for the 2,4-H tautomer and O4 protonation. As found for canonical uridine, protonation leads to a mixture of conformers exhibiting C2′-endo and C3′-endo sugar puckering with an anti nucleobase orientation being populated for both 2- and 4-thiated uridine.

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Graphical Abstract ?

     

Organoruthenium(II) thiosemicarbazone complexes: synthesis, spectral characterization, DNA binding and DNA cleavage studies

A series of new ruthenium(II) complexes were synthesized with Schiff bases derived from salicylaldehyde / o-hydroxyacetophenone/ o-vanillin / 2-hydroxy-1-naphthaldehyde with thiosemicarbazide and acetyl furan. They are characterized by elemental analysis, IR, electronic, ¹H NMR, ¹³C NMR and mass spectral studies. The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). Four of these complexes were tested for its binding with CT-DNA using absorption spectroscopic studies and two of these complexes exhibit efficient DNA cleavage activity.      

Validated LC Method for Determination of Enantiomeric Purity of Apremilast Using Polysaccharide-Type Stationary Phases in Polar Organic Mode

Enantioseparation of an anti-psoriatic agent, apremilast (APR), was performed by HPLC using polysaccharide-type chiral stationary phases in polar organic mode for the first time. The separation capability of six different chiral columns (Chiralpak AD, Chiralpak IA, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) was investigated using neat MeOH and ACN. During the preliminary experiments the best results were obtained on Chiralpak IA column with ACN (R_s?=?5.4). The effects of binary mobile phases on the resolutions and retention factors were also investigated containing different percentages of MeOH:ACN. U-shaped retention pattern was obtained when plotting the retention factors of the APR enantiomers versus the MeOH content of the binary mobile phases on Chiralpak IA column. For further method optimizations an L25 orthogonal array table was employed altering the concentration of MeOH in ACN, column temperature, and flow rate. The best result was achieved on Chiralpak IA column with 80/20 (v/v%) MeOH/ACN with 0.7 mL min^?1 flow rate at 25 °C (R_s?=?5.4, t₂?=?7.45 min). Thermodynamic analysis revealed an enthalpy-driven enantioseparation. The developed HPLC method was validated according to the ICH guideline Q2(R1) and proved to be reliable, linear, precise and accurate for the determination of 0.1% R-enantiomer as chiral impurity in S-APR as well as quantification of the S-enantiomer.

Graphical Abstract

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Charge transfer in systems of conjugated bonds in cyanobiphenyl molecules: Quantum-chemical calculations of the structure and vibrational spectra

Quantum-chemical calculations of the IR absorption spectra and geometric and electronic structure of cyanobiphenyl molecules

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(I) were performed for various angles between benzene ring planes by the B3LYP/6-31+G** method. It was shown that the stablest conformation of I (X=OCH₃, OC₃H₇) should be the twist conformation with α= 37°, which was in agreement with the gas-phase experimental data. Rotation of benzene rings with respect to each other changed the relative orientation of the interacting π orbitals of the bridge ring carbon atoms and caused charge redistribution over molecule atoms, in particular, over terminal X and CN group atoms. The calculated period of charge oscillations on the alkyl and nitro groups coincided with the period of reversible charge transfer (～5–10 fs) between the conjugated subsystems (benzene ring + substituent) observed as the α angle changed. The rate of charge transfer between the electron donor and electron acceptor groups was calculated to be (3–6)×10⁵ m/s. Charge oscillations on benzene ring carbon atoms and donor and acceptor groups did not cause similar dipole moment oscillations and vibrations in the IR spectrum. The dipole moment of the molecule decreases as the angle between benzene ring planes increases, and the passage to the “perpendicular” conformation should increase the C≡N stretching vibration frequency by ～5 cm^?1 and decrease the intensity of the IR band by ～2 times. The elongation of the aliphatic chain in the X group did not cause noticeable changes in the geometric and electronic structure of the molecule.

     

New methodology for the preparation of N-tosyl aziridine-2-carboxylates

N-Tosyl aziridine-2-carboxylate methyl esters were prepared from methyl N-tosyl-l-serinate or N-tosyl-l-threoninate, tosyl chloride, and K₂CO₃, under phase-transfer catalysis (PTC) conditions. The same methodology, as applied to the tert-butyl N-tosyl-l-serine amide, afforded the corresponding newly prepared aziridine-2-carboxamide, as an enantiomerically pure compound.     

Kinetik der Reaktion von Sulfhydrylverbindungen mit α,β-ungesättigten Aldehyden in wäßrigem System

2-alkenals react with SH-compounds to R?CH(SR)?CH₂?CHO; 4-hydroxy-2-alkenals react to the corresponding 4-hydroxy-alkanals which rearrange to the cyclic semiacetals \(\begin{gathered} R\_CH\_CH(SR)\_CH_2 \_CHOH \\ |\_\_\_\_\_\_\_O\_\_\_\_\_\_\_| \\ \\ \end{gathered} \) . The overall-reaction is reversible. The rate of product formation is given by:v=k (alkenal) (sulfhydryl). Methods for determination of the rate constantk are described. The apparent constantk is a function of concentration and kind of proton donors of the reaction system (H₂O, H₃O⁺, CH₃COOH, H₂PO₄ ^?1, HPO₄ ^?2 or other HX-compounds). An equation is developed which describes the interrelation between the overall-reaction rate constantk and the individual intrinsic rate constants and composition of the reaction system. By this formula from thek-values the individual intrinsic rate constants of some model reactions are calculated. The biological effects of hydroxyalkenals are discussed on the basis of the obtained data.     

Formation of nanoparticles of a new metastable copper compound in the copper acetate hydrate/poly(acrylonitrile) heterogeneous system

We use X-ray powder diffraction to study heterogeneous solid-phase reactions induced by IR radiation in the system Cu(OOCCH₃)₂·H₂O/PAN and intermediate copper compounds in the synthesis of copper nanoparticles. The composite Cu(OOCCH₃)₂ · H₂O/PAN after annealing contains crystallites of copper (l _Cu = 16 nm), a new metastable compound Cu _x>2O ( $ l_{Cu_{x > 2} O} We use X-ray powder diffraction to study heterogeneous solid-phase reactions induced by IR radiation in the system Cu(OOCCH₃)₂·H₂O/PAN and intermediate copper compounds in the synthesis of copper nanoparticles. The composite Cu(OOCCH₃)₂ · H₂O/PAN after annealing contains crystallites of copper (l _Cu = 16 nm), a new metastable compound Cu _x>2O ( = 20 nm), and Cu₂O ( = 20 nm). After 45 days of air exposure, the intensity of Cu _x>2O reflections in the composite decreases dramatically, whereas that of copper reflections increases. Cu _x>2O has a monoclinic unit cell with the parameters a = 5.424, b = 3.196, c = 3.072 ?, β = 119.51°. Original Russian Text ? V.M. Novotortsev, V.V. Kozlov, Yu.M. Korolev, G.P. Karpacheva, L.V. Kozhitov, 2008, published in Zhurnal Neorganicheskoi Khimii, 2008, Vol. 53, No. 7, pp. 1087–1089.