Epoxides related to dioncoquinone B: Synthesis,activity against multiple myeloma cells,and search for the target protein

Epoxide 2b is an analog of the synthetic intermediate 2a en route to the polyketide-derived antitumoral naphthoquinone dioncoquinone B (1), isolated from cell cultures of the tropical liana Triphyophyllum peltatum (Dioncophyllaceae). Compound 2b was found to induce strong apoptosis in multiple myeloma cells at a concentration (EC₅₀?=?3.5?μM), distinctly lower than that of 1 and any related analog, without exerting significant toxicity against normal blood cells. Preliminary studies showed that 2b follows different SAR rules as compared to the naphthoquinones. Among the series of synthesized epoxides, 2b was the most active one and was thus, after biotinylation, subjected to mass spectrometry-based affinity capture experiments aiming at the identification of target proteins. The MS data revealed 2b to address proteins that are associated with stress regulation processes which are critical for multiple myeloma cell survival.     

A theoretical study of angiotensin-converting enzyme inhibitors

Summary INDO molecular orbital calculations are reported for 35 selected angiotensin-converting enzyme inhibitors. QSARs are developed between pI₅₀ data and molecular electronic indices. The QSARs obtained reflect the importance of both charge-charge interactions between inhibitor and receptor and of specific interactions between groups on the inhibitor with points around the molecule which are postulated to correspond to binding sites at the receptor.     

Comparison of several models for multi-size bubbly flows on an adiabatic experiment

This paper deals with the modelling and numerical simulation of isothermal bubbly flows with multi-size bubbles. The study of isothermal bubbly flows without phase change is a first step towards the more general study of boiling bubbly flows. Here, we are interested in taking into account the features of such isothermal flow associated to the multiple sizes of the different bubbles simultaneously present inside the flow. With this aim, several approaches have been developed. In this paper, two of these approaches are described and their results are compared to experimental data, as well as to those of an older approach assuming a single average size of bubbles. These two approaches are (i) the moment density approach for which two different expressions for the bubble diameter distribution function are proposed and (ii) the multi-field approach. All the models are implemented into the NEPTUNE_CFD code and are compared to a test performed on the MTLOOP facility. These comparisons show their respective merits and shortcomings in their available state of development.     

Sonic spray ionization interface for liquid chromatography-mass spectrometry

A sonic spray ionization (SSI) interface for liquid chromatography-mass spectrometry (LC-MS) analysis was optimized for analysis of 2-[(1R)-3-[bis(1-methylethyl)amino]-1-phenylpropyl]-4-methyl-phenol (tolterodine), used as a model drug substance, and the influence of different parameter settings was evaluated using factorial design. A comparison between SSI and electrospray ionization (ESI) was made for tolterodine, tolterodine metabolites, and a set of steroids.SSI was found to give slightly poorer repeatability and broader peaks for tolterodine compared to ESI. However, there was no significant difference in chromatographic peak shape, and the repeatability using SSI was similar to that obtained using ESI if a ratio (area of tolterodine/area of metabolite) was used. In this study, the sensitivity was higher using SSI. For the analysis of pregnanolone, less water loss was obtained using SSI, probably due to less energy being transferred to the analyte upon ionization.     

Structure and hydration of polycytidylic acid from the data of infrared spectroscopy, EHF dielectrometry and computer modeling

The aim of this paper is to summarize the original results concerned with the elucidation of the role of water environment in the formation of different structures of polyribocytidylic acid (poly(rC)), depending on the pH, temperature and ion content. To solve this problem, we studied the hydration of poly(rC)-K⁺ in films differing in water content, by methods of infrared spectroscopy and piezogravimetry, and in solution, using the dielectric measurements at a wavelength of 7.6 mm (extremely high frequencies — EHF). The experimental results were confirmed by a Monte Carlo simulation of the interaction between water molecules and single-strand and double-strand poly(rC) fragments in clusters of 800 water molecules. A model of hydration of double-strand complex of poly(rC)⁺-poly(rC) has been proposed based on our results and the known X-ray parameters of the complex. The obtained results and proposed structure of poly(rC)⁺-poly(rC) suggest that, the stabilization of this complex occurs due to intra- and inter-chain water bridges, together with the hydrogen bonds between neutral and protonated cytosines in pairs.     

Nature of Alkali- and Coinage-Metal Bonds versus Hydrogen Bonds

We have quantum chemically studied the structure and nature of alkali- and coinage-metal bonds (M-bonds) versus that of hydrogen bonds between A−M and B⁻ in archetypal [A−M⋅⋅⋅B]⁻ model systems (A, B=F, Cl and M=H, Li, Na, Cu, Ag, Au), using relativistic density functional theory at ZORA-BP86-D3/TZ2P. We find that coinage-metal bonds are stronger than alkali-metal bonds which are stronger than the corresponding hydrogen bonds. Our main purpose is to understand how and why the structure, stability and nature of such bonds are affected if the monovalent central atom H of hydrogen bonds is replaced by an isoelectronic alkali- or coinage-metal atom. To this end, we have analyzed the bonds between A−M and B⁻ using the activation strain model, quantitative Kohn-Sham molecular orbital (MO) theory, energy decomposition analysis (EDA), and Voronoi deformation density (VDD) analysis of the charge distribution.     

木质素及其模型化合物的加氢脱氧反应研究进展

随着化石能源的不断枯竭,以及所产生的环境问题-温室效应及其高硫含量引起的酸雨,迫使人类寻找新型替代能源.在众多可再生能源中,生物质因其碳中性,易获取,作为唯一可转化为液体燃料的可再生资源,正日益受到重视.全球每年生物质产出高达1.7×1011t,其中,含75%的碳水化合物如纤维素、甲壳素和淀粉,20%木质素,其他占     

Comparison of the effective core potential and model potential methods in studies of electron correlation energy in molecules: Dihalides and halogen hydrides

Summary The effective core potential and model potential methods were used in post-SCF calculations on HC1, HBr, Cl₂, and Br₂ in order to gain insight into the effect of insufficient representation of inner nodes in the valence orbitals of the approximate methods. The results show that while the correlation energy may be slightly overestimated (by 1–7%), both the electric moment functions and the quantities depending on energy differences are consistently similar for the methods studied and close to the results from all-electron calculations.Dedicated to Prof. Klaus Ruedenberg     

Screening of Cerebrospinal Fluid and Blood Sera of Multiple Sclerosis Patients for Oligoclonal Immunoglobulins by Capillary Electrophoresis

Summary Multiple sclerosis (MS) is an autoimmune disease characterized by the production of specific types of immunoglobulins into the central nervous system. These immunoglobulins appear as oligoclonal bands (OCBs) in agarose isoelectric focusing (IEF) of cerebrospinal fluid (CSF). Among the cases with clinically definite MS, up to 95% have oligoclonal IgG bands in their CSF. In this report, we describe a micellar electrokinetic capillary chromatography (MEKC) method for the separation of CSF and serum proteins. MEKC was performed using 25 mM borate buffer, pH 10, containing 25 mM SDS at 20 kV and normal polarity. High values of repeatability in migration times and of reproducibility in peak areas were obtained (R.S.D. values were less than 2%). Calibration graphs were linear up to 2000 mg L^–1. LOQ was 6.5 mg L^–1 and LOD determined as a signal to noise ration of 3:1 was 4.5 mg L^–1. Analysis of CSF and serum samples from patients with clinical definite MS and healthy individuals demonstrated the presence of two peaks migrating as -globulins in the CSF samples of patients. These peaks were absent from controls and the serum of the same patients. Correlation of the data obtained from IEF and MEKC analysis for 25 patients showed that the diagnostic sensitivity and specificity of MEKC were ca 89% and 92% respectively. The obtained results indicate that this MEKC method may be helpful for the diagnosis of multiple sclerosis. Capillary electrophoresis compared to flat bed IEF provides reproducible results, requires shorter analysis time, and allows direct quantitative determination.Presented at: International Symposium on Separation and Characterization of Natural and Synthetic Macromolecules, Amsterdam, TheNetherlands, February 5–7, 2003     

Measurement and calculation of gas compressibility factor for condensate gas and natural gas under pressure up to 116 MPa

The volumetric properties of two reservoir fluid samples collected from one condensate gas well and one natural gas well were measured under four groups of temperatures, respectively, with pressure up to 116 MPa. For the two samples examined, the experimental results show that the gas compressibility factor increases with the increase of pressure. But the influence of the temperature is related to the range of the experimental pressure. It approximately decreases with the increase of temperature when the pressure is larger than (45 to 50) MPa, while there is the opposite trend when the pressure is lower than (45 to 50) MPa. The dew point pressure was also determined for the condensate gas sample, which decreases with the increase of temperature. The capabilities of four empirical correlations and a thermodynamic model based on equation of state for describing gas compressibility factor of reservoir fluids under high pressure were investigated. The comparison results show that the thermodynamic model recommended is the most suitable for fluids whatever produced from high-pressure reservoirs or conventional mild-pressure reservoirs.