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Studied Molecules (studied + molecule)
Selected AbstractsNuclear magnetic moments from NMR spectra,Experimental gas phase studies and nuclear shielding calculationsCONCEPTS IN MAGNETIC RESONANCE, Issue 5 2007Karol Jackowski Abstract NMR spectra of gaseous compounds and quantum chemical calculations are combined to determine new accurate values of magnetic dipole moments for a series of nuclei. We have analyzed shielding constants, resonance frequencies, and nuclear magnetic moments for a group of simple molecules. The chemical shifts and resonance frequencies are measured at 300 K and extrapolated to the zero-density limit in order to remove all the intermolecular effects from the experimental parameters. The absolute shielding constants in the studied molecules are obtained from ab initio calculations. Assuming the proton magnetic moment as the reference, we determine the nuclear magnetic moments of 13C, 14N, 15N, 17O, 19F, 29Si, 31P, 33S, and 73Ge. The new nuclear magnetic moments are consistent with the experimental NMR parameters, and using these new values one can for the first time predict successfully the shielding constant of a nucleus in a molecule when the corresponding resonance frequency is known. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 246,260, 2007. [source] Electrochemical, Chemical and Enzymatic Oxidations of PhenothiazinesELECTROANALYSIS, Issue 17 2005B. Blankert Abstract The oxidation of several phenothiazine drugs (phenothiazine, promethazine hydrochloride, promazine hydrochloride, trimeprazine hydrochloride and ethopropazine hydrochloride) has been carried out in aqueous acidic media by electrochemical, chemical and enzymatic methods. The chemical oxidation was performed in acetic acid with hydrogen peroxide or in formate buffers using persulfate. The enzymatic oxidation was performed in acetate or ammonium formate buffer by the enzyme horseradish peroxidase in the presence of H2O2. Molecules with, in the lateral chain, two carbon atoms (2C) separating the ring nitrogen and the terminal nitrogen, showed two parallel oxidation pathways, that is (i) formation of the corresponding sulfoxide and (ii) cleavage of the lateral chain with liberation of phenothiazine (PHZ) oxidized products (PHZ sulfoxide and PHZ quinone imine). Molecules with three carbon atoms (3C) separating the two nitrogens were oxidized to the corresponding sulfoxide. The chemical oxidation of all the studied molecules by hydrogen peroxide resulted in the corresponding sulfoxide with no break of the lateral chain. Oxidation by persulfate yielded, for the 3C derivatives, only the corresponding sulfoxide, but it produced cleavage of the lateral chain for the 2C derivatives. The origin of the distinct oxidation pattern between 2C and 3C molecules might be related to steric effects due to the lateral chain. The data are of interest in drug metabolism studies, especially for the early search. In the case of 2C phenothiazines, the results predict the possibility of an in vivo cleavage of the lateral chain with liberation of phenothiazine oxidized products which are known to produce several adverse side effects. [source] String Fit: a new structurally oriented X-ray and neutron reflectivity evaluation techniqueJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3 2001Erich Politsch A novel method for the analysis of neutron and X-ray reflectivity measurements is presented. In contrast to existing methods, the new data fitting approach is structurally oriented and therefore only requires information about the chemical structure of studied molecules and no other ad hoc assumptions. Apart from the inversion of reflectivity into scattering length density profile, the inversion of scattering length density profile into molecular arrangement is addressed systematically for non-trivial molecular conformations for the first time. This includes the calculation of structural characteristics, such as radius of gyration or chain order parameters, based on measured reflectograms. Another important option is the possibility to evaluate simultaneously neutron and X-ray reflectograms of a given sample. For better convergence, especially for complex simultaneous evaluations, an effective extension of the normally used least-squares deviation function is introduced. Different simulated molecular ensembles are used to illustrate the features of the new approach; typically, excellent agreement between the simulated starting and final deduced data sets is achieved. [source] Evaluation of the reduction of imidazophenazine dye derivatives under fast-atom-bombardment mass-spectrometric conditions,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2006Marina V. Kosevich Abstract Satellite [M + 2]+, and [M + 3]+ peaks accompanying the common peak of the protonated molecule [M + H]+ that are known to indicate the occurrence of a reduction process were observed in the fast atom bombardment (FAB) mass spectra of imidazophenazine dye derivatives in glycerol matrix. The distribution of the abundances in the [M + nH]+ peak group varied noticeably for different derivatives. This indicated different levels of the reduction depending on the different structure variations of the studied molecules. In the search for correlations between the mass spectral pattern and the structural features of the dyes, ab initio HF/6-31++G** quantum chemical calculations were performed. They revealed that the abundances of the [M + 2]+, and [M + 3]+ ions show growth proportional to the decrease of the energy of the lowest unoccupied molecular orbital, i.e. proportional to the increase of the electron affinity of the dye molecule. A method for rapid screening of reductive properties of sets of dye derivatives on the basis of the FAB mass spectral data is discussed. Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis, pharmacology, crystal properties, and quantitative solvation studies from a drug transport perspective for three new 1,2,4-thiadiazolesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010German L. Perlovich Abstract A novel 1,2,4-thiadiazoles were synthesized. Crystal structures of these compounds were solved by X-ray diffraction experiments and comparative analysis of molecular conformational states, packing architecture, and hydrogen bonds networks were carried out. Thermodynamic aspects of sublimation processes of studied compounds were determined using temperature dependencies of vapor pressure. Thermophysical characteristics of the molecular crystals were obtained and compared with the sublimation and structural parameters. Solubility and solvation processes of 1,2,4-thiadiazoles in buffer, n -hexane and n -octanol were studied within the wide range of temperature intervals and thermodynamic functions were calculated. Specific and nonspecific interactions of molecules resolved in crystals and solvents were estimated and compared. Distribution processes of compounds in buffer/n -octanol and buffer/n -hexane systems (describing different types of membranes) were investigated. Analysis of transfer processes of studied molecules from the buffer to n -octanol/n -hexane phases was carried out by the diagram method with evaluation of the enthalpic and entropic terms. This approach allows us to design drug molecules with optimal passive transport properties. Calcium-blocking properties of the substances were evaluated. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3754,3768, 2010 [source] DFT-GIAO1H NMR chemical shifts prediction for the spectral assignment and conformational analysis of the anticholinergic drugs (,)-scopolamine and (,)-hyoscyamineMAGNETIC RESONANCE IN CHEMISTRY, Issue 6 2010Marcelo A. Muñoz Abstract The relatively large chemical shift differences observed in the 1H NMR spectra of the anticholinergic drugs (,)-scopolamine 1 and (,)-hyoscyamine 2 measured in CDCl3 are explained using a combination of systematic/molecular mechanics force field (MMFF) conformational searches and gas-phase density functional theory (DFT) single point calculations, geometry optimizations and chemical shift calculations within the gauge including/invariant atomic orbital (GIAO) approximation. These calculations show that both molecules prefer a compact conformation in which the phenyl ring of the tropic ester is positioned under the tropane bicycle, clearly suggesting that the chemical shift differences are produced by the anisotropic effect of the aromatic ring. As the calculations fairly well predict these experimental differences, diastereotopic NMR signal assignments for the two studied molecules are proposed. In addition, a cursory inspection of the published 1H and 13C NMR spectra of different forms of 1 and 2 in solution reveals that most of them show these diastereotopic chemical shift differences, strongly suggesting a preference for the compact conformation quite independent of the organic or aqueous nature of the solvent. Copyright © 2010 John Wiley & Sons, Ltd. [source] Porous silicon surfaces for metabonomics: Detection and identification of nucleotides without matrix interferencePHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 6 2007D. Gómez Abstract In present work, porous silicon surfaces (PSS) have been developed for time of flight mass spectrometric experiments (TOF-MS) in the monitoring of nucleotides, commonly found as metabolites in the cell. The mass range of the studied molecules (, 400 amu) is common to several important messengers and other metabolites. Different porosified surfaces have been developed by means of electrochemical etching and different degree of porosity and pore size achieved as function of silicon dopant concentration, silicon resistivity, current density and the presence or absence of illumination along the process. As main conclusion, it can be said that an interesting commercial nucleotide (Cyclic adenosine monophosphate, c-AMP) has been detected on low concentrations (,hundreds of femtomols) for some of the fabricated porous surfaces. Taking into account that these concentrations are similar to the ones found in real samples, this result opens the possibility to the fabrication of DIOS (Desorption Ionization On Silicon) chips for the detection of nucleotides in biological fluids. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Up-regulation of pro-inflammatory genes as adaptation to hypoxia in MCF-7 cells and in human mammary invasive carcinoma microenvironmentCANCER SCIENCE, Issue 4 2010Marco Tafani The role of tumor cells in synthesizing pro-inflammatory molecules is still controversial. Here we report that hypoxic treatment of the MCF-7 human mammary adenocarcinoma cell line induced activation of hypoxia-inducible factor 1, (HIF-1,) and nuclear factor-kappa B (NF-,B). Importantly, hypoxia regulated expression of alarmin receptors such as the receptor for advanced glycation end products (RAGE) and the purinoreceptor (P2X7R), and up-regulated inflammatory response (IR) genes such as the inducible enzymes nitric oxide synthase (NOS2), cycloxygenase (COX2), and the acute-phase protein pentraxin-3 (PTX3). Hypoxia also stimulated chemokine (C-X-C motif) receptor 4 (CXCR4) mRNA synthesis. In fact, the CXCR4 ligand stromal-derived factor-1, (SDF-1,) increased invasion and migration of hypoxic MCF-7 cells. Inhibition of HIF-1, by chetomin and NF-,B by parthenolide reduced mRNA and protein expression of the studied molecules and prevented invasion of hypoxic MCF-7 cells. Moreover, solid invasive mammary tumor microenvironment was analyzed after laser-capture microdissection (LCMD) comparing tumor versus host normal tissue. Nuclear translocation of HIF-1, and NF-,B and up-regulation of IR, CXCR4, estrogen receptor , (ER,), and epithelial growth factor receptor (EGFR) was observed in tumor but not in host normal tissue in the absence of a local inflammatory leukocyte infiltrate. We conclude that under hypoxic conditions MCF-7 cells acquire a pro-inflammatory phenotype, and that solid human mammary carcinoma evidenced a similar activation of HIF-1,, NF-,B, and IR genes in malignant tumor cells as compared to the normal host tissues. We suggest a role for IR activation in the malignant progression of transformed cells. (Cancer Sci 2010; 101: 1014,1023) [source] | |||||||||||||