Photocrosslinking of poly(2,3-epithiopropyl methacrylate) by the oxidation of pendant episulfide groups

In the photocrosslinking of poly(2,3-epithiopropyl methacrylate) (PETMA) films the effect of the pendant episulfide group's oxidation on the crosslinking of PETMA was investigated. Thermal crosslinking of PETMA is promoted by peroxides such as benzoyl peroxide and hydrogen peroxide. IR spectrum of the crosslinked PETMA showed that the reaction proceeded through the oxidation of episulfide groups by the peroxides. The anthracene (An) sensitized photocrosslinking of PETMA films also proceeded via the oxidation of episulfide groups by singlet oxygen. It was found that residual tetrahydrofuran (THF) in the films remarkably increased the rate of the photocrosslinking and/or reduced the induction period. From the further investigation concerning casting solvents it was found that residual CS₂, CCl₄, and CHCl₃ in films increased the rate of the photocrosslinking and/or reduced the induction period of the photocrosslinking. The disappearance rate of An in the films was also increased by the presence of residual CS₂, CCl₄, and CHCl₃, differring from the result of THF. These results were explained by a difference in lifetime of singlet oxygen in the films. From the results were explained by a difference in lifetime of singlet oxygen in the films. From the results concerning the effects of hydroperoxides such as THF hydroperoxide and t-butyl hydroperoxide on the photocrosslinking of PETMA films the acceleration effect of the residual THF was deduced to be due to the promotion of singlet oxygen-oxidation of sulfide groups by protic compounds such as THF hydroperoxide and H₂O in the THF.     

Determination of S-carboxymethyl-L-cysteine and some of its metabolites in urine and serum by high-performance liquid chromatography using fluorescent pre-column labelling.

Pre-column labelling techniques are described for the determination of S-carboxymethyl-L-cysteine (CMC) and its metabolites in urine and plasma samples by high-performance liquid chromatography (HPLC) without prior extraction. All substances containing an amino group were converted into fluorescent fluorenylmethyl derivatives with 9-fluorenylmethyloxycarbonyl chloride (FMOC). Deaminated or N-acetylated carbocysteine metabolites were coupled with 1-pyrenyldiazomethane (PDAM) to give fluorescent PDAM esters. Similar results were obtained with the two commercially available and stable diazomethane derivatives PDAM and 9-anthryldiazomethane (ADAM). Following double derivatization with PDAM and FMOC, in a single chromatographic run with two fluorescence detectors connected in series, amines and amino(carboxylic) acids could be detected by their FMOC residues and, simultaneously, carboxylic acids were detected as fluorescent PDAM esters. The (R) and (S) enantiomers of the sulphoxides of CMC, of methylcysteine and of N-acetyl CMC were separated, although the reversed-phase HPLC system did not contain a chiral additive or stationary phase designed for the separation of enantiomers. The methods do not include liquid extraction steps and can therefore be performed either manually or automatically using an HPLC autosampler. These methods were used for the investigation of a disputed pharmacogenetic polymorphism of S-oxidation of CMC in humans, which until now has most often been studied using paper chromatography. The described techniques were applied to the determination of CMC and its metabolites in human urine and plasma samples.     

Construction of 4D-QSAR Models for Use in the Design of Novel p38-MAPK Inhibitors

The p38-mitogen-activated protein kinase (p38-MAPK) plays a key role in lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) release during the inflammatory process, emerging as an attractive target for new anti-inflammatory agents. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis [Hopfinger et al., J. Am. Chem. Soc., 119 (1997) 10509] was applied to a series of 33 (a training set of 28 and a test set of 5) pyridinyl-imidazole and pyrimidinyl-imidazole inhibitors of p38-MAPK, with IC50 ranging from 0.11 to 2100 nM [Liverton et al., J. Med. Chem., 42 (1999) 2180]. Five thousand conformations of each analogue were sampled from a molecular dynamics simulation (MDS) during 50 ps at a constant temperature of 303 K. Each conformation was placed in a 2 angstroms grid cell lattice for each of three trial alignments. 4D-QSAR models were constructed by genetic algorithm (GA) optimization and partial least squares (PLS) fitting, and evaluated by leave-one-out cross-validation technique. In the best models, with three to six terms, the adjusted cross-validated squared correlation coefficients, Q2adj, ranged from 0.67 to 0.85. Model D (Q2adj = 0.84) was identified as the most robust model from alignment 1, and it is representative of the other best models. This model encompasses new molecular regions as containing pharmacophore sites, such as the amino-benzyl moiety of pyrimidine analogs and the N1-substituent in the imidazole ring. These regions of the ligands should be further explored to identify better anti-inflammatory inhibitors of p38-MAPK.     

Synchrotron radiation circular dichroism spectroscopy of ribose and deoxyribose sugars, adenosine, AMP and dAMP nucleotides.

Synchrotron radiation circular dichroism (SRCD) spectra of ribose and deoxyribose sugars, adenosine, AMP and dAMP nucleotides and cyclic derivatives were measured in the vacuum ultraviolet region (down to 168 nm for sugars and 175 nm for adenine derivatives) and at different pH values (3, 6-7, 9-10) and temperatures (between 5 and 45 degrees C). The information content in the VUV region is important since the CD bands strongly depend on the chemical structure of the sugar, the presence and orientation of a phosphate group and the protonation state of adenine. On the other hand, single or double deprotonation of the phosphoric acid group has no influence on the spectra. We assign the vacuum ultraviolet (VUV) CD bands of the nucleoside and nucleotides to be due mainly to n-->pi* transitions in the adenine nucleobase based on a comparison with the absorption spectra. The CD bands of the sugars are due to n(O -->sigma*) transitions and are much smaller than the CD signal from the nucleotides in the VUV region. Bands are assigned to both pyranose and open-chain forms.     

Electron transfer dissociation of peptide anions

Ion/ion reactions of multiply deprotonated peptide anions with xenon radical cations result in electron abstraction to generate charge-reduced peptide anions containing a free-radical site. Peptide backbone cleavage then occurs by hydrogen radical abstraction from a backbone amide N to facilitate cleavage of the adjacent C-C bond, thereby producing a- and x-type product ions. Introduction of free-radical sites to multiply charged peptides allows access to new fragmentation pathways that are otherwise too costly (e. g., lowers activation energies). Further, ion/ion chemistry, namely electron transfer reactions, presents a rapid and efficient means of generating odd-electron multiply charged peptides; these reactions can be used for studying gas-phase chemistries and for peptide sequence analysis.     

Melting points and thermal expansivities of proton-disordered hexagonal ice with several model potentials

A method of free energy calculation is proposed, which enables to cover a wide range of pressure and temperature. The free energies of proton-disordered hexagonal ice (ice Ih) and liquid water are calculated for the TIP4P [J. Chem. Phys. 79, 926 (1983)] model and the TIP5P [J. Chem. Phys. 112, 8910 (2000)] model. From the calculated free energy curves, we determine the melting point of the proton-disordered hexagonal ice at 0.1 MPa (atmospheric pressure), 50 MPa, 100 MPa, and 200 MPa. The melting temperatures at atmospheric pressure for the TIP4P ice and the TIP5P ice are found to be about T(m)=229 K and T(m)=268 K, respectively. The melting temperatures decrease as the pressure is increased, a feature consistent with the pressure dependence of the melting point for realistic proton-disordered hexagonal ice. We also calculate the thermal expansivity of the model ices. Negative thermal expansivity is observed at the low temperature region for the TIP4P ice, but not for the TIP5P ice at the ambient pressure.     

A kinetic stability study of <Emphasis Type="Italic">M</Emphasis>N<Subscript>5</Subscript> (<Emphasis Type="Italic">M</Emphasis>=Li,Na, K,and Rb)

A structure and kinetic stability study on some complexes with the general formula MN₅, where M are the alkali-metal atoms, Li, Na, K, and Rb, has been carried by using hybrid density functional methods. Complex B (C_2v) with two points of attachment to the N₅ ring is the most energetically favored for all metals considered here. Pyramidal structures A (C_5v) are kinetically unstable and they rapidly rearrange to the most stable planar structures B. At the QCISD(T)/6-311 + G*//B3LYP/6-311 + G* + ZPE (B3LYP/6-311 + G*) level, the decomposition barrier heights of LiN₅-B, NaN₅–B, KN₅-B, and RbN₅-B are predicted to be 19.9, 22.0, 22.5, and 23.0 kcal/mol, respectively. In addition, the rate constants of the decomposition reaction MN₅-B MN₃ + N₂ (M + Li, Na, K, and Rb) are also predicted using conventional transition state theory and canonical variational transition state theory, respectively.     

The performance of density functional theory for LnF (Ln=Nd,Eu, Gd,Yb) and YbH

Different density functional theory (DFT) functionals have been evaluated by studying geometries and bond strengths of YbH, YbF, EuF, GdF, and NdF and compared with accurate CCSD(T) results and, when available, experiment. The agreement between the CCSD(T) results and experiment, when available, is good. The agreement is also good between bond strengths calculated at the DFT level using relativistic effective core potentials and the CCSD(T) results. However, the all-electron ADF calculations systematically overestimate binding energies. The geometries obtained by both the all-electron and the effective-core-potential-based DFT calculations are generally in good agreement with the CCSD(T) results.Contribution to the Björn Roos Honorary Issue     

Monolithic octadecylsilyl-silica gel column for the high-speed ion chromatographic determination of acidity

A monolithic ODS-silica gel column modified by saturating it with lithium dodecylsulfate (Li-DS) was used to demonstrate the high-speed separation of H+ from other mono- and divalent cations, such as Na+, NH4+, K+, Mg2+ and Ca2+ using ion chromatography (IC). Using a 5 mM EDTA-2K solution containing 0.10 mM Li-DS (pH 4.80) as eluent, H+ was eluted with a sharp and symmetrical peak within 1.0 min before other cations at a flow-rate of 1.5 ml min(-1). The rapid elution of H+ and its conductimetric detection could be attributed to the presence of EDTA (HY2-), which can convert H+ ions as anions. i.e. H(+) + H2Y(2-) --> H3Y(-). The acidity of rainwater and deionized water samples was determined using this IC system with satisfactory results.     

Substituent control in the diastereoselectivity of dipolar cycloadditions of nitrones and their Zn(II) complexes with N-arylmaleimides

The π-π stacking interactions between maleimide's and nitrone's aromatic rings during the 1,3-dipolar cycloaddition were assumed to control the exo-endo selectivity of the reaction. The exo-endo ratios change during the reactions until they reach a constant value, which depends on the substituent. Electron-withdrawing groups favour the exo adduct while electron-donating groups favour the endo adduct. The nitrone ZnBr₂ complexes react much more slowly than the free nitrone and the cycloaddition is exo selective in all cases independent of the substituents on the maleimide's aromatic ring. Thermal retrocycloaddition of the cycloadducts produce the corresponding nitrones. The ring opening in the presence of secondary amines did not induce imine formation. endo Adducts were shown for the first time to be the stable paramagnetic compounds.