A microwave-assisted click chemistry synthesis of 1,4-disubstituted 1,2,3-triazoles via a copper(I)-catalyzed three-component reaction

A microwave-assisted three-component reaction was used to prepare a series of 1,4-disubstituted-1,2,3-triazoles from corresponding alkyl halides, sodium azide, and alkynes. This procedure eliminates the need to handle organic azides, as they are generated in situ, making this already powerful click process even more user-friendly and safe.     

Carbon nanohorns grown from ruthenium nanoparticles

A nanoscale ruthenium/gold bimetallic cluster of clusters has been used as a molecular precursor to produce pure ruthenium nanoparticles (seeds) as catalysts for the growth of carbon nanohorns (CNHs).     

Water adsorption and hydrolysis on molecular transition metal oxides and oxyhydroxides

Addition of water to molecular transition metal oxides (TiO2(g) and CrO3(g)) and oxyhydroxides (ScO(OH)(g), VO2(OH)(g), and MnO3(OH)(g)) was studied by means of quantum chemistry. In the investigated reactions, each reaction step comprised the breaking of one M=O bond and the formation of two OH groups. Exothermicity was observed when the product had tetrahedral or lower oxygen coordination. The reactions were found to involve stable water complexes as intermediates. The stabilities of such complexes were accentuated in the addition reaction Sc(OH)3(g) + H2O(g), in which the formation of a tetrahedral complex was found exothermic. For VO(OH)3(g), CrO2(OH)2(g), and MnO3(OH)(g), water addition to the remaining M=O bonds was found endothermic, whereas the formation of water complexes, using hydrogen bonds and preserving the oxyhydroxide kernel, was preferred. Thus, the sequence of such kernels for water clustering in the investigated reactions was found to be Sc(OH)3.H2O(g), Ti(OH)4(g), VO(OH)3(g), CrO2(OH)2(g), and MnO3(OH)(g). These stability considerations are important, as CrO2(OH)2(g) is believed to be the product of water-induced degradation of the protective chromium oxide scale on stainless steel at elevated temperatures.     

Synthesis and biological activity of novel epothilone aziridines

[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones.     

High-performance liquid chromatographic analysis of biogenic amines in biological materials as o-phthalaldehyde derivatives.

A remarkably sensitive, simple and selective reversed-phase high-performance liquid chromatographic (HPLC) method has been developed, allowing, for the first time, the direct measurement of histamine, norepinephrine, octopamine, normetanephrine, dopamine, serotonin and tyramine in a single sample of plasma (2 ml), tissue (0.2 g), or urine. The biogenic amines were modified by pre-column derivatization with o-phthalaldehyde which stabilizes the molecules, aids in extraction, and improves HPLC detection at the nanogram level. To minimize losses during the sampling procedure a careful collection procedure was designed. We developed a simple sample cleanup in which the samples were thawed, neutralized with KOH, immediately derivatized, extracted into ethyl acetate (EtOAc) and then chromatographed by HPLC. The derivatives were stable in EtOAc for more then 24 h. Interfering amino acids were removed from the EtOAc by partitioning twice with Na2HPO4 buffer (pH 10.0). Complete separation was achieved in ca. 60--90 min on a muBondapak phenyl column using a stepwise gradient of acetonitrile and/or methanol-phosphate buffer (pH 5.1). A variable wavelength fluorometer with a 5-microliter flow-cell was used (excitation 340 nm; emission 480 nm). Linearity ranged from 200 pg to 50 ng onto the column. Precision (R.S.D.) for retention times was 1% and for derivatization and injection 2.5%. Recoveries of the seven biogenic amines from plasma spiked with 25 ng/ml averaged 70%, with a relative standard deviation of 6%. Separation studies were also done using a muBondapak C18 column. The effects of various eluents are presented. Gas-liquid chromatography was also investigated but lacked the sensitivity achieved by HPLC. The HPLC method is used routinely for the determination of biogenic amines in plasma from pigs with malignant hyperthemia and thermally stressed bovine. Significant differences in levels of biogenic amines were noted between stressed and non-stressed animals. Data on rat brain tissue samples were compared with the trihydroxyindole method and canine heart tissue was analyzed for ventricular norepinephrine and dopamine. Application of the method to urine from normal persons and a patient with a brain tumor has been demonstrated.     

Synthesis of N-1-(Indanyloxymethyl) and N-1-(4-Hydroxybut-2-enyloxymethyl) Analogues of the HIV Drugs Emivirine and GCA-186

A series of Emivirine and GCA-186 analogues substituted at N-1 with indan-1-yloxymethyl (6a–6c) and indan-2-yloxymethyl (6d–6f) were synthesized by reaction of the corresponding bis(indanyloxy)methans with uracils having 5-ethyl or 5-isopropyl and 6-benzyl or 6-(3,5-dimethylbenzyl) substituents. A route to the corresponding N-1 substituted 4-hydroxybut-2-enyloxymethyl analogue was also devised. All newly synthesized compounds showed potent activity against wild-type HIV-1, the most active compound being 5-ethyl-1-(indan-1-yloxymethyl)-6-(3,5-dimethylbenzyl)uracil (6b), which was 50-fold more active than Emivirine.     

Predissociation spectroscopy of the argon-solvated H5O2+ "zundel" cation in the 1000-1900 cm(-1) region

Predissociation spectra of the H5O2+.Ar(1,2) cluster ions are reported in the 1000-1900 cm(-1) region. The weakly bound argon atoms enable investigation of the complex in a linear action mode, and the resulting spectra are much simpler than those reported previously in this region [Asmis et al., Science 299, 1375 (2003) and Fridgen et al., J. Phys. Chem. A 108, 9008 (2004)], which were obtained using infrared multiphoton dissociation of the bare complex. The observed spectrum consists of two relatively narrow bands at 1080 and 1770 cm(-1) that are likely due to excitation of the shared proton and intramolecular bending vibrations of the two water molecules, respectively. The narrow linewidths and relatively small (60 cm(-1)) perturbation introduced by the addition of a second argon atom indicate that the basic "zundel" character of the H5O2+ ion survives upon complexation.     

Vesicle adsorption and lipid bilayer formation on glass studied by atomic force microscopy

The adsorption of phosphatidylcholine (PC) vesicles (30, 50, and 100 nm nominal diameters) and of dye-labeled PC vesicles (labeled with 6% Texas Red fluorophore (TR) and encapsulated carboxy fluorescein (CF)) to glass surfaces was studied by contact mode atomic force microscopy in aqueous buffer. These studies were performed in part to unravel details of the previously observed isolated rupture of dye-labeled PC vesicles on glass (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), specifically to differentiate partial rupture, that is, pore formation and leakage of entrapped dye, from full rupture to form bilayer disks. In addition, the adhesion potential of PC vesicles on glass was calculated based upon the adhesion-driven flattening of adsorbed vesicles and a newly developed theoretical model. The vesicles were found to flatten considerably upon adsorption to glass (width-to-height ratio of approximately 5), which leads to an estimate for the adhesion potential and for the critical rupture radius of 1.5 x 10(-4) J/m2 and 250 nm, respectively. Independent of vesicle size and loading with dye molecules, the adsorption of intact vesicles was observed at all concentrations below a threshold concentration, above which the formation of smooth lipid bilayers occurred. In conjunction with previous work (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), these data show that 6% TR 20 mM CF vesicles adsorb to the surface intact but undergo partial rupture in which they exchange content with the external buffer.     

New colorimetric and fluorimetric methods for the determination of 1,4-cyclohexanedione

1,4-Cyclohexanedione has been determined by reaction with o-phthalaldehyde in sulfuric acid. The determinations depend on the formation of a dicationic salt of pentacenequinone. A sensitive and highly selective fluorimetric method is recommended, but the reaction can also be used spectrophotometrically. Many organic compounds, as well as the isomers of 1,4-cyclohexanedione, give negative results. A spot test is described which can be used for quick preliminary investigations of complex mixtures for I,4-cyclohexanedione.     

Effect of bending and torsion rigidity on self-diffusion in polymer melts: a molecular-dynamics study

Extensive molecular-dynamics simulations have been performed to study the effect of chain conformational rigidity, controlled by bending and torsion potentials, on self-diffusion in polymer melts. The polymer model employs a novel torsion potential that avoids computational singularities without the need to impose rigid constraints on the bending angles. Two power laws are traditionally used to characterize the dependence of the self-diffusion coefficient on polymer length: D proportional to N(-nu) with nu=1 for NNe (reptation regime), Ne being the entanglement length. Our simulations, at constant temperature and density, up to N=250 reveal that, as the chain rigidity increases, the exponent nu gradually increases towards nu=2.0 for NNe. The value of Ne is slightly increased from 70 for flexible chains, up to the point where the crossover becomes undefined. This behavior is confirmed also by an analysis of the bead mean-square displacement. Subsequent investigations of the Rouse modes, dynamical structure factor, and chain trajectories indicate that the pre-reptation regime, for short stiff chains, is a modified Rouse regime rather than reptation.