Does Perdeuteration Increase the Polarity of Janus Face Cycloalkanes?

Stimulated by a suggestion of the late Professor Jack D. Dunitz, that perdeuterated Janus face cycloalkanes may be more polar than their unlabelled forms, the deuterated isotopologue of all cis-1,2,3,4,5,6-hexafluorocyclohexane ([²H₆]- 1a ) and all cis-1,2,3,4-tetrafluorocyclopentane ([²H₆]- 3a ) were prepared. Computation at the B3LYP−D3 level indicated that [²H₆]- 1a is not more polar than its protio form 1, however perdeuterated cyclopentane [²H₆]- 3a may indeed be more polar than 3 , although the magnitude is predicted to be small. None-the-less retention time analysis on a reverse phase GC/MS column of an add-mix of 3 and [²H₆]- 3a gave some indication that the per-deuterated isotopologue 3a was detected marginally before the unlabelled compound consistent with increased polarity associated with perdeuteration.     

On the search for non-electrochemical cold fusion: Production of D2 off of high surface area Pd colloid

The reaction of Et₃SiD with Na₂PdCl₄ in CD₃OD was carried out under conditions where we monitored for production of neutrons and/or -rays. This reaction produces D₂ off the surface of Pd colloid. The formation of high surface area Pd metal was confirmed by transmission electron microscopy /TEM/. The heat from the all protio control reaction and the all protio control reaction and the all deutero reaction was monitored and found to be the same within the limits of these experiments. Within the limits of our neutron and gamma detection, we conclude that no measurable fusion occurred during this reaction.     

Effects of deuteration on the structure and magnetic properties of bis-quinolinium tetrabromidocuprate(II) dihydrate

Abstract

The partially [d₆, 2] and fully [d₂₀, 3] deuterated analogues of (QuinH)₂CuBr₄·2H₂O (d₀, 1) were prepared and their crystal structures were determined [Quin = quinoline]. In both compounds, there is a clear disorder in the positions of the bromide ions which was resolved. This led to a reexamination of the structure of the parent, fully protonated compound (1) where a small percentage of previously unrecognized disorder was also observed and the structure rerefined. Variable temperature magnetization measurements over the range 1.8–310?K indicate that all three materials behave as magnetically well-isolated layers that can be evaluated using the 2D-quantum Heisenberg antiferromagnetic model. Final fitting results for the partially (J = ?5.96(5) K) and fully (J = ?5.77(2) K) deuterated compounds indicate slightly weaker exchange compared to the protonated compound (J = ?6.17(3) K), likely as a result of the increased disorder in the deuterated phases.     

Chromatographic performance of deuterated solvents in reversed phase micro high performance liquid chromatography

The chromatographic performance of the deuterated solvents, CD₃OD and D₂O, has been investigated in reversed-phase micro high performance liquid chromatography. The chromatographic performance of CD₃OD is only slightly superior to that of CH₃OH. However, the performance of D₂ is significantly superior to that of H₂O, separation of aromatics being improved by about 30%. D₂ is a particularly powerful solvent for the separation iof deuterated and non-deuterated compounds.     

Comparison of Column Packings for Isocratic High-Performance Liquid Chromatographic Analysis of Carotenoids Using Non-Aqueous Reversed-Phase

Abstract

Ten different columns are compared for the isocratic non-aqueous reversed-phase separation of carotenoids, using solvent mixtures of ethyl acetate-acetonitrile both with and without 0.1% n-decanol as modifier. Conditions were established for separation of a mixture of alfalfa carotenoids containing mainly neoxanthin, violaxanthin, lutein and β-carotene. The best material for use for rapid isocratic separation of all major components was a high carbon loading non-endcapped material with ODS functionality, although one endcapped C8 material gave similar results. The use of n-decanol as mobile phase modifier is imperative to rapidly condition new columns to give optimum peak shape and definition and system linearity.     

Solubility of thioindigo dopants in a smectic liquid crystal host evaluated by 2H NMR spectroscopy

The solubility of two partially deuterated thioindigo dopants in a smectic liquid crystal host was evaluated by variable temperature ²H NMR spectroscopy and polarized microscopy. 2H NMR spectra showed that the dopant (±)-6,6'-bis(2-octyloxy)-5,5-dinitrothioindigo-d ₆ forms a homogeneous solution with the smectic phases of the liquid crystal host (±)-4-(4-methylhexyloxy)phenyl 4-decyloxybenzoate (PhB) up to its saturation point of 3 mol %. These results are consistent with polarized microscopy observations of the dopant crystallizing out of solution upon reaching a concentration of 3 mol %. On the other hand, ²H NMR spectra of (±)-5,5'-dichloro-6,6'-bis(2-octyloxy)thioindigo-d ₆ dissolved in PhB showed evidence of a partitioning of the solution between smectic and isotropic microdomains, which increases with increasing dopant concentration—from 1.2 to 9.1 mol %. To a large extent, this smectic/isotropic microphase separation could not be detected by polarized microscopy. These results suggest that ²H NMR spectroscopy can provide a more accurate determination of the occurrence and extent of microphase separation in doped liquid crystal samples.     

Deuterated Solvents as Mobile Phase in Micro-HPLC

Abstract

The chromatographic performance of deuterated solvents, heavy water and deuteriobenzene, has been investigated in reversed phase and normal phase micro-HPLC. The performance of heavy water in separation was comparable or superior to that of light water in reversed phase mode. A slight improvement was also observed in catecholamines separation with heavy water. The performance of deuteriobenzene was observed as complicated in metal complexes separation, but a little difference was present. From those results, the combinations of micro HPLC and IR via flow-cell technique, proton-NMR, and ICP could be accomplished free from absorption or signals from mobile phase solvents.     

Mass spectrometry of methyltetrazoles

The mass spectra of tetrazole, all isomers of monomethyl- and dimethyltetrazole, several trifluoromethyl substituted tetrazoles, as well as deuterated analogs, were recorded. Loss of N₂ was the important fragmentation of the molecular ions of tetrazole and 2-methyl substituted tetrazoles; however, HN₂ loss was more important for 1-methyl substituted tetrazoles. The 1-methyl-tetrazoles showed molecular ion peaks while the 2-methyltetrazoles exhibited an unprecedented [M + 1] peak with no molecular ion.     

Ethylene polymerization reactions with Ziegler–Natta catalysts. II. Ethylene polymerization reactions in the presence of deuterium

Ethylene polymerization reactions with many Ziegler–Natta catalysts exhibit several features which differentiate them from polymerization reactions of α-olefins: a relatively low ethylene reactivity, higher polymerization rates in the presence of α-olefins, a high reaction order with respect to ethylene concentration, and strong reversible rate depression in the presence of hydrogen. A detailed kinetic analysis of ethylene polymerization reactions (see ref. 1 ) provided the basis for a new reaction scheme which explains all these features by postulating the equilibrium formation of a Ti C₂H₅ species with the H atom in the methyl group β-agostically coordinated to the Ti atom in an active center. This mechanism predicts that the β-agostically stabilized Ti C₂H₅ groups can decompose in the β-hydride elimination reaction with expulsion of ethylene and the formation of a Ti H bond even in the absence of hydrogen in the reaction medium. If D₂ is used as a chain transfer agent instead of H₂, the mechanism predicts the formation of deuterated ethylene molecules, which copolymerize with protioethylene. To prove this prediction, several ethylene homopolymerization reactions were carried out with a supported Ziegler–Natta titanium-based catalyst in the presence of large amounts of D₂. Analysis of gaseous reaction products and polymers confirmed the formation of several types of deuterated ethylene molecules and protio/deuterioethylene copolymers, respectively. In contrast, a metallocene catalyst, Cp₂ZrCl₂ MAO, does not exhibit these kinetic features. In the presence of deuterium, it produces only DCH₂ CH₂ (CH₂ CH₂)_x CH₂ CH₂D molecules. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4273–4280, 1999     

Class Fractionation of Acidic Glycolipids and Further Separation of Gangliosides by OPTLC

Abstract

The use of the OPTLC method has been extended to the separation of the acidic fraction of the total lipid extract derived from a given blood element. This newly developed method is suitable for the interclass separation of sulphatides and gangliosides and further intraclass separation of gangliosides on the same TLC plate with step gradient development. The elutions can be performed on 10 × 10 cm (or larger) HPTLC plates with 13 parallels on each one. The chromatograms were stained either with orcinol-H₂SO₄ to show class separation (in this case only a single isocratic elution was performed) or with rescrcinol-HCl reagent to visualize the ganglioside intraclass separation. The chromatograms were evaluated by spectrodensitometric scanning and the reproducibility of the separation was determined.     

Determination of N-Nitrosonornicotine in Tobacco by Gas Chromatography/Mass Spectroscopy

Abstract

N-Nitrosonornicotine has been determined in tobacco products. Quantitation was accomplished by GC/MS operated in the chemical ionization mode with selected-ion recording of N-nitrosonornicotine and the deuterated internal standard, N-nitrosonornicotine-d₄. Levels ranging from 0.7 to 26 mcg/gm were found.     

Electron-impact induced fragmentation of 2-substituted 2H-cyclopenta[D]pyridazines

The mass spectra of the non-benzenoid aromatic heterocycles 2H- and 2-methyl-2H-cyclopenta[d]pyridazine and several deuterated analogs have been analyzed. The majority of the nitrogen lost from these heterocycles occurs as HCN OR H₂CN. The deuterium labeling suggests a rearrangement of the molecular ion prior to fragmentation.     

Enhanced Recognition of Spin Trapped Radicals In Complex Mixtures: Deuterated Nitronyl Adducts Provide A Gas Chromatographic/Mass Spectrometric Marker

Abstract

The use of deuterated analogues of α-phenyl-N-tert-butyl nitrone (PBN) are reported for GC/MS analysis of spin trapping products. PBN-d₉ and PBN-d₄₁, deuterated in the tert-butyl group (the latter also deuterated in the phenyl ring), result in a more diagnostic fragment ion, C₄D₉ ⁺ (m/z = 66) which improves the recognition of PBN adducts in mixtures. This feature has helped identify a new 1,3-radical addition product of PBN-d₉ formed during azobis(isobutyronitrile) thermolysis (addition of 2-cyano-2-propyloxyl followed by 2-cyano-2-propyl radicals). the ¹³C-trichloromethyl radical adduct of PBN-d₁₄ produced during ¹³C-carbon tetrachloride incubation with rat liver micrcsomes was identified by GC/MS in a complicated biological extract mixture.     

Separation of Ethyl Anthranilate Azopigments from Germ-Free Rat Feces by Reversedphase High-perform Ance Liquid Chromatography

Abstract

A simple method was developed for the separation of ethyl anthranilate azopigments derived from conjugated bilirubins prepared from germfree (GF) rat feces. The Δ and α₀ azopigments were separated and these two azopigments were also separated into their endo-vinyl- and exo-vinyl isomers, respectively. The reverse-phase, high-performance liquid chromatographic (HPLC) separation was achieved by using a μBondapak C₁₈ column and a mixture of acetonitrile, distilled water and sodium acetate as the mobile phase.     

SELECTIVE ALKYLATION/ACYLATION OF DI- OR TRIANIONS: EXPEDITIOUS DERIVATIZATION OF ENDOTHELIN ANTAGONISTS[1]

ABSTRACT

Sitaxsentan sodium (1, TBC11251Na) is an ET_A selective endothelin antagonist under clinical development for pulmonary arterial hypertension and congestive heart failure. Second generation compounds, as exemplified by TBC2576 (2) are currently under development in our laboratories. To rapidly access analogs of 1 and 2, a route was developed for the selective alkylation or acylation of the corresponding di- or trianions derived from these two highly functionalized compounds. We report here on this straightforward, yet effective, procedure consisting of treating the di- or trianions with an excess amount of electrophiles, followed by a rapid quench. In this manner, selective alkylation or acylation of 1 and 2 was achieved with satisfactory yields.     

Synthesis and anticancer activities of proline-containing cyclic peptides and their linear analogs and congeners

A solution phase method was adopted for the synthesis of proline-containing cyclic pentapeptide 2 and total synthesis of naturally occurring cyclic heptapeptide Reniochalistatin B 3. For the synthesis of 3, both divergent and convergent strategies were used to improve the overall yield from 12 to 25%. Different N and C terminal modified linear analogs and congeners of 2 and 3 were synthesized. Both cyclic peptides 2 and 3 and their linear analogs/congeners were evaluated for anti-cancer activity against HeLa cell line, among which pentapeptide 2?h and hexapeptide 3n with N-terminal protected hexafluoroisopropyl carbamates (HFIPC) interestingly showed higher cytotoxicity with an IC₅₀ of 2.73 and 4.3?µM, respectively compared to their Boc-protected analogs 2a (IC₅₀ 20?µM) and 3c (IC₅₀ 38.51?µM) and cyclic peptides 2 (>100?µM) and 3 (47?µM). These results were further validated by biological experiments such as colony formation and wound healing assays.     

The kinetics of isotope exchange reactions: Use of initial rates to measure isotope effects on carbon acid ionization

Multistep hydrogen isotope exchange reactions, such as the íonization of a carbon acid via a carbanion intermediate in a protic solvent, when conducted using an isotopic tracer to monitor the exchange, have the unusual feature that their rate-determining steps always refer to the transfer of the tracer isotope and never to the isotope present in macroscopic amounts. This property of these reactions is discussed and rationalized using a free energy versus reaction coordinate diagram. It is further shown that this property does not invalidate a commonly used method of measuring kinetic isotope effects on carbon acid ionization in which rates of incorporation of tritium tracers into RH and RD substrates are compared, despite the fact that tritium transfer is rate determining in both exchanges, but it is valid only if initial rate measurements are used. When the comparison is made in a protio solvent, e.g., H₂O, the portion of the initial reaction which may be used depends strongly on the magnitude of the isotope effect. It ranges from less than 1% tritium incorporation for large isotope effects to 10% or more for isotope effects near unity. On the other hand, when a deuterated solvent, e.g., D₂O, is used, the range of validity of the method for large isotope effects is extended dramatically.     

Gas-phase fragmentation reactions of protonated glycerol and its oligomers: Metastable and collision-induced dissociation reactions,associated deuterium isotope effects and the structure of [C3H5O]+, [C2H5O]+, [C2H4O]+. and [C2H3O]+ ions

The chemistry of glycerol subjected to a high-energy particle beam was explored by studying the mass spectral fragmentation characteristics of gas-phase protonated glycerol and its oligomers by using tandem mass spectrometry. Both unimolecular metastable and collision-induced dissociation reactions were studied. Collision activation of protonated glycerol results in elimiation of H₂O and CH₃OH molecules. The resulting ions undergo further fragmentations. The origin of several fragment ions was established by obtaining their product and precursor ion spectra. Corresponding data for the deuterated analogs support those results. The structures of the fragment ions of compositions [C₃H₅O]⁺, [C₂H₅O]⁺, [C₂H₄O]^+. and [C₂H₃O]⁺ derived from protonated glycerol were also identified. Proton-bound glycerol oligomers fragment principally via loss of neutral glycerol molecules. Dissociation of mixed clusters of glycerol and deuterated glycerol displays normal secondary isotope effects.     

Simultaneous Determination of Methadone,Heroin, Cocaine and their Metabolites in Urine by GC‐MS

Abstract

A gas chromatographic‐mass spectrometric (GC‐MS) method for the determination of methadone, heroin, cocaine, and their metabolites in urine using Selected Ion Monitoring (SIM) was developed. Following a liquid‐liquid extraction with Toxitubes A^® and using their deuterated analogs as internal standards, the analytes were derivatized with 99:1 (v/v) N,O‐bis‐trimethylsilyl‐trifluoroacetamide/trimethylchlorosilane and injected by hand, in the splitless mode, at 240°C and a purging time of 0.75 min. The mass selective detector was kept at 300°C and molecules were ionized in the electron impact mode, using an energy of 70 eV. The detector response was linear for all drugs studied over the range 50–1000 ng/mL.     

Ion Exchange High Performance Liquid Chromatography of Leukotrienes

Abstract

A novel anion exchange liquid chromatographic system has been developed for isocratic separation of leukotrienes. Hydrophobic as well as ionic forces were found to influence the separation. By optimization of solvent strenght, ionic strenght and pH, amphoteric peptidoleukotrienes could be separated simultaneously with hydroxy fatty acids such as leukotriene B₄ and its ω-oxidized metabolites. To obtain a good buffering capacity of the mobile phase at optimum pH, a multicomponent buffer was developed.