Vapor phase phototransposition of pyrazine deuterium labeling studies

2,5-Dideuteriopyrazine (1-2,5-d₂) and 2,6-dideuteriopyrazine (1-2,6-d₂) phototranspose in the vapor phase to mixtures of 4,6-dideuteriopyrimidine (2-4,6-d₂) and 2,5-dideuteriopyrimidine (2-2,5-d₂) or 4,5-dideuteropyrimidine (2-4,5-d₂) and 2,4-dideuteriopyrimidine (2-2,4-d₂), respectively. In each case, a trace quantity of a dideuteriopyridazine (7-d₂) photoproduct was also observed. These products are consistent with a diazaprefulvene mechanism involving, 2,6-bonding, one or two nitrogen migrations, and rearomatization.     

Vapor-phase photochemistry of methyl- and cyanopyridines: deuterium labeling studies

The three isomeric methylpyridines and the three isomeric cyanopyridines each constitute a photochemical triad. Irradition of each methylpyridine or each cyanopyridine in the vapor phase at 254 nm results in the formation of the other two isomers as primary photoproducts. Dideuteration of the 2-substituted or 3-substituted methyl or cyanopyridines expanded each triad to a pentad. Due to symmetry, 2,6-dideuteration of 4-methyl-or 4-cyanopyridine did not expand the triad. Trideuteration of 4-methylpyridine removed this symmetry and resulted in a photochemical pentad. These results are consistent with a mechanism involving 2,6-photocylization, migration of nitrogen around the five sides of the cyclopentenyl ring, and rearomatization. This mechanism exactly predicts the observed distribution of deuterium in the photoproducts.     

Applications and limitations of deuterium labeling methods to neutron scattering studies of polymers

Deuterium labeling techniques have been widely used to study polymer chain configuration and motion, based on the assumption that the H- and D- chains are thermodynamically identical and that the interaction parameter between them, X_HD is zero. By an appropriate choice of the degree of polymerization and temperature, both critical scattering and phase separation can be made to occur, due solely to the small but finite thermodynamic differences between protonated and deuterated molecules. These experiments helped delineate the range of validity of the assumptions which had been used hitherto in neutron scattering studies of polymers. The majority of previous experiments, carried out at modest molecular weights, have been shown to be in large part unaffected by such effects.     

Mechanism of the hydrosilylation reaction of alkenes at porous silicon: experimental and computational deuterium labeling studies

The mechanism of the formation of Si-C bonded monolayers on silicon by reaction of 1-alkenes with hydrogen-terminated porous silicon surfaces has been studied by both experimental and computational means. We propose that monolayer formation occurs via the same radical chain process as at single-crystal surfaces: a silyl radical attacks the 1-alkene to form both the Si-C bond and a radical center on the beta-carbon atom. This carbon radical may then abstract a hydrogen atom from a neighboring Si-H bond to propagate the chain. Highly deuterated porous silicon and FTIR spectroscopy were used to provide evidence for this mechanism by identifying the IR bands associated with the C-D bond formed in the proposed propagation step. Deuterated porous silicon surfaces formed by galvanostatic etching in 48% DF/D2O:EtOD (1:1) electrolytes showed a 30% greater density of Si-D sites on the surface than Si-H sites on hydrogen-terminated porous silicon surfaces prepared in the equivalent H-electrolyte. The thermal reaction of undec-1-ene and the Lewis acid catalyzed reaction of styrene on a deuterated surface both resulted in alkylated surfaces with the same C-C and C-H vibrational features as formed in the corresponding reactions at a hydrogen-terminated surface. However, a broad band around 2100 cm(-1) was observed upon alkylating the deuterated surfaces. Ab initio and density functional theory calculations on small molecule models showed that the integrated absorbance of this band was comparable to the intensity expected for the C-D stretches predicted by the chain mechanism. The calculations also indicate that there is substantial interaction between the hydrogen atoms on the beta-carbons and the hydrogen atoms on the Si(111)-H surface. These broad 2100 cm(-1) features are therefore assigned to C-D bands arising from the involvement of surface D atoms in the hydrosilylation reactions, while the line broadening can be explained partly by interaction with neighboring surface atoms/groups.     

Mechanistic studies of olefin and alkyne trimerization with chromium catalysts: deuterium labeling and studies of regiochemistry using a model chromacyclopentane complex

A system for catalytic trimerization of ethylene utilizing chromium(III) precursors supported by diphosphine ligand PNP(O4) = (o-MeO-C6H4)2PN(Me)P(o-MeO-C6H4)2 has been investigated. The mechanism of the olefin trimerization reaction was examined using deuterium labeling and studies of reactions with alpha-olefins and internal olefins. A well-defined chromium precursor utilized in this studies is Cr(PNP(O4))(o,o'-biphenyldiyl)Br. A cationic species, obtained by halide abstraction with NaB[C6H3(CF3)2]4, is required for catalytic turnover to generate 1-hexene from ethylene. The initiation byproduct is vinylbiphenyl; this is formed even without activation by halide abstraction. Trimerization of 2-butyne is accomplished by the same cationic system but not by the neutral species. Catalytic trimerization, with various (PNP(O4))Cr precursors, of a 1:1 mixture of C2D4 and C2H4 gives isotopologs of 1-hexene without H/D scrambling (C6D12, C6D8H4, C6D4H8, and C6H12 in a 1:3:3:1 ratio). The lack of crossover supports a mechanism involving metallacyclic intermediates. Using a SHOP catalyst to perform the oligomerization of a 1:1 mixture of C2D4 and C2H4 leads to the generation of a broader distribution of 1-hexene isotopologs, consistent with a Cossee-type mechanism for 1-hexene formation. The ethylene trimerization reaction was further studied by the reaction of trans-, cis-, and gem-ethylene-d2 upon activation of Cr(PNP(O4))(o,o'-biphenyldiyl)Br with NaB[C6H3(CF3)2]4. The trimerization of cis- and trans-ethylene-d2 generates 1-hexene isotopomers having terminal CDH groups, with an isotope effect of 3.1(1) and 4.1(1), respectively. These results are consistent with reductive elimination of 1-hexene from a putative Cr(H)[(CH2)4CH=CH2] occurring much faster than a hydride 2,1-insertion or with concerted 1-hexene formation from a chromacycloheptane via a 3,7-H shift. The trimerization of gem-ethylene-d2 has an isotope effect of 1.3(1), consistent with irreversible formation of a chromacycloheptane intermediate on route to 1-hexene formation. Reactions of olefins with a model of a chromacyclopentane were investigated starting from Cr(PNP(O4))(o,o'-biphenyldiyl)Br. alpha-Olefins react with cationic biphenyldiyl chromium species to generate products from 1,2-insertion. A study of the reaction of 2-butenes indicated that beta-H elimination occurs preferentially from the ring CH rather than exo-CH bond in the metallacycloheptane intermediates. A study of cotrimerization of ethylene with propylene correlates with these findings of regioselectivity. Competition experiments with mixtures of two olefins indicate that the relative insertion rates generally decrease with increasing size of the olefins.     

Identification of fragmentation channels of dinucleotides using deuterium labeling

The fragmentation of the totally deuterated dinucleotide dAT⁻ in labile positions (heteroatom-bound hydrogens) was compared for different MS/MS methods: CID, IRMPD, and EID. These experiments allowed us to affirm the coexistence of several fragmentation channels. They can be classified according to the involvement of nonlabile or labile protons in the fragmentation process. Moreover, double resonance experiments were performed in IRMPD and EID. They demonstrated the existence of consecutive fragmentation processes. The probability with which each channel is taken depends on the fragmentation technique used, i. e., the energy and the time scale of the method. The fragmentation channels that involve labile protons requiring peculiar three-dimensional structures are entropically unfavorable and enthalpically favorable. They are more observed in IRMPD and EID. The involvement of labile and, therefore, exchangeable protons in the fragmentation mechanism casts doubt on the use of tandem mass spectrometry to localize incorporated deuteriums in oligonucleotides.     

The effect of deuterium labeling on the width of a ‘metastable peak’

Studies have been made of the energy release during the decomposition of metastable ions in the mass spectra of pyrazine, pyrazine-d₄, pyrimidine, pyrimidine-d₄, pyridazine and symmtriazine. In all the compounds except pyridazine very small amounts of energy have been measured in some processes. The recorded energy release of 187 μeV for a transition of the symmtriazine molecular ion is the smallest energy release yet recorded. In the case of pyrazine and pyrimidine the energy release in one transition was found to be smaller than in the corresponding transition in the -d₄ analogues.     

Use of deuterium labeling studies to determine the stereochemical outcome of palladium migrations during an asymmetric intermolecular Heck reaction

A series of deuterium labeling experiments showed that Pd migrations during an intermolecular asymmetric Heck reaction between phenyl triflate and various deuterated 2,3-dihydrofurans (2b, 2c, 2d, 2e) occurs exclusively by either syn-1,2-dyotropic shifts or a syn-chain-walking mechanism; no evidence was observed to support anti-1,2-dyotropic shifts or anti-beta-H Pd eliminations during the formation of 6 and 7.     

Molecular hydrogen tweezers: structure and mechanisms by neutron diffraction, NMR, and deuterium labeling studies in solid and solution

The mechanism of reversible hydrogen activation by ansa-aminoboranes, 1-N-TMPH-CH(2)-2-[HB(C(6)F(5))(2)]C(6)H(4) (NHHB), was studied by neutron diffraction and thermogravimetric mass-spectroscopic experiments in the solid state as well as with NMR and FT-IR spectroscopy in solution. The structure of the ansa-ammonium borate NHHB was determined by neutron scattering, revealing a short N-H···H-B dihydrogen bond of 1.67 ?. Moreover, this intramolecular H-H distance was determined in solution to be also 1.6-1.8 ? by (1)H NMR spectroscopic T(1) relaxation and 1D NOE measurements. The X-ray B-H and N-H distances deviated from the neutron and the calculated values. The dynamic nature of the molecular tweezers in solution was additionally studied by multinuclear and variable-temperature NMR spectroscopy. We synthesized stable, individual isotopic isomers NDDB, NHDB, and NDHB. NMR measurements revealed a primary isotope effect in the chemical shift difference (p)Δ(1)H(D) = δ(NH) - δ(ND) (0.56 ppm), and hence supported dihydrogen bonding. The NMR studies gave strong evidence that the structure of NHHB in solution is similar to that in the solid state. This is corroborated by IR studies providing clear evidence for the dynamic nature of the intramolecular dihydrogen bonding at room temperature. Interestingly, no kinetic isotope effect was detected for the activation of deuterium hydride by the ansa-aminoborane NB. Theoretical calculations attribute this to an "early transition state". Moreover, 2D NOESY NMR measurements support fast intermolecular proton exchange in aprotic CD(2)Cl(2) and C(6)D(6).     

On the stereospecific reduction of vinylsulfoxides with thepossibility of deuterium labeling

Upon treating triene sulfoxide 2 or 3 in the of methanol (internal proton source) in ether with -butyllithium, the reduced product 4b or 4c, respectively, is obtained with retention of configuration. A deuterium label can be incorporated by using methanol-0-d₁ as the internal proton source.     

Some mass spectral and analytical aspects of deuterium labeling of straight-chain olefins

A calculation method has been developed to enhance the effect of deuterium labeling in the mass spectra of linear vicinal dideuterioalkanes (LVDA). Individual LVDA can be identified from these enhanced spectra. Single carbon-number mixtures of LVD nonanes and LVD decanes have been analyzed successfully using matrices derived from spectra of standards. In addition, enhanced mass spectra have been predicted for all of the LVD heptadecanes and LVD nonadecanes. Matrices have been constructed from the predicted spectra, and preliminary tests of these matrices have been conducted. All identifications and analytical results on the LVDA studied can be used to identify the precursor olefins.     

Flame emission studies of several metal chlorides with vapor-phase sampling

A method is described for the production of spectra of aluminum chloride, iron(III) chloride, silicon tetrachloride and titanium tetrachloride vapors by flame emission spectrometry. The aluminum and iron(III) chloride vapors were prepared by heating solid samples in reaction flasks; silicon and titanium tetrachlorides have sufficient vapor pressures at ambient temperatures to produce vapor-phase samples. Techniques have been developed to introduce the sample into the flame as a vapor, and to accommodate a large concentration of sample while requiring minimum preparation. Spectra were obtained individually and as a mixture over 240–600 nm. The analytical wavelength was chosen for each element, and 10-s integrations were made by utilizing a microcomputer to slew rapidly to the line of interest, hold for 10 s on the emission line, move off wavelength, hold for a 10-s background measurement and slew rapidly to the next line of interest. The microcomputer was also used to digitize and display the number of photons counted.     

Purification of pyridine for voltammetric studies : Effect of impurities

Purification of pyridine by zone fractional crystallization reduces the concentration of prewave-producing contaminant below polarographic detection limits, i.e., 0.01 mM. A qualitative test based on the stability of the free radical diphenylpicrylhydrazyl has shown the method to be capable of reducing the concentration of proton-releasing impurities. Water is also removed. Investigation of the effect of the contaminants in normal reagent-grade pyridine on the electrocapillary curves and polarograms of pyridine solutions containing lithium perchlorate and tetraethylammonium perchlorate as background electrolytes in the presence and absence of oxygen, has indicated that the impurities are capable of changing the mechanism for the electrochemical reduction of oxygen in pyridine.     

Heterogeneous atmospheric aerosol chemistry: laboratory studies of chemistry on water droplets

Heterogeneous chemical reactions on aerosol particles play a pivotal role in atmospheric chemistry. In this review, the fundamental concepts underlying the chemical dynamics of liquid aerosol droplets are discussed, with particular emphasis on the properties of the aqueous-air interface and the reaction mechanisms of key chemical processes. Recent laboratory studies of heterogeneous chemistry on aqueous aerosol particles are reviewed, with techniques that probe the gas phase, liquid phase and the interface directly, discussed in turn.     

Stereochemistry of the macrocyclization and elimination steps in taxadiene biosynthesis through deuterium labeling

Taxadiene synthase catalyzes the cyclization of (E,E,E)-geranylgeranyl diphosphate (GGPP) to taxa-4(5),11(12)-diene (Scheme 1, 5 --> 2) as the first committed step of Taxol biosynthesis. Deuterated GGPPs labeled stereospecifically at C-1, C-4, and C-16 were synthesized and incubated with recombinant taxadiene synthase from Taxus brevifolia to elucidate the stereochemistry of the cyclization reaction at these positions. The deuterium-labeled taxadienes obtained from (R)-[1-(2H1)]-, (S)-[1-(2H1)]-, and [16,16,16-(2H3)]GGPPs (9, 10, and 23b) were established to have deuterium in the 2alpha and 2beta CH2 and 16CH3 positions, respectively, by high-field 1H NMR spectroscopy (eqs 1-3). Incubation of (R)-[4-(2H1)]GGPP (17) with the recombinant enzyme gave a 10:10:80 mixture of [5beta-(2H1)]taxa-3(4),11(12)-diene, [5beta-(2H1)]taxa-4(20),11(12)-diene, and unlabeled taxa-4(5),11(12)-diene according to GC/MS analyses of the products (eq 4). It follows that C-1 of GGPP underwent inversion of configuration, that the A ring cyclization occurs on the si face of C15, and that the terminating proton abstraction removes H5beta from the final taxenyl carbocation intermediate. Thus, the C1-C14 and C15-C10 bonds are formed on the opposite faces of the 14,15 double bond of the substrate, i.e., overall anti electrophilic addition. The implications of these findings for the mechanism of the cyclization and rearrangement are discussed.     

The analytical chemistry of the pyridine thiocyanates—II The separation of ruthenium and palladium

A procedure is described for the separation and subsequent colorimetric determination of ruthenium and palladium as complex and ammine-type thiocyanates respectively, using solvent extraction. Suggestions are put forward as to the nature of the ruthenium complex occurring in solution.     

Bioorthogonal organic chemistry in living cells: novel strategies for labeling biomolecules

The chemical labeling of biomolecules continues to be an important tool for the study of their function and cellular fate. Attention is increasingly focused on labeling of biomolecules in living cells, since cell lysis introduces many artefacts. In addition, with the advances in biocompatible synthetic organic chemistry, a whole new field of opportunity has opened up, affording high diversity in the nature of the label as well as a choice of ligation reactions. In recent years, several different two-step labeling strategies have emerged. These rely on the introduction of a bioorthogonal attachment site into a biomolecule, then ligation of a reporter molecule to this site using bioorthogonal organic chemistry. This Perspective focuses on these techniques, their implications and future directions.     

Hydrogen and deuterium atoms in octasilsesquioxanes: experimental and computational studies

The rate of detrapping of atomic hydrogen from several octasilsesquioxanes is the same for dissolved and solid samples and is independent of the presence of other species such as free radicals or oxygen; varying the cage substituents leads to only minor differences in the activation parameters. Hydrogen atoms are found to be more strongly stabilized in homosubstituted octasilsesquioxanes compared with singly Ge-substituted cages. A kinetic isotope effect observed for the detrapping of H and D from MeT(8) is ascribed to the difference in the zero-point energies of the trapped atoms. There is a secondary H/D isotope effect in the temperature dependence of the (29)Si-superhyperfine splitting constants in the range 228-353 K. Cage relaxation has a substantial effect on the detrapping barrier but little influence on the intracage potential. Calculations using a rigid cage approximation give satisfactory agreement with zero-point parameters extracted from experimental data. Different model chemistries yield qualitatively different pictures of the dependence of the hyperfine coupling constant of the trapped H atom upon the detrapping coordinate. Within an isotropic approximation of the vibrational displacements, the B3LYP data give fairly close agreement with the experimental temperature dependence, subject to a shift of the absolute value related to known weaknesses of the method. For the Si(7)Ge cage, it is found that the transition state in which the H atom passes through a Ge-containing face is strongly favored, accounting for the larger detrapping rate parameters observed experimentally for this species.     

The use of protium and deuterium analogues in mechanistic studies of thiazole syntheses

The mechanisms of two reactions which give isomeric thiazol-5-yl ketones have been elucidated by work with substrates containing pairs of acyl groups and their deuterium-substituted analogues.