Remote functional group directed C-H activation by an Ir(iii) phenanthroline complex.

The regioselectivity of the C-H activation of 1-butanol and 1-methoxybutane by an iridium(iii) phenanthroline complex was studied in the gas phase and revealed activation at gamma and delta carbons. In the ether, nearly exclusive gamma activation was observed. DFT calculations were used to explore the origin of this substrate-driven selectivity.

An Oxy-anion Accelerated [1,5]--Quinone Methide Shift During the Nucleophilic Epoxidation of Salicylfulvene.

A new facet of nucleophilic fulvene epoxidations has been uncovered. 6-Arylfulvenes containing an or hydroxyl group react with basic hydrogen peroxide in an unusual manner; the epoxidation of the fulvene exocyclic double bond is followed by a phenoxide ion initiated epoxide ring opening to form an -quinone methide (-QM) intermediate. The resulting cyclopentadienolate undergoes an unusual .

Singlet oxygenation of triquinacene, barrelene, and homobarrelene.

The singlet oxygenation of three polycyclic hydrocarbons, triquinacene, barrelene and homobarrelene was studied. Triquinacene reacted by way of a perepoxide intermediate, transferring an oxygen atom to another triquinacene molecule to give exclusively the mono epoxide. Barrelene, on the other hand, underwent a rare homo-Diels-Alder reaction with O to give the decomposition product from the initial tetracyclic 1,2-dioxolane leading to benzofuran.

Gas-Phase Dehydrogenation of Alkanes: C-H Activation by a Graphene-Supported Nickel Single-Atom Catalyst Model.

A gas-phase anionic nickel(0) fluorenyl complex is shown to effect the dehydrogenation of linear, branched, and cyclic alkanes via C-H activation. It performs dehydrogenations via a C-H insertion followed by β-hydride elimination. When given energy via collision-induced dissociation, the system is capable of second and third dehydrogenations to form dienes and aromatics such as benzene.

Substitution Reactions on Iodine and Bromine: Mechanisms for Facile Halogenations of Heterocycles.

Gas-phase techniques were used to examine the halogenation of deprotonated heterocycles by perfluoroaryl and perfluoroalkyl halides. The results indicate that S2@Br and S2@I reactions can be very facile and are effective means of halogenating heterocycles. 2-Iodoheptafluoropropane is exceptionally selective for S2@I reactions with yields upward of 90%.

Imidazolidin-4-ones via (3+2) cycloadditions of aza-oxyallyl cations onto ()-arylideneanilines.

In the course of our studies on the chemistry of oxyallyl species we uncovered a new (3+2) cycloaddition of aza-oxyallyl systems, generated in situ from -benzyloxy-2-chloroamides in the presence of NEt, onto -arylimines yielding imidazolidin-4-ones in moderate to good yields. The cycloadditions are regioselective. Computational modelling using DFT at the M062×/6-311+G** level is in support the observed regioselectivities.

Cyclopentadienones via a tandem -cyclopropylnitrone cyclization-cycloreversion sequence.

Aldonitrones derived from spiro[2.4]hepta-4,6-diene-1-carbaldehyde and its benzo analog undergo a tandem uncatalyzed intramolecular cyclopropane-nitrone cyclization-5,6-dihydro-1,2-oxazine cycloreversion to give cyclopentadienones. Similarly, the NH-nitrone generated in situ from spiro[cyclopropane-1,1'-indene]carbaldehyde oxime leads to benzocyclopentadienone (1-inden-1-one) by the same mechanism.

Diverse modes of reactivity of 6-(chloromethyl)-6-methylfulvene.

The title compound exhibits a number of reactivities toward nucleophiles/bases owing to the presence of several electrophilic and potentially nucleophilic sites in the molecule. We explored the reactions of 6-(chloromethyl)-6-methylfulvene with oxygen- and nitrogen nucleophiles and bases as well as a carbon-based nucleophile (an enamine) and realized all possible reactivity modes predicted on the basis of electrophilic and nucleophilic positions in this compound.

A Robust Analytical Approach for the Identification of Specific Protein Carbonylation Sites: Metal-Catalyzed Oxidations of Human Serum Albumin.

The formation of protein carbonyls in the metal-catalyzed oxidation of human serum albumin (HSA) is characterized using a new analytical approach that involves tagging the modification site with multiple hydrazide reagents. Protein carbonyl formation at lysine and arginine residues was catalyzed with copper and iron ions, and the resulting oxidation patterns in HSA are contrasted. A total of 18 modification sites were identified with iron ion catalysis and 14 with copper ion catalysis.

Effect of Ring Size and Migratory Groups on [1,n] Suprafacial Shift Reactions. Confirmation of Aromatic and Antiaromatic Transition-State Character by Ring-Current Analysis.

Suprafacial sigmatropic shift reactions of 5-substituted cyclopentadienes, 3-substituted cyclopropenes, and 7-substituted cycloheptatrienes have been studied computationally at the MP2/6-31+G* level for structures and energetics and with the ipsocentric method at the CHF/6-31G** level to calculate current-density maps. The hydrogen shifts in cyclopentadienes have a diatropic ring current indicating aromatic, cyclopentadienide anion character. This result stands in contrast to the fluorine shift in 5-fluorocyclopentadiene which requires much more energy and has a paratropic ring current in the TS pointing to antiaromatic, cyclopentadienyl cation character.

Unusual hydroxyl effect on fulvene endoperoxide decompositions.

The thermal decomposition of fulvene endoperoxides ordinarily proceeds via an allene oxide intermediate affording oxepin-2()-one derivatives. We have now uncovered new, unusual pathways in these decompositions where the presence of a hydroxyl group on the alkyl or aryl attached to the fulvene exocyclic double bond has a profound effect on the fate of the reactive intermediates derived from the unstable endoperoxides. Computational work supports the proposed mechanistic pathways.

A cleavable biotin tagging reagent that enables the enrichment and identification of carbonylation sites in proteins.

The utility of a new, cleavable tag for identifying and enriching protein carbonyls is examined. Using a model system, human serum albumin modified with acrolein, the EZ-Link alkoxyamine-PEG4-SS-PEG4-biotin affinity tag, was tested for its ability to label protein carbonyls in proteomic analyses of protein carbonylation. The efficiency of the labeling was assayed and compared to standard biotin hydrazide reagents.

A mass spectrometric method for rapidly assaying the chiral selectivities of the copper(I) complexes of C2-symmetric ligands.

A gas-phase method for rapidly assaying the enantioselectivity of metal-centered catalysts is presented. It relies on gas-phase equilibrium measurements in a quadrupole ion trap mass spectrometer. A group of well-established C2-symmetric bis-oxazoline copper(I) complexes was used to identify chiral probe reagents that are capable of profiling the quality of the asymmetric environment provided by the metal complex.

The Competition between Elimination Pathways in the Reactions of a Wide Variety of Bases with 2-Fluoro- and 2-Chlorobutane in the Gas Phase.

Ab initio methods are used to examine the regio- and stereoselectivities of the elimination reactions of 2-fluorobutane and 2-chlorobutane with a series of nucleophiles (F(-), HO(-), CH3O(-), (CH3)3CO(-), NH2(-), CH3(-), H(-), Cl(-), HS(-), and PH2(-)). The data suggest that regiochemistry is most closely related to the nature of the transition state on the E2 spectrum with E1cb-like reactions favoring the least-substituted alkene product and E1-like reactions favoring the most-substituted alkene product. There appears to be no correlation between the extent of π-bond formation (as measured by the Cα-Cβ distance) and the preference for forming the more highly substituted alkene.

Development and Evaluation of a Variable-Temperature Quadrupole Ion Trap Mass Spectrometer.

A new, variable-temperature mass spectrometer system is described. By applying polyimide heating tape to the end-cap electrodes of a Bruker (Bremen, Germany) Esquire ion trap, it is possible to vary the effective temperature of the system between 40 and 100°C. The modification does not impact the operation of the ion trap and the heater can be used for extended periods without degradation of the system.

Are copper(I) carbenes capable intermediates for cyclopropanations? The case for ylide intermediates.

A novel approach is used to synthesize a stable, ligated copper(I) carbene in the gas phase that is capable of typical metal carbenoid chemistry. However, it is shown that copper(I) carbenes generally undergo rapid unimolecular rearrangements including insertions into copper-ligand bonds and Wolff rearrangements. The results indicate that most copper(I) carbenes are inherently unstable and would not be viable intermediates in condensed-phase applications; an alternative intermediate that is less prone to rearrangements is required.

Pyrrolidine catalyzed reactions of cyclopentadiene with α,β-unsaturated carbonyl compounds: 1,2- versus 1,4-additions.

A systematic study of the reactions of cyclopentadiene with α,β-unsaturated carbonyl compounds in the presence of catalytic pyrrolidine-HO revealed that the reactions can either proceed with a Michael attack at the β-carbon of enone, or 1,2-addition to the carbonyl, leadingeither to 4-cyclopentadienyl-2-butanones or 6-vinylfulvenes. The former can be isolated and/or converted to the corresponding 1,2-dihydropentalenes with base (or in one-pot at longer reaction times). Substitution pattern on the enones on the competing pathways have been studied and consistent mechanisms are proposed.

Intermolecular C-H Bond Activation by a Cationic Iridium(III) Dichloride Phenanthroline Complex.

It is demonstrated that a cationic iridium(III) dichloride phenanthroline complex is capable of C-H activation and H/D exchange. It can cleave benzylic and unactivated secondary C-H bonds, but exhibits unique selectivity when compared to similar systems that have been studied in the condensed phase. Gas-phase rate constants and kinetic isotope effects are reported for a variety of substrates and the analysis is supported by DFT calculations at the M06/QZVP level.

Protonated polycyclic aromatic nitrogen heterocyclics: proton affinities, polarizabilities, and atomic and ring charges of 1-5-ring ions.

Calculated proton affinities, polarizabilities, and some ionization energies and atomic and ring NBO charges are reported for 31 polycyclic aromatic nitrogen heterocyclics (PANHs) with 1-5 rings, calculated on the on the M06-2X/6-311+g**//B3LYP/6-31g* level of theory. The calculated proton affinities from 226 to 241 kcal mol(-1) for 3-5-ring compounds, predict well the relative experimental values. The proton affinities increase with increasing molecular size and show a linear correlation with polarizabilities.

Protonation energies of 1-5-ring polycyclic aromatic nitrogen heterocyclics: comparing experiment and theory.

Polycyclic nitrogen heterocyclic compounds (PANHs) can be protonated in the gas phase in mass spectrometry, in solution in acidic and biological environments, and if present, in interstellar clouds. Intrinsic molecular effects on PANH basicities can be observed by their gas phase protonation thermochemistry. We determined the gas phase basicities/proton affinities (GBs/PAs) of prototype one-nitrogen, 3-5-ring PANH compounds of increasing sizes and polarizabilities by kinetic bracketing, using proton transfer reactions to reference bases.

Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.

The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group).

Electron flow into cytochrome c coupled with reactive oxygen species from the electron transport chain converts cytochrome c to a cardiolipin peroxidase: role during ischemia-reperfusion.

Background: Cytochrome c (Cyt c) is a mobile component of the electron transport chain (ETC.) which contains a tightly coordinated heme iron. In pathologic settings, a key ligand of the cyt c's heme iron, methionine (Met80), is oxidized allowing cyt c to participate in reactions as a peroxidase with cardiolipin as a target.

Paraquat exposure and Sod2 knockdown have dissimilar impacts on the Drosophila melanogaster carbonylated protein proteome.

Exposure to Paraquat and RNA interference knockdown of mitochondrial superoxide dismutase (Sod2) are known to result in significant lifespan reduction, locomotor dysfunction, and mitochondrial degeneration in Drosophila melanogaster. Both perturbations increase the flux of the progenitor ROS, superoxide, but the molecular underpinnings of the resulting phenotypes are poorly understood. Improved understanding of such processes could lead to advances in the treatment of numerous age-related disorders.

Reactivity in the nucleophilic aromatic substitution reactions of pyridinium ions.

The "element effect" in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, L = F > NO2 > Cl ≈ Br > I, in activated aryl substrates. A different leaving group order is observed in the substitution reactions of ring-substituted N-methylpyridinium compounds with piperidine in methanol: 2-CN ≥ 4-CN > 2-F ∼ 2-Cl ∼ 2-Br ∼ 2-I. The reactions are second-order in [piperidine], the mechanism involving rate determining hydrogen-bond formation between piperidine and the substrate-piperidine addition intermediate followed by deprotonation of this intermediate.

Effect of allylic groups on S(N)2 reactivity.

The activating effects of the benzyl and allyl groups on S(N)2 reactivity are well-known. 6-Chloromethyl-6-methylfulvene, also a primary, allylic halide, reacts 30 times faster with KI/acetone than does benzyl chloride at room temperature. The latter result, as well as new experimental observations, suggests that the fulvenyl group is a particularly activating allylic group in S(N)2 reactions.