A short,highly efficient synthesis of coenzyme Q(10)

The most efficient synthesis reported to date of ubiquinone (CoQ10) is described. A sequence consisting of six operations is involved which leads to crystalline material in an overall yield of >64%.     

Synthesis of a novel constrained α-amino acid with quinoxaline side chain: 7-amino-6,7-dihydro-8H-cyclopenta[g]quinoxaline-7-carboxylic acid

A novel constrained 7-amino-6,7-dihydro-8H-cyclopenta[g]quinoxaline-7-carboxylic acid derivative was prepared starting from 4,5-dimethyl-o-phenylenediamine.     

Formation and characterization of protein-protein complexes in vacuo

Gas-phase reactions between multiply charged positive and negative protein ions are carried out in a quadrupole ion trap mass spectrometer. The ions react with one another by proton transfer and complex formation. Proton transfer products and complexes are formed via competitive processes in single ion/ion encounters. The relative contributions of proton transfer versus complex formation are dependent upon the charges of the ions as well as other characteristics of the ions yet to be clearly delineated. No fragmentation of covalent bonds of the protein reactants is observed. A model that considers the trajectories associated with ion/ion interactions appears to hold the most promise in accounting for the results. The formation of bound ion/ion orbits appears to play an important role in determining overall reaction kinetics as well as the distribution of ion/ion reaction products. Tandem mass spectrometry is used to compare protein complexes formed in the gas-phase with those formed initially in solution and subsequently liberated by electrospray; it is shown that both forms of complex dissociate similarly, but the complexes formed in the gas phase can retain a "memory" of their method of formation.     

SO<Stack><Subscript>2</Subscript><Superscript>−·</Superscript></Stack> electron transfer ion/ion reactions with disulfide linked polypeptide ions

Multiply-charged peptide cations comprised of two polypeptide chains (designated A and B) bound via a disulfide linkage have been reacted with SO2-* in an electrodynamic ion trap mass spectrometer. These reactions proceed through both proton transfer (without dissociation) and electron transfer (with and without dissociation). Electron transfer reactions are shown to give rise to cleavage along the peptide backbone, loss of neutral molecules, and cleavage of the cystine bond. Disulfide bond cleavage is the preferred dissociation channel and both Chain A (or B)-S* and Chain A (or B)-SH fragment ions are observed, similar to those observed with electron capture dissociation (ECD) of disulfide-bound peptides. Electron transfer without dissociation produces [M + 2H]+* ions, which appear to be less kinetically stable than the proton transfer [M + H]+ product. When subjected to collision-induced dissociation (CID), the [M + 2H]+* ions fragment to give products that were also observed as dissociation products during the electron transfer reaction. However, not all dissociation channels noted in the electron transfer reaction were observed in the CID of the [M + 2H]+* ions. The charge state of the peptide has a significant effect on both the extent of electron transfer dissociation observed and the variety of dissociation products, with higher charge states giving more of each.     

Loss of charged versus neutral heme from gaseous holomyoglobin ions.

The dissociation of holomyoglobin ions ranging in charge state from +10 to +2 has been studied using collisional activation in a quadrupole ion trap. Collisional activation times and amplitudes were varied to investigate the effects of these variables on dissociation of the heme group from the holoprotein. The onset of neutral heme loss occurs at a lower activation amplitude than loss of charged heme. For solutions of ferri-myoglobin, charged heme loss was prominent for +10 to +4 holomyoglobin ions, while neutral heme loss product was found to be dominant for charge states +3 and +2. For any given charge state, activation of holomyoglobin ions from a solution containing primarily ferro-myoglobin yielded significantly more abundant neutral heme loss products than was observed for activation of ions from solutions containing primarily ferri-myoglobin. The relative concentrations of the two oxidation states were shown to be affected by redox chemistry within the nano-electrospray emitter used in this work. Results from a double activation experiment revealed that the precursor ions of a given charge state contained a mixture of two populations, with ferro-myoglobin giving rise to neutral heme loss upon dissociation and ferri-myoglobin yielding charged heme. No evidence for electron transfer upon collisional activation of ferri-myoglobin ions was observed. Furthermore, little or no evidence for electron transfer associated with ion/ion reactions with anions derived from perfluoro-1,3-dimethylcyclohexane was observed. Definitive results could not be drawn for the lowest precursor ion charge states (+3 and +2) due to low dissociation efficiencies.     

Tweaking copper hydride (CuH) for synthetic gain. A practical,one-pot conversion of dialkyl ketones to reduced trialkylsilyl ether derivatives

[reaction: see text] Variations in the reagents and stoichiometries used to generate CuH in situ, as well as the nature of the ligands present, have led to a very efficient and inexpensive method for effecting hydrosilylations of dialkyl ketones.     

Synthesis and mutagenic potency of structural isomers of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Synthesis of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), three structural isomers, and two desphenyl PhIP congeners has been carried out. Mutagenic potency was evaluated using S. typhimurium strain TA98 in the Ames test. Mutagenic potency increased in relation to structural features in these heterocyclic amines that allow extended resonance between the phenyl and imidazo[4,5‐b]pyridine N²‐amino substituents. By contrast, PhIP isomers, whose substitution disallows involvement of the phenyl group in their aminoimidazo resonance hybrids, and desphenyl congeners were from 86‐ to 234‐fold less mutagenic than PhIP.     

Introducing efficient palladium catalyzed cross coupling reaction of tertiary alcohols and aroyl chlorides for the synthesis of highly substituted esters

Esters are chemical compounds with many practical uses. The common type of esterification is called the Fischer esterification. Another one is by the action of acid chlorides on alcohols but not with tertiary alcohols. The stable carbenium ions formed from tertiary alcohols favor elimination and the byproduct, hydrogen chloride prevents ester formation. In this new report, palladium inserted ArCOPdCl species reacts with tertiary alcohols and cross-coupling under microwave heating, minimizes the formation of probable carbenium ion, and promotes successful production of highly substituted esters in good to high yields.     

Electron transfer versus proton transfer in gas-phase ion/ion reactions of polyprotonated peptides

The ion/ion reactions of several dozen reagent anions with triply protonated cations of the model peptide KGAILKGAILR have been examined to evaluate predictions of a Landau-Zener-based model for the likelihood for electron transfer. Evidence for electron transfer was provided by the appearance of fragment ions unique to electron transfer or electron capture dissociation. Proton transfer and electron transfer are competitive processes for any combination of anionic and cationic reactants. For reagent anions in reactions with protonated peptides, proton transfer is usually significantly more exothermic than electron transfer. If charge transfer occurs at relatively long distances, electron transfer should, therefore, be favored on kinetic grounds because the reactant and product channels cross at greater distances, provided conditions are favorable for electron transfer at the crossing point. The results are consistent with a model based on Landau-Zener theory that indicates both thermodynamic and geometric criteria apply for electron transfer involving polyatomic anions. Both the model and the data suggest that electron affinities associated with the anionic reagents greater than about 60-70 kcal/mol minimize the likelihood that electron transfer will be observed. Provided the electron affinity is not too high, the Franck-Condon factors associated with the anion and its corresponding neutral must not be too low. When one or the other of these criteria is not met, proton transfer tends to occur essentially exclusively. Experiments involving ion/ion attachment products also suggest that a significant barrier exists to the isomerization between chemical complexes that, if formed, lead to either proton transfer or electron transfer.