Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents

We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these reagents offer multiple analytical figures of merit including, (1) robust targeting of peptide N-termini and lysyl side chains, (2) optimal mass spectrometry ionization efficiency through regeneration of primary amines on labeled peptides, (3) an amino acid-based mass tag that incorporates heavy isotopes of carbon, nitrogen, and oxygen to ensure matched physicochemical and MS/MS fragmentation behavior among labeled peptides, and (4) a molecularly efficient architecture, in which the majority of hetero-atom centers can be used to synthesize a variety of nominal mass and sub-Da isotopologue stable isotope reagents. We demonstrate the performance of these reagents in well-established strategies whereby up to four channels of peptide isotopomers, each separated by 4 Da, are quantified in MS-level scans with accuracies comparable to current commercial reagents. In addition, we utilize the PAL scaffold to create isotopologue reagents in which labeled peptide analogs differ in mass based on the binding energy in carbon and nitrogen nuclei, thereby allowing quantification based on MS or MS/MS spectra. We demonstrate accurate quantification for reagents that support 6-plex labeling and propose extension of this scheme to 9-channels based on a similar PAL scaffold. Finally, we provide exemplar data that extend the application of isotopologe-based quantification reagents to medium resolution, quadrupole time-of-flight mass spectrometers.

Preparation and characterization of electrostrictive polyurethane films with conductive polymer electrodes

All-polymer electrostrictive soft films were developed for the first time by depositing conductive polymer (polypyrrole) directly on both sides of solution-cast electrostrictive polyurethane elastomer films. The final composite films are flexible with strong adhesion between the polyurethane film and the conductive polymer electrode. The conductivity (sheet resistivity ∼1000 Ω/□), of the polymer electrode is appropriate for its intended use. The compatible interface between the polypyrrole electrode polymer and the electrostrictive polyurethane significantly improves the acoustic and optical transparency of these composite films, compared with using a metal electrode film. The all-polymer films also exhibit comparable dielectric properties to gold-electroded polyurethane films in the temperature range from −40^°C to +80^°C. The temperature range covers the soft segment glass transition temperature of the polyurethane elastomers, which is about −20^°C. The films also show large electric field induced strain responses which are dependent on film thickness and measurement frequency. The electrostrictive characteristics in the all-polymer films show similarities to those of the films with gold electrodes under identical measurement conditions. © 1998 John Wiley & Sons, Ltd.     

Self-assembled networks of conducting polyaniline in bulk polymers: A new class of conducting polymer blends

This review of the current status of conducting polymers will focus on recent progress which demonstrates that the initial promise of the late 1970's has become reality. Conducting polymers are now available as materials with truly unique properties: They combine the important electronic and optical properties of semiconductors and metals with the attractive mechanical properties and processing advantages of polymers. Conducting polymer blends based upon polyaniline (PANI) are a new class of materials in which the threshold for the onset of electrical conductivity (σ) can be reduced to volume fractions below 1%, well below that required for classical percolation (16% by volume for globular conducting objects dispersed in an insulating matrix in three dimensions). The origin of this remarkably low threshold for the onset of electrical conductivity is the self-assembled network morphology of the PANI polyblends which forms during the course of liquid-liquid separation. Since the average density of the conducting network near threshold is small, the conductivity increases smoothly and continuously over many orders of magnitude as the concentration of conducting polymer increases above threshold. The low percolation threshold and the continuous increase of σ(f) above threshold are particularly important; as a result of this combination, conducting polyblends can be reproducibly fabricated with controlled levels of electrical conductivity while retaining the desired mechanical properties of the matrix polymer.^1-3)     

Applications of benzotriazole methodology in heterocycle ring synthesis and substituent introduction and modification

Applications of benzotriazole methodology for the preparation of heterocyclic compounds are reviewed. The characteristic advantages of benzotriazole as a synthetic auxiliary are first briefly considered. This is followed by a summary of its use in ring synthesis in which the construction of small; five-membered; six-membered; and larger heterocyclic rings using benzotriazole methodology are each examined separately. Finally, consideration of the use of benzotriazole in the ring annulation - particularly benzannulation - of heterocycles. Subsequent sections deal with the introduction of substituents into aromatic heterocycles; the ring substitution of saturated heterocycles; and benzotriazole assisted modification of heterocyclic substituents. The present review supplements a recent comprehensive review of benzotriazole chemistry [1] which covers the literature through 1996.     

200 years of practical electroanalytical chemistry: past, present and future directions illustrated by reference to the on-line, on-stream and off-line determination of trace metals in zinc plant electrolyte by voltammetric and potentiometric techniques

The millennium being celebrated this year coincides with the 200th anniversary of the birth of practical electrochemistry made possible via Volta’s publication of the battery in the year 1800. The analytical chemists at the beginning of the 19th century were very quick to take advantage of this newly reported device and the first qualitative electrochemical determination of copper rapidly followed this pioneering discovery. In the last 200 years, electrochemical analysis, in its various forms, has been undertaken routinely in countless laboratories all over the world. However, in view of the long and distinguished history of the discipline, and some limitations that have been identified at the time of the celebration of the millennium, electrochemical analysis is regarded in some quarters as being a mature and conservative discipline whose importance in the future, when faced with severe competition from newly emerging alternative analytical techniques, is somewhat unclear. In this paper, an overview of past and present developments in electroanalytical chemistry and the possible future status of the technique is presented. In particular, emphasis is given to describing applications relevant to the also very mature field of electrowinning of zinc from plant electrolyte. This overview encompasses the author’s 25 years’ experience in developing polarographic, stripping voltammetric, adsorptive stripping voltammetric and ion-selective electrode (ISE) methods of analysis in on-line, on-stream and off-line modes for the determination of elements such as Cd, Pb, Ge, Sb (oxidation states (III) and (V)), Co, Ni, Zn, Fe, (oxidation states (II) and (III)), Tl, As (total) and Cu in zinc plant electrolyte. Developments that may contribute to an important future for analytical voltammetry are also considered as are limitations that could inhibit the extent of practical use of these electroanalytical techniques in the 21st century.     

Radical mediated synthesis of 6-arylphenanthridines via benzotriazole ring-opening

Lithiation of diarylbenzotriazol-1-ylmethanes followed by addition of copper( I ) iodide gave 6-arylphenanthridine derivatives in moderate yields. When the two aryl groups were the same or contained very different electron densities, only one product was obtained. However, when the two aryl groups exhibited electron densities of similar magnitude, two isomers were afforded. According to the substituent effect, we believe that the reactions proceed via radical intermediates formed by copper( I ) iodide.     

Generation and reactivity of N,N-dimethylaminobenzotriazolylcarbene a new nucleophilic carbene

N,N-Dimethylaminobenzotriazolylcarbene ( 5 ) reacted with phenyl isocyanate in a [1+2+2] cycloaddition and then with nucleophiles to generate various hydantoins 10 in a one-pot procedure. It was also found that this novel carbene reacted with trans-dibenzoylethylene ( 11 ) in a [1+4] cycloaddition, generating 2-dimethylamino-3-benzoyl-5-phenylfuran ( 13 ) and 2-phenyl-3-[benzotriazol-1-yl]-4-benzoylfuran ( 14 ) whose structures were confirmed by ¹H-¹³C long range correlations as well as the structure of furan 14 being confirmed by X-ray crystallography.     

Rhodathiaboranes with `anomalous' electron counts: synthesis, structure and reactivity

Analysis of the structures of 8,8-(PPh₃)₂-8,7-nido-RhSB₉H₁₀ and 9,9-(PPh₃)₂-9,7,8-nido-RhC₂B₈H₁₁ by RMS misfit calculations has confirmed that these rhodaheteroboranes possess nido 11-vertex cluster geometries in apparent contravention of Wade's rules. However, examination of the molecular structures of both species shows that the {RhP₂} planes are inclined by ca. 66° with respect to the metal-bonded SB₃ or CB₃ faces, and that two weak ortho-CHRh agostic interactions occupy the vacant co-ordination position thereby created. As a consequence of these agostic bonds the Rh atom, and hence the overall cluster, is provided with an additional electron pair, meaning that their nido structures are now fully consistent with Wade's rules. The chelated diphosphine compound 8,8-(dppe)-8,7-nido-RhSB₉H₁₀ is similar to the PPh₃ compound in showing the same agostic bonding. Attempts to prepare a bis-P(OMe)₃ analogue result in ligand scavenging and the formation of 8,8,8-{P(OMe)₃}₃-8,7-nido-RhSB₉H₁₀. Similarly, reaction between Cs[6-arachno-SB₉H₁₂] and RhCl(dmpe)CO does not result in CO loss but in formation of 8,8-(dmpe)-8-(CO)-8,7-nido-RhSB₉H₁₀, shown to exist as a mixture of two of three possible rotamers. Deprotonation of 8,8-(PPh₃)₂-8,7-nido-RhSB₉H₁₀ and 8,8-(dppe)-8,7-nido-RhSB₉H₁₀ with MeLi yields the anions [1,1-(PPh₃)₂-1,2-closo-RhSB₉H₉]⁻ and [1,1-dppe-1,2-closo-RhSB₉H₉]⁻, respectively, with octadecahedral cage structures. It is argued that anion formation causes the agostic bonding to be `switched-off' and results in the cluster adopting the closo architecture predicted by Wade's rules. This structural change is fully reversible on reprotonation, and if reprotonation of [1,1-(dppe)-1,2-closo-RhSB₉H₉]⁻ is carried out in MeCN, the product 8,8-(dppe)-8-(MeCN)-8,7-nido-RhSB₉H₁₀ forms. Interestingly, 8,8-(dppe)-8-(MeCN)-8,7-nido-RhSB₉H₁₀ reconverts to 8,8-(dppe)-8,7-nido-RhSB₉H₁₀ on standing in CDCl₃, suggesting that the agostic bonding is sufficiently strong to displace co-ordinated MeCN. All new compounds are fully characterised by multinuclear NMR spectroscopy and, in many cases, by single crystal X-ray diffraction.     

Mixed valence gold chemistry: Stepwise oxidation of a cyclic trigold(I) complex

Oxidation of the cyclic complex Au₃(CH₃OCNCH₃)₃ by iodine or bromine produces three distinct complexes Au₃(CH₃OCNCH₃)₃X_n (_n = 2,4 or 6, X = Br or I) in which the gold atoms undergo stepwise oxidative halogen addition. The products have been characterized by elemental analysis, molecular weight determinations, proton magnetic resonance spectra and IR spectra. The complexes with n = 4 or 2 undergo spontaneous autodecomposition. In the case of Au₃(CH₃OCNCH₃)₃Br₄ this decomposition produces gold metal, Au₃(CH₃OC NCH₃)₃Br₆, methyl bromide, and methyl isocyanate in an extremely clean reaction.