Rapid synthesis of acyl transfer auxiliaries for cysteine-free native glycopeptide ligation

[reaction: see text] Rapid, facile routes to the TFA-cleavable 4,5,6-trimethoxy-2-mercaptobenzyl and 1-(2,4-dimethoxyphenyl)-2-mercaptoethyl classes of auxiliaries for cysteine-free native chemical ligation are described. Rapid synthesis, coupled with mild cleavage conditions will undoubtedly broaden the utility of such auxiliaries, particularly where chemically fragile peptide modifications such as glycosylation are present.     

Theoretical investigations into the intermediacy of chlorinated vinylcobalamins in the reductive dehalogenation of chlorinated ethylenes

The reductive dehalogenation of perchloroethylene and trichloroethylene by vitamin B(12) produces approximately 95% (Z)-dichloroethylene (DCE) and small amounts of (E)-DCE and 1,1-DCE, which are further reduced to ethylene and ethane. Chloroacetylene and acetylene have been detected as intermediates, but not dichloroacetylene. Organocobalamins (RCbls) have been proposed to be intermediates in this process. Density functional theory based approaches were employed to investigate the properties of chlorinated vinylcobalamins and chlorinated vinyl radicals. They reveal that all vinyl radicals studied have reduction potentials more positive (E degrees >or= -0.49) than that of the Co(II)/Co(I) couple of B(12) (E degrees = -0.61 V), indicating that any (chlorinated) vinyl radicals formed in the reductive dehalogenation process should be reduced to the corresponding anions by cob(I)alamin in competition with their combination with Co(II) to yield the corresponding vinylcobalamins. The computed Co-C homolytic bond dissociation enthalpies (BDEs) of the latter complexes range from 33.4 to 45.8 kcal/mol. The substituent effects on the BDEs are affected by the stabilities of the vinyl radicals as well as steric interactions between (Z)-chloro substituents and the corrin ring. The calculated E degrees values of the cobalamin models were within approximately 200 mV of one another since electron attachment is to a corrin ring pi-orbital, whose energy is relatively unaffected by chloride substitution of the vinyl ligand, and all were >500 mV more negative than that of the Co(II)/Co(I) couple of B(12). Reduction of the base-off forms of vinyl- and chlorovinylcobalamin models also involves the corrin pi* orbital, but reduction of the base-off dichlorovinyl- and trichlorovinylcobalamin models occurs with electron attachment to the sigma(Co)(-)(C*) orbital, yielding calculated E degrees values more positive than that of the calculated Co(II)/Co(I) couple of B(12). Thus, cob(I)alamin is expected to reduce these base-off vinyl-Cbls. Heterolytic cleavage of the Co-C bonds is much more favorable than homolysis (>21 kcal/mol) and is significantly more exergonic when coupled to chloride elimination.     

Molecular recognition and conductance in crown ethers

Crown ethers have the remarkable property of recognizing and binding specific metal cations in complex mixtures. We propose to combine molecular recognition with molecular electric conductance. The question we address is: can the event of binding a cation be sensed by a change in conductance? Specifically, we study a short molecular wire (MW) containing a crown-6 molecule connected via sulfur atoms to two gold atomic wires acting as metallic leads. Upon binding a cation, the density of states of the system is only slightly affected. This reflects the fact that the cation binding is largely electrostatic in nature and is accompanied by little electronic reorganization. Yet, the cationic binding does significantly lower conductance. We also identify strong interference affecting the conductance. A striking feature is the insensitivity of conductance to the type of ligand with the exception of the proton.     

Conformational analysis—II: A lanthanide-induced shift nmr and theoretical study of bicyclo [3.1.0] hexan-3-one and adamantanone

The solution conformation of bicyclo [3.1.0] hexan-3-one has been obtained by the use of the shifts induced in its ¹H and ¹³C NMR by Yb(fod)₃. Refinement of the angle of pucker, ∝, of the 5-membered ring indicates that the molecule adopts a flattened boat conformation with ∝ = 195°. This prediction is supported by ab initio, STO-3G, calculations on the isolated molecule. Use of a two- or four-site model for lanthanide-substrate complexing adequately reproduces the experimental data whereas a one-site binding model is unsatisfactory. The importance of multi-site binding is further emphasised by results for the C_2v-symmetric ketone, adamantanone, where only a four-site model gives satisfactory agreement between observed and calculated lanthanide-induced shifts.     

Preparation and X-ray crystal structures of mixed ligand complexes containing the S3N ligand

Reaction of Hg(S₇N)₂ with cis- PtCl₂(PR₃)₂ (PR₃ = PPh₃, PPh₂Me, PPHMe₂, PEt₃) in the presence of Na[PF₆] gives [Pt(S₃N)(PR₃)₂][PF₆] in 32–46% yield. The complexes have been characterized by IR, NMR and microanalyses. The X-ray crystal structures of two examples (PR₃ = PPh₂Me and PEt₃) show that the S₃N⁻ ligand coordinates in a bidentate fashion via two sulphur atoms.     

The high resolution mass spectrum of 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-glucopyranose

2-Acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-glucopyranose (I), and its analogs specifically mono (trideuterioacetylated) at O-1 (III), at N-2 (II), at O-4 (IV) and at O-6 (V), have been examined by high-resolution mass spectrometry. From the elemental compositions of the fragment ions, the mass-number shifts resulting from deuterium incorporation and analysis of metastable transitions, it has been possible to specify in detail the fragmentation pathways undergone by this molecule. The principal degradations of I proceed by initial rapid decomposition of the molecular ion (whose intensity is insignificant) by three routes: (i) by loss of the C-1 acetoxyl group as a radical to give the glycosyl cation (a), (ii) by loss of the 1-acetyl group as a radical to give an acyclic ion m/e 346 (b) and (iii) by loss of a C-6 fragment and acetic acid derived from the 3-acetate group to give m/e 241 (c).     

Critical factors for high-performance physically adsorbed (dynamic) polymeric wall coatings for capillary electrophoresis of DNA

Physically adsorbed (dynamic) polymeric wall coatings for microchannel electrophoresis have distinct advantages over covalently linked coatings. In order to determine the critical factors that control the formation of dynamic wall coatings, we have created a set of model polymers and copolymers based on N,N-dimethylacrylamide (DMA) and N,N-diethylacrylamide (DEA), and studied their adsorption behavior from aqueous solution as well as their performance for microchannel electrophoresis of DNA. This study is revealing in terms of the polymer properties that help create an "ideal" wall coating. Our measurements indicate that the chemical nature of the coating polymer strongly impacts its electroosmotic flow (EOF) suppression capabilities. Additionally, we find that a critical polymer chain length is required for polymers of this type to perform effectively as microchannel wall coatings. The effective mobilities of double-stranded (dsDNA) fragments within dynamically coated capillaries were determined in order to correlate polymer hydrophobicity with separation performance. Even for dsDNA, which is not expected to be a strongly adsorbing analyte, wall coating hydrophobicity has a deleterious influence on separation performance.     

The infrared spectra (600-150 cm−1 of pyridine N-oxide complexes of metal(II) halides and mixed-ligand (pyridine N-oxide—dimethylsulphoxide) complexes of copper(II) halides

The infrared spectra of the complexes [M(pyO)(H₂O)Cl₂] (M = Mn, Fe, Co, Ni, Cu; pyO = pyridine N-oxide) have been determined. Assignments of ν M-Opy, νM-OH₂ and ν M-Cl are made by observing the effects of deuterating the coordinated pyO and H₂O and replacing chloride by bromide in the Mn(II) complex. Assignments of metal—ligand modes in the mixed ligand complexes [M(pyO)(dmso)X₂] (dmso = dimethylsulphoxide) are made by comparison with the spectra of (ML₂X₂] (L = pyO, dmso) and by observing the effects of deuteration of pyO and dmso. Structural aspects of the spectra are discussed.     

Aging of poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene)/toluene solutions and subsequent effects on luminescence behavior of cast films

Morphological effects in luminescence properties of a representative semiconducting polymer, poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV), has recently attracted much attention. Previous studies indicated that short-term heat treatment of solution-cast MEH-PPV films may result in the formation of mesomorphic order that is responsible for the "red" emission around 640 nm, in contrast to the single-chromophore "yellow" emission near 590 nm from the disordered matrix. On the basis of microscopic and spectroscopic evidence for films cast from freshly prepared and aged solutions, here we show that prolonged storage of MEHyellowPPV solutions at room temperature or lower may result in retardation of the thermally induced mesophase formation in the subsequently cast films. According to small-angle neutron scattering and differential scanning calorimetric observations over aged MEH-PPV/toluene solutions, we propose that the suppressed transformation into mesomorphic order is due to further development of nanocrystalline aggregates that serve as physical cross-links among MEH-PPV chains in the solution state upon long-term storage. These solvent-induced nanocrystalline aggregates, however, do not exhibit new spectroscopic features beyond the suppression of "red" emission at 640 nm from the mesomorphic phase.     

Measurement of PCDDs, PCDFs, and non-ortho-PCBs by comprehensive two-dimensional gas chromatography-isotope dilution time-of-flight mass spectrometry (GC x GC-IDTOFMS)

Comprehensive two-dimensional gas chromatography with isotope-dilution time-of-flight mass spectrometry (GC × GC-IDTOFMS) was used to measure polychlorinated dibenzo-p-dioxin (PCDD), polychlorinated dibenzofuran (PCDF), and coplanar polychlorinated biphenyl (cPCB) concentrations in ash, sediment, vegetation, and fish samples. The GC × GC capability was achieved by using a quad jet, dual stage, thermal modulator. Zone compression of the GC peaks from modulation resulted in a significant increase of the signal intensity over classical GC-IDTOFMS. The GC × GC column set used an Rtx-Dioxin 2 phase as the first dimension (¹D) and an Rtx-500 as the second dimension (²D). The chromatographic separation of the 17 PCDD/Fs and the 4 cPCBs was attained in ¹D except for 2,3,7,8-TCDD and CB126 for which deconvoluted ion currents (DIC) were required to be reported separately. The Rtx-500 phase separated the bulk matrix interfering compounds from the target analytes in ²D. The instrumental limit of detection (iLODs) was 0.5 pg for 2,3,7,8-TCDD. The calibration curves showed good correlation coefficients for all the compounds investigated in the concentration range of 0.5–200 pg. GC × GC-IDTOFMS results compared favorably to those from conventional isotope-dilution one-dimensional gas chromatography-high resolution mass spectrometry (GC-IDHRMS). The comprehensive mass analysis of the TOFMS further permitted the identification of other contaminants of concern in the samples.