A Functional Role for Aβ in Metal Homeostasis? N‐Truncation and High‐Affinity Copper Binding

Accumulation of the β‐amyloid (Aβ) peptide in extracellular senile plaques rich in copper and zinc is a defining pathological feature of Alzheimer′s disease (AD). The Aβ1–x (x=16/28/40/42) peptides have been the primary focus of Cu^II binding studies for more than 15 years; however, the N‐truncated Aβ4–42 peptide is a major Aβ isoform detected in both healthy and diseased brains, and it contains a novel N‐terminal FRH sequence. Proteins with His at the third position are known to bind Cu^II avidly, with conditional log K values at pH 7.4 in the range of 11.0–14.6, which is much higher than that determined for Aβ1–x peptides. By using Aβ4–16 as a model, it was demonstrated that its FRH sequence stoichiometrically binds Cu^II with a conditional K_d value of 3×10⁻¹⁴ M at pH 7.4, and that both Aβ4–16 and Aβ4–42 possess negligible redox activity. Combined with the predominance of Aβ4–42 in the brain, our results suggest a physiological role for this isoform in metal homeostasis within the central nervous system.     

N-Nitrosodimethylamine Contamination in the Metformin Finished Products

A GC–MS/MS method with EI ionization was developed and validated to detect and quantify N-nitrosodimethylamine (NDMA) and seven other nitrosamines in 105 samples of metformin tablets from 13 different manufactures. Good linearity for each compound was demonstrated over the calibration range of 0.5–9.5 ng/mL. The assay for all substances was accurate and precise. NDMA was not detected in the acquired active pharmaceutical ingredient (API); however, NDMA was detected in 64 (85.3%) and 22 (91.7%) of the finished product and prolonged finished product samples, respectively. European Medicines Agency recommends the maximum allowed limit of 0.032 ppm in the metformin products. Hence, 28 finished products and 7 pronged dosage products were found to exceed the acceptable limit of daily intake of NDMA contamination. The implications of our findings for the testing of pharmaceutical products are discussed.     

Effect of the peptide secondary structure on the peptide amphiphile supramolecular structure and interactions

Bottom-up fabrication of self-assembled nanomaterials requires control over forces and interactions between building blocks. We report here on the formation and architecture of supramolecular structures constructed from two different peptide amphiphiles. Inclusion of four alanines between a 16-mer peptide and a 16 carbon long aliphatic tail resulted in a secondary structure shift of the peptide headgroups from α helices to β sheets. A concomitant shift in self-assembled morphology from nanoribbons to core-shell worm-like micelles was observed by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). In the presence of divalent magnesium ions, these a priori formed supramolecular structures interacted in distinct manners, highlighting the importance of peptide amphiphile design in self-assembly.     

Charge-sensitive vibrational modes in the (EDT-TTF-OX)2AsF6 chiral molecular conductors

Infrared and Raman spectra of three chiral molecular conductors (EDT-TTF-OX)₂AsF₆, comprising of two salts based on enantiopure EDT-TTF-OX donor molecules and one based on their racemic mixture, have been measured as a function of temperature. In the frequency range of the C=C stretching vibrations of EDT-TTF-OX, charge-sensitive modes are identified based on theoretical calculations for neutral and oxidized EDT-TTF-OX using density functional theory (DFT) methods. The positions of C=C stretching modes in both Raman and infrared spectra of the (EDT-TTF-OX)₂AsF₆ materials are analyzed assuming a linear relationship between the frequency and charge of the molecule. The charge density on the EDTTTF-OX donor molecule is estimated to be +0.5 in all investigated materials and does not change with temperature. Therefore we suggest, that M-I transition observed in (EDT-TTF-OX)₂AsF₆ chiral molecular conductors at low temperature is not related to the charge ordering mechanism.     

Determination of azaarenes in oils using the LC‐APCI‐MS/MS technique: New environmental toxicant in food oils

A novel method to determine of azaarenes in refined and cold‐pressed vegetable oils and animal fats is reported. The method may be used to determine eight most important acridine derivatives (benz[a]acridine, dibenz[a,i]acridine, benz[c]acridine, dibenz[a,j]acridine, 7,9‐dimethylbenz[c]acridine, dibenz[a,h]acridine, dibenz[a,c]acridine, dibenz[c,h]acridine) at a high sensitivity (LOQ in the 2–25 ng kg^?1 range), high analyte recovery rates (70.7–98.7%), sufficient linearity within the studied concentration range (r > 0.97). The method is fast, simple, and needs no expensive clean‐up procedures to successfully determine the analytes. Azaarene concentration in the studied oil samples ranged from 2 to 250 ng kg^?1. Benz[a]acridine and dibenz[a,j]acridine were the compounds found most commonly and at the highest concentrations. The observed concentrations most probably reflected levels of environmental contamination of raw materials used to produce the analyzed oil/fat samples.     

Fractional quasiexcitons in incompressible electron liquids

A new kind of many-body excitonic state composed of fractionally charged constituents is introduced. The constituents are a trion (X^-) embedded in an incompressible electron liquid and Laughlin quasiholes (QH's). Laughlin electron–trion correlations lead to an effective trion charge of -e/3. This many-body excitation is called “quasiexciton” and denoted by to distinguish it from a normal trion. The can bind one or two (e/3)-charged QH's, giving a neutral or a positive . The energy spectra and photoluminescence from radiative quasiexciton decay are studied numerically and interpreted using a generalized composite Fermion model of the e–X^- fluid.     

Evaluating paper degradation progress. Cross-linking between chromatographic, spectroscopic and chemical results

The study presents an overview of the chromatographic (SEC), spectroscopic (FTIR, UV/VIS), viscometric (DP) and chemical methods (titration, pH) used for the evaluation of the degradation progress of various kinds of paper under various conditions. The methods were chosen to follow different routes of paper degradation. Model paper samples represented boundary paper types from pure cellulose cotton paper, through softwood to low quality acidic, sized groundwood paper The accelerated ageing conditions were adjusted to achieve maximum effect (climatic chamber RH 59%, 90^oC) and also to mimic the environment inside books (closed vials). The results were settled on the literature data on the degradation mechanisms and compared in terms of the paper types and ageing conditions. The estimators of coupled de-polymerisation and oxidation have been proposed based on the correlation between SEC, UV/VIS and titrative coppper number determination. The overall oxidation index derived from FTIR results was shown to correlate with the summary –CHO and –COOH concentration determined by titrative methods.     

Controlling Emissive Properties by Intramolecular Hydrogen Bonds: Alkyl and Aryl meso-Substituted Porphycenes

Porphycene, a porphyrin isomer, is an efficient fluorophore. However, four-fold meso substitution with alkyl groups decreases the fluorescence quantum yield by orders of magnitude. For aryl substituents, this effect is small. To explain this difference, we have synthesized and studied a mixed aryl-alkyl-substituted compound, 9,20-diphenyl-10,19-dimethylporphycene, as well as the 9,20-diphenyl and 9,20-dimethyl derivatives. Analysis of the structural, spectroscopic, and photophysical data of the six porphycenes, combined with quantum chemical calculations, shows a clear correlation between the strength of the intramolecular NH⋅⋅⋅N hydrogen bonds and the efficiency of the radiationless depopulation of the lowest-excited singlet state. This result led us to propose a model in which the delocalization of the inner protons in the cavity of the macrocycle is responsible for the nonradiative deactivation channel. The applicability of the model is confirmed by the literature data for other alkyl- or aryl-substituted porphycenes. The finding of a correlation between structural and emissive characteristics enables a rational design of porphycenes with desired photophysical properties.     

New Insights into Cinchonine–Aluminium Complexes and Their Application as Chiral Building Blocks: Unprecedented Ligand‐Exchange Processes in the Presence of ZnR2 Compounds

Previous studies have demonstrated that [(CN)₂AlCl] and [R₂Al(μ‐CN)]₂ (CN=deprotonated cinchonine) complexes can effectively act as chiral, semirigid, N,N‐ditopic metalloligands for Zn‐containing nodes, and provide viable means for constructing new, homochiral, heterometallic, coordination polymers of zigzag and helical topologies. These findings have prompted further investigations on the organometallic analogues of the formula [(CN)₂AlR], anticipating their utility as N,N‐metalloligands for ZnR₂ units. Surprisingly, reactions of [(CN)₂AlMe]‐type metalloligands with ZnR₂ compounds (R=Me or Et) revealed unprecedented ligand‐exchange processes, including zinc‐to‐aluminium and aluminium‐to‐zinc transmetalations of alkyl groups. The molecular and crystal structure of the resulting compounds was determined by X‐ray diffraction analysis. From the reaction of [(CN)₂AlMe] with ZnMe₂ a new pseudopolymorphic form of a noncovalent porous material based on [Me₂Al(μ‐CN)]₂ molecules was isolated. Strikingly, the analogous reaction involving ZnEt₂ led to the generation of a new chiral 4N‐tetratopic heterometalloligand [(CN)EtAl(μ‐CN)₂ZnEt]. The latter unit was successfully connected by alkyl‐exchanged ZnMe₂ nodes to give an original homochiral heterometallic {[(CN)EtAl(μ‐CN)₂ZnEt]ZnMe₂}_n coordination polymer adopting a snake 1D motif. The outcome of the revealed reactions indicates the complicated multistep reaction route that involves redistribution of cinchonine and alkyl ligands among the Al and Zn centers, and a general reaction scheme is proposed. The results are in strong contrast with the previously studied inorganic–organic [(CN)₂AlCl/ZnCl₂] system, which exclusively affords a helical coordination polymer based on ZnCl₂ nodes and (CN)₂AlCl metalloligands and lacks the exchange of CN ligands.