Syntheses, structures and intermolecular interactions of tetraorganoammonium, -phosphonium and -stibonium dimethyl- and diphenyltetrahaloantimonates

The syntheses and spectroscopic (NMR, MS) investigations of the antimonates [Ph₄P]⁺[Me₂SbCl₄]⁻ (1), [Me₄Sb]⁺[Me₂SbCl₄]⁻ (2), [Et₄N]⁺[Ph₂SbCl₄]⁻ (3), [Bu₄N]⁺[Ph₂SbCl₄]⁻ (4), [Me₄Sb]⁺[Ph₂SbCl₄]⁻ (5), [Et₃MeSb]⁺[Ph₂SbCl₄]⁻ (6), [Et₄N]⁺[Ph₂SbF₄]⁻ (7) and [Et₄N]⁺[Ph₂SbBr₄]⁻ (8) are reported. Halogen scrambling reactions of Et₄NBr or Ph₄EBr (E = P, Sb) with R₂SbCl₃ (R = Me, Ph) produce mixtures of compounds from which crystals of [Et₄N]⁺[Ph₂SbBr_1.24Cl_2.76]⁻ (9), [Et₄N]⁺[Ph₂SbBr_2.92Cl_1.08]⁻ (10) or [Ph₄Sb]⁺[Me₂SbCl₄]⁻ (11) were isolated. The crystal and molecular structures of 1 and 3-11 are reported.     

Non-adiabatic dynamics of pyrrole: Dependence of deactivation mechanisms on the excitation energy

Non-adiabatic dynamics simulations were performed for pyrrole at time-dependent density functional theory level using the trajectory surface hopping approach. Initial conditions were prepared based on the UV-absorption spectrum so as to simulate monochromatic absorption in three distinct spectral regions. The results showed predominance of the NH-stretch mechanism for excited-state relaxation. With increasing initial energy, however, other mechanisms are activated as well, even though they still occurred for a minor fraction of the trajectories. Dynamics starting at the origin of the absorption spectrum exhibited internal conversion to the ground state with a time constant of 20 fs. In contrast, dynamics starting at higher energies gave rise to much longer time constants for internal conversion near 200 fs.     

Targeted Metabolomics for Biomarker Discovery

Metabolomics is a truly interdisciplinary field of science, which combines analytical chemistry, platform technology, mass spectrometry, and NMR spectroscopy with sophisticated data analysis. Applied to biomarker discovery, it includes aspects of pathobiochemistry, systems biology/medicine, and molecular diagnostics and requires bioinformatics and multivariate statistics. While successfully established in the screening of inborn errors in neonates, metabolomics is now widely used in the characterization and diagnostic research of an ever increasing number of diseases. In this Review we highlight important technical prerequisites as well as recent developments in metabolomics and metabolomics data analysis with special emphasis on their utility in biomarker identification and qualification, as well as targeted metabolomics by employing high‐throughput mass spectrometry.     

Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography–mass spectrometry

In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors’ systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.     

Phase I and II metabolites of speciogynine, a diastereomer of the main Kratom alkaloid mitragynine, identified in rat and human urine by liquid chromatography coupled to low- and high-resolution linear ion trap mass spectrometry

Mitragyna speciosa (Kratom in Thai), a Thai medical plant, is misused as herbal drug of abuse. Besides the most abundant alkaloids mitragynine (MG) and paynantheine (PAY), several other alkaloids were isolated from Kratom leaves, among them the third abundant alkaloid is speciogynine (SG), a diastereomer of MG. The aim of this present study was to identify the phase I and II metabolites of SG in rat urine after the administration of a rather high dose of the pure alkaloid and then to confirm these findings using human urine samples after Kratom use. The applied liquid chromatography coupled to low- and high-resolution mass spectrometry (LC-HRMS-MS) provided detailed information on the structure in the MS(n) mode particularly with high resolution. For the analysis of the human samples, the LC separation had to be improved markedly allowing the separation of SG and its metabolites from its diastereomer MG and its metabolites. In analogy to MG, besides SG, nine phase I and eight phase II metabolites could be identified in rat urine, but only three phase I and five phase II metabolites in human urine. These differences may be caused by the lower SG dose applied by the user of Kratom preparations. SG and its metabolites could be differentiated in the human samples from the diastereomeric MG and its metabolites comparing the different retention times determined after application of the single alkaloids to rats. In addition, some differences in MS(2) and/or MS(3) spectra of the corresponding diastereomers were observed.     

A modular approach towards functional decoration of peptide-polymer nanotapes

Self-assembled peptide-polymer nanotapes of poly(ethylene oxide)-peptide conjugates are modified by a simple amine-azide transfer to create azide-containing nanofibres, which provide a platform for modular functionalization as demonstrated by the introduction of different carboxyl bearing entities to modulate the calcium binding properties of the nanotapes.     

2‐Amino‐8‐(2‐deoxy‐2‐fluoro‐β‐d‐arabinofuranosyl)imidazo[1,2‐a][1,3,5]triazin‐4(8H)‐one monohydrate,a 2′‐deoxyguanosine analogue with an altered Watson–Crick recognition site

The title compound, C₁₀H₁₂FN₅O₄·H₂O, shows an anti glycosyl orientation [χ = −123.1 (2)°]. The 2‐deoxy‐2‐fluoroarabinofuranosyl moiety exhibits a major C2′‐endo sugar puckering (S‐type, C2′‐endo–C1′‐exo, ²T₁), with P = 156.9 (2)° and τ_m = 36.8 (1)°, while in solution a predominantly N conformation of the sugar moiety is observed. The conformation around the exocyclic C4′—C5′ bond is −sc (trans, gauche), with γ = −78.3 (2)°. Both nucleoside and solvent molecules participate in the formation of a three‐dimensional hydrogen‐bonding pattern via intermolecular N—H...O and O—H...O hydrogen bonds; the N atoms of the heterocyclic moiety and the F substituent do not take part in hydrogen bonding.