Analysis of a new drug of abuse: Cathinone derivative 1‐(3,4‐dimethoxyphenyl)‐2‐(ethylamino)pentan‐1‐one

Recently, novel psychoactive drugs for human abuse such as amphetamines, phenethylamines, benzofuries, and tryptamines, cathinones have gained high popularity. These designer drugs are mainly sold via online stores as “bath salts” and are labeled “not for human consumption.” Due to the novelty of the compounds, only a little information about pharmacology, toxicology, and the long‐term damage they may cause is available. Moreover, there are only few analytical methods for their identification and analysis. Among new cathinone derivatives, 1‐(3,4‐dimethoxyphenyl)‐2‐(ethylamino)pentan‐1‐one (DL‐4662), became available via an internet shop. A sample of this compound was purchased and investigated. The first aim of our study was an identity check by NMR spectroscopy and gas chromatography with mass spectrometry. As many of the recreational drugs are chiral and are mainly sold as racemates, a further goal of our research was enantioseparation by gas chromatography with mass spectrometry and high‐performance liquid chromatography with UV detection, to prove whether DL‐4662 was traded enantiomerically pure or as racemic mixture. Both chiral separation methods showed the presence of a racemate.     

QuickFF: A program for a quick and easy derivation of force fields for metal‐organic frameworks from ab initio input

QuickFF is a software package to derive accurate force fields for isolated and complex molecular systems in a quick and easy manner. Apart from its general applicability, the program has been designed to generate force fields for metal‐organic frameworks in an automated fashion. The force field parameters for the covalent interaction are derived from ab initio data. The mathematical expression of the covalent energy is kept simple to ensure robustness and to avoid fitting deficiencies as much as possible. The user needs to produce an equilibrium structure and a Hessian matrix for one or more building units. Afterward, a force field is generated for the system using a three‐step method implemented in QuickFF. The first two steps of the methodology are designed to minimize correlations among the force field parameters. In the last step, the parameters are refined by imposing the force field parameters to reproduce the ab initio Hessian matrix in Cartesian coordinate space as accurate as possible. The method is applied on a set of 1000 organic molecules to show the easiness of the software protocol. To illustrate its application to metal‐organic frameworks (MOFs), QuickFF is used to determine force fields for MIL‐53(Al) and MOF‐5. For both materials, accurate force fields were already generated in literature but they requested a lot of manual interventions. QuickFF is a tool that can easily be used by anyone with a basic knowledge of performing ab initio calculations. As a result, accurate force fields are generated with minimal effort. © 2015 Wiley Periodicals, Inc.     

Some new results on the well-posedness of hyperbolic evolution equations

We summarize some recently obtained results on the well-posedness of hyperbolic linear evolution equations. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Formation and stability of prolinol and prolinol ether enamines by NMR: delicate selectivity and reactivity balances and parasitic equilibria

Enamine key intermediates in organocatalysis, derived from aldehydes and prolinol or J?rgensen-Hayashi-type prolinol ether catalysts, were generated in different solvents and investigated by NMR spectroscopy. Depending on the catalyst structure, trends for their formation and amounts are elucidated. For prolinol catalysts, the first enamine detection in situ is presented and the rapid cyclization of the enamine to the oxazolidine ("parasitic equilibrium") is monitored. In the case of diphenylprolinol, this equilibrium is fully shifted to the endo-oxazolidine ("dead end") by the two geminal phenyl rings, most probably because of the Thorpe-Ingold effect. With bulkier and electron-withdrawing aryl rings, however, the enamine is stabilized relative to the oxazolidine, allowing for the parallel detection of the enamine and the oxazolidine. In the case of prolinol ethers, the enamine amounts decrease with increasing sizes of the aryl meta-substituents and the O-protecting group. In addition, for small aldehyde alkyl chains, Z-configured enamines are observed for the first time in solution. Prolinol silyl ether enamines are evidenced to undergo slow desilylation and subsequent rapid oxazolidine formation in DMSO. For unfortunate combinations of aldehydes, catalysts, solvents, and additives, the enamine formation is drastically decelerated but can be screened for by a rapid and facile NMR approach. Altogether, especially by clarifying the delicate balances of catalyst selectivity and reactivity, our NMR spectroscopic findings can be expected to substantially aid synthetically working organic chemists in the optimization of organocatalytic reaction conditions and of prolinol (ether) substitution patterns for enamine catalysis.     

Enantioseparation by chromatographic and electromigration techniques using ligand-exchange as chiral separation principle

This article gives a short overview of the application of the principle of chiral ligand-exchange in HPLC, CE, and CEC. Since its introduction by Davankov, more than thousand articles have appeared in this field. Citing all these papers would extend the scope of this review—it would fill several books. Therefore only some milestones are mentioned in this article and it will focus on our own activities in this field. Some new developments are mentioned, and selected biochemical and biomedical application are presented.     

NMR investigations on the proline-catalyzed aldehyde self-condensation: Mannich mechanism, dienamine detection, and erosion of the aldol addition selectivity

The proline-catalyzed self-condensation of aliphatic aldehydes in DMSO with varying amounts of catalyst was studied by in situ NMR spectroscopy. The reaction profiles and intermediates observed as well as deuteration studies reveal that the proline-catalyzed aldol addition and condensation are competing, but not consecutive, reaction pathways. In addition, the rate-determining step of the condensation is suggested to be the C-C bond formation. Our findings indicate the involvement of two catalyst molecules in the C-C bond formation of the aldol condensation, presumably by the activation of both the aldol acceptor and donor in a Mannich-type pathway. This mechanism is shown to be operative also in the oligomerization of acetaldehyde with high proline amounts, for which the first in situ detection of a proline-derived dienamine was accomplished. In addition, the diastereoselectivity of the aldol addition is evidenced to be time-dependent since it is undermined by the retro-aldolization and the competing irreversible aldol condensation; here NMR reaction profiles can be used as a tool for reaction optimization.     

A classification tree approach for the modeling of competing risks in discrete time

Advances in Data Analysis and Classification - Cause-specific hazard models are a popular tool for the analysis of competing risks data. The classical modeling approach in discrete time consists of...     

Upper and Lower Bounds for the Synchronizer Performance in Systems with Probabilistic Message Loss

Methodology and Computing in Applied Probability - In this paper, we revisit the performance of the α-synchronizer in distributed systems with probabilistic message loss as introduced in...