Mechanism of homogeneously and heterogeneously catalysed Meerwein-Ponndorf-Verley-Oppenauer reactions for the racemisation of secondary alcohols

The mechanism of hydrogen transfer from alcohols to ketones, catalysed by lanthanide(III) isopropoxides or zeolite Beta has been studied. For the lanthanide catalysed reactions, (S)-1-phenyl-(1-(2)H(1))ethanol and acetophenone were used as case studies to determine the reaction pathway for the hydrogen transfer. Upon complete racemisation all deuterium was present at the 1-position, indicating that the reaction exclusively takes place via a carbon-to-carbon hydrogen transfer. Zeolite Beta with different Si/Al ratios was applied in the racemisation of (S)-1-phenylethanol. In this case the racemisation does not proceed via an oxidation/reduction pathway but via elimination of the hydroxy group and its re-addition. This mechanism, however, is not characteristic for all racemisation reactions with zeolite Beta. When 4-tert-butyl cyclohexanone is reduced with this catalyst, a classical MPV reaction takes place exclusively. This demonstrates that zeolite Beta has a substrate dependent reaction pathway.     

Screening, library-assisted identification and validated quantification of 23 benzodiazepines, flumazenil, zaleplone, zolpidem and zopiclone in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization

A liquid chromatographic/mass spectrometric assay with atmospheric pressure chemical ionization (LC/APCI-MS) is presented for fast and reliable screening and identification and also for precise and sensitive quantification in plasma of the 23 benzodiazepines alprazolam, bromazepam, brotizolam, camazepam, chlordiazepoxide, clobazam, clonazepam, diazepam, flunitrazepam, flurazepam, desalkylflurazepam, lorazepam, lormetazepam, medazepam, metaclazepam, midazolam, nitrazepam, nordazepam, oxazepam, prazepam, temazepam and tetrazepam, triazolam, their antagonist flumazenil and the benzodiazepine BZ1 (omega 1) receptor agonists zaleplone, zolpidem and zopiclone. It allows confirmation of the diagnosis of an overdose situation and monitoring of psychiatric patients' compliance. The analytes were isolated from plasma using liquid-liquid extraction and were separated on a Merck LiChroCART column with Superspher 60 RP Select B as the stationary phase. Gradient elution was performed using aqueous ammonium formate and acetonitrile. After screening and identification in the scan mode using the authors' LC/MS library, the analytes were quantified in the selected-ion monitoring mode. The quantification assay was fully validated. It was found to be selective proved to be linear from sub-therapeutic to over therapeutic concentrations for all analytes, except bromazepam. The corresponding reference levels the assay's accuracy and precision data for all studied substances are listed. The accuracy and precision data were within the required limits with the exception of those for bromazepam. The analytes were stable in frozen plasma for at least 1 month. The validated assay was successfully applied to several authentic plasma samples from patients treated or intoxicated with various benzodiazepines or with zaleplone, zolpidem or zopiclone. It has proven to be appropriate for the isolation, separation, screening, identification and quantification of the drugs mentioned above in plasma for clinical toxicology, e.g. in cases of poisoning, and forensic toxicology, e.g. in cases of driving under the influence of drugs.     

Rate constants from the reaction path Hamiltonian. I. Reactive flux simulations for dynamically correct rates

As ab initio electronic structure calculations become more accurate, inherent sources of error in classical transition state theory such as barrier recrossing and tunneling may become major sources of error in calculating rate constants. This paper introduces a general method for diabatically constructing the transverse eigensystem of a reaction path Hamiltonian in systems with many degenerate transverse frequencies. The diabatically constructed reaction path Hamiltonian yields smoothly varying coupling constants that, in turn, facilitate reactive flux calculations. As an example we compute the dynamically corrected rate constant for the chair to boat interconversion of cyclohexane, a system with 48 degrees of freedom and a number of degenerate frequencies. The transmission coefficients obtained from the reactive flux simulations agree with previous results that have been calculated using an empirical potential. Furthermore, the calculated rate constants agree with experimental values. Comparison to variational transition state theory shows that, despite finding the true bottleneck along the reaction pathway, variational transition state theory only accounts for half of the rate constant reduction due to recrossing trajectories.     

An open source protein gel documentation system for proteome analyses

Data organization and data mining represents one of the main challenges for modern high throughput technologies in pharmaceutical chemistry and medical chemistry. The presented open source documentation and analysis system provides an integrated solution (tutorial, setup protocol, sources, executables) aimed at substituting the traditionally used lab-book. The data management solution provided incorporates detailed information about the processing of the gels and the experimental conditions used and includes basic data analysis facilities which can be easily extended. The sample database and User-Interface are available free of charge under the GNU license from http://webber.physik.uni-freiburg.de/~fallerd/tutorial.htm.     

On-line determination of carboxylic acids, aldehydes and ketones by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionisation mass spectrometry after derivatization with 2-nitrophenylhydrazine

2-Nitrophenylhydrazine (2-NPH) is widely used for the derivatization of carboxylic acids, aldehydes and ketones, in industrial and biological samples. These compounds react with 2-NPH to form derivatives, which are separated by high-performance liquid chromatography (HPLC) and detected with diode array detection (DAD). The UV spectra give information about the functionality of the compounds: carboxylic acid or ketone/aldehyde. Most of the eluting compounds in "known" samples are well characterised by the retention time (comparison with those of standards) of the 2-NPH derivative and their UV spectrum. The identification of different unknown 2-NPH derivatives of carboxylic acids, ketones and/or aldehydes, in industrial or biological samples, based on retention time and/or UV spectrum is not sufficient. These unknown 2-NPH compounds can be identified with on-line atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) based on the molecular mass or/and the fragmentation of the derivative. A novel and specific on-line HPLC-DAD-APCI(-)-MS method is described for the determination of carboxylic acids, ketones and aldehydes, after on-line pre-column derivatization with 2-NHP. The fragmentation of different 2-NPH derivatives were investigated and the possibilities of APCI(-)-MS detection were demonstrated by the on-line identification of an unknown derivative, which turned out to be a side product between 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride and 2-NPH in the presence of high concentrations of a cyclic amide in the sample solution.     

Enantioselective synthesis of chiral sulfones by ir-catalyzed asymmetric hydrogenation: a facile approach to the preparation of chiral allylic and homoallylic compounds

A highly efficient and enantioselective Ir-catalyzed hydrogenation of unsaturated sulfones was developed. Chiral cyclic and acyclic sulfones were produced in excellent enantioselectivities (up to 98% ee). Coupled with the Ramberg-B?cklund rearrangement, this reaction offers a novel route to chiral allylic and homoallylic compounds in excellent enantioselectivities (up to 97% ee) and high yields (up to 94%).     

103Rh-NMR-spektroskopischer Nachweis der gemischten Nonahalogenodirhodate(III), [Rh2ClnBr9–n]3−, n = 0–9

¹⁰³Rh NMR Spectroscopic Evidence of Mixed Nonahalogenodirhodates(III), [Rh₂Cl_nBr_9–n]^3?, n = 0–9 On heating a mixture of the tetrabutylammonium salts (TBA)₃[Rh₂Cl₉] and (TBA)₃[Rh₂Br₉] at 60°C in propylenecarbonate the complete system of the mixed nonahalogenodirhodates(III) [Rh₂Cl_nBr_9–n]^3?, n = 0–9 is formed. In the ¹⁰³Rh nmr spectra 40 different species have been detected, 16 with two equivalent ¹⁰³Rh atoms each resulting in one singlet and 24 with inequivalent ¹⁰³Rh atoms each pair giving two resonances. The signals of the geometric isomeres are not resolved. All 64 expected resonances are really observed. By additional measuring of the ¹⁰³Rh nmr spectra of the fractions n = 0–4 separable by ion exchange chromatography on DEAE cellulose, and utilizing characteristic increments of chemical shifts the complete and unambiguous assignment of all signals is achieved.     

Poly (dodecacarborane-siloxanes)

The need for elastomeric polymers which will maintain their elastic properties at high temperatures has led to a wide interest in inorganic-based polymers [l]. The development of carborane-siloxane polymers in the early 1960s was a breakthrough in the search for a high-temperature elastomer. Incorporation of a carborane moiety into the siloxane backbone significantly enhanced the overall thermal stability [2].