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.     

Non-destructive bulk analysis of the Buggenum sword by neutron resonance capture analysis and neutron diffraction

Two neutron based techniques, neutron resonance capture analysis (NRCA) and time-of-flight neutron-diffraction (TOF-ND) have been used to determine the elemental composition and structure of a precious and very well preserved all-metal sword from the Bronze Age. This Buggenum sword was on loan from the National Museum of Antiquities (NMA) in Leiden (NL). NRCA and TOF-ND experiments have been carried out at a number of more or less identical positions of the sword. The tin-bronze ratio and the relative amounts of some minor elements (Sb, As, Ag, In) have been determined. The results of neutron diffraction measurements showed considerable tin-segregation, and clear indications of hardening on the edges of the blade. In addition, radiographs using Bremsstrahlung revealed the construction of the hilt–blade connection. The work was carried out at the EC Joint Research Centre IRMM in Geel (B) and at the ISIS facility of the Rutherford Appleton Laboratory (UK).     

Werkzeug für die Chemische Biologie. Semisynthese

Semisynthetic techniques have greatly contributed to the rapid development of Chemical Biology in recent years. In this regard the semisynthesis of complex modified proteins as well as the selective derivatization of natural products has evolved into more than mere proof‐of‐principle concepts but powerful tools to probe protein functions. This technology provides a solid basis for further investigations on proteomics and qualitative and quantitative cell biology. The interdisciplinary charter bridging chemistry and biology is the hallmark of semisynthesis. It can be expected that its scientific impact will further increase in the future.     

Semisynthese. Chemie mit den Molekülen der Natur

In Semisynthesis complex molecules have to be manipulated in a chemoselective, regioselective, and stereoselective fashion, necessitating smart protective group operations and innovative synthesis development. Key are always easily accessible and suitable starting materials, especially intermediates which can be produced by biotechnological processes. An extensive synthetic construction of drug candidates carries high innovative and intellectual property protection potential, hence multistep semi‐ and even total syntheses are an integral part of modern industrial research and drug development. Not a long time ago, the complexity such realized would have been inconceivable, which profoundly illustrates the progress synthesis methodology has made. Semisynthesis always aims more toward focussed application, and hence its scientific contribution mostly cater to the elucidation of molecular correlations. Especially the study of cellular processes and their quantification will be stimulated in the future. Thereby semisynthesis will continue to bridge the key future areas of synthesis research and chemical biology.     

Electrical detection of coherent nuclear spin oscillations in phosphorus-doped silicon using pulsed ENDOR

We demonstrate the electrical detection of pulsed X-band electron nuclear double resonance (ENDOR) in phosphorus-doped silicon at 5 K. A pulse sequence analogous to Davies ENDOR in conventional electron spin resonance is used to measure the nuclear spin transition frequencies of the (31)P nuclear spins, where the (31)P electron spins are detected electrically via spin-dependent transitions through Si/SiO(2) interface states, thus not relying on a polarization of the electron spin system. In addition, the electrical detection of coherent nuclear spin oscillations is shown, demonstrating the feasibility to electrically read out the spin states of possible nuclear spin qubits.     

Addendum to the paper "Dead-time free measurement of dipole-dipole interactions between electron spins" by M. Pannier, S. Veit, A. Godt, G. Jeschke, and H.W. Spiess [J. Magn. Reson. 142 (2000) 331-340

The development of four-pulse DEER as described, which has been published in the Journal of Magnetic Resonance more than 10 years ago. The corresponding paper is an example where a slight advance, such as adding a refocusing pulse, which in retrospect looks so simple, can have a remarkable impact on an entire field of science. In our case it offered a simple way to exact measurements of distances between defined species in the nanometer range. The current applications are mainly in determining structures of proteins and nucleic acids.