Identification and structural characterization of the synthetic cannabinoid 3-(1-adamantoyl)-1-pentylindole as an additive in 'herbal incense'

Since the end of 2010, more than 20 synthetic cannabimimetics have been identified in 'Spice' products, demonstrating the enormous dynamic in this field. In an effort to cope with the problem, many countries have already undertaken legal measures by putting some of these compounds under control. Nevertheless, once a number of compounds were scheduled, they were soon replaced by other synthetic cannabinoids. In this article, we report the identification of a new--and due to its substitution pattern rather uncommon--cannabimimetic found in several 'herbal incense' products. The GC-EI mass spectrum first led to misidentification as the alpha-methyl-derivative of JWH-250. However, since both substances show different retention indices, thin-layer chromatography was used to isolate the unknown compound. After application of nuclear magnetic resonance spectroscopy, high-resolution MS and GC-MS/MS techniques, the compound was identified as 3-(1-adamantoyl)-1-pentylindole, a derivative of JWH-018 carrying an adamantoyl moiety instead of a naphthoyl group. This finding supports that the listing of synthetic cannabinoids as prohibited substances triggers the appearance of compounds with uncommon substituents. Moreover, it emphasizes the necessity of being aware of the risk of misidentification when using techniques sometimes providing only limited structural information like GC-MS.     

A new class of bicyclic dicationic salts based on the 7-azoniabicyclo[2.2.1]heptane scaffold

A new class of dicationic ionic salts has been developed based on two 7-azoniabicyclo[2.2.1]heptane moieties and a variable spacer. The construction of the 7-azabicyclo[2.2.1]heptane skeleton and introduction of the two- to ten-atom spacer occurred concurrently in a one-pot reaction. Quaternization and subsequent metathesis afforded the dicationic salts consisting of two linked quaternized bicyclic moieties and bis(trifluoromethylsulfonyl)imide or dicyanamide as counterions. These salts are liquids at room temperature if the spacer length was larger than seven atoms. X-ray diffraction analysis revealed a linear conformation of the spacer and RS/SR stereochemistry of the quaternized nitrogens.     

Variational second order density matrix study of F3-: importance of subspace constraints for size-consistency

Variational second order density matrix theory under "two-positivity" constraints tends to dissociate molecules into unphysical fractionally charged products with too low energies. We aim to construct a qualitatively correct potential energy surface for F(3)(-) by applying subspace energy constraints on mono- and diatomic subspaces of the molecular basis space. Monoatomic subspace constraints do not guarantee correct dissociation: the constraints are thus geometry dependent. Furthermore, the number of subspace constraints needed for correct dissociation does not grow linearly with the number of atoms. The subspace constraints do impose correct chemical properties in the dissociation limit and size-consistency, but the structure of the resulting second order density matrix method does not exactly correspond to a system of noninteracting units.     

A fast and inexpensive procedure for the isolation of synthetic cannabinoids from ‘Spice’ products using a flash chromatography system

In the age of the Internet, the variety of drugs offered online is constantly increasing, and new drugs emerge every month. One group of drugs showing such an enormous increase is that of synthetic cannabinoids. Since their first identification in ‘herbal mixtures’, new structural modifications continue to appear on the market. In order to keep up with this process, toxicological screening methods need to be up to date. This can become extremely difficult if no reference material is available. In this article, a fast and effective way to extract and purify synthetic cannabinoids from ‘herbal mixtures’ is presented. This method opens a new opportunity for a timely reaction by obtaining reference material straight out of the ‘herbal mixtures’ ordered via the Internet. Isolation was carried out on a flash chromatography system with gradient elution on a C18 column using methanol and 0.55 % formic acid as mobile phases. The obtained purity of all compounds exceeded 99 %. In addition to the isolation of single compounds, the method proved to be suitable for the separation of various synthetic cannabinoids in one mixture, including the diastereomers cis- and trans-CP-47,497-C8. This approach for obtaining pure standards of new drugs proved to be effective, inexpensive and much quicker than waiting for the substances to be commercially available as reference material.

Affinity capturing for targeting proteins into micro and nanostructures

Protein immobilization into micro and nanoscaled patterns opens exciting possibilities in fundamental and applied research. Developing efficient capturing techniques while preserving the structural and functional integrity of the proteins on surfaces is a key challenge for surface scientists. In this paper, current techniques for site-specific protein immobilization into engineered surface architectures are reviewed. Fundamental principles for functional protein immobilization on solid supports are discussed and popular affinity-based recognition pairs and their application for capturing proteins into nano and microstructures are presented.     

A kernel‐based method to determine optimal sampling times for the simultaneous estimation of the parameters of rival mathematical models

When several models are proposed for one and the same process, experimental design techniques are available to design optimal discriminatory experiments. However, because the experimental design techniques are model‐based, it is important that the required model predictions are not too uncertain. This uncertainty is determined by the quality of the already available data, since low‐quality data will result in poorly estimated parameters, which on their turn result in uncertain model predictions. Therefore, model discrimination may become more efficient and effective if this uncertainty is reduced first. This can be achieved by performing dedicated experiments, designed to increase the accuracy of the parameter estimates. However, performing such an additional experiment for each rival model may undermine the overall goal of optimal experimental design, which is to minimize the experimental effort. In this article, a kernel‐based method is presented to determine optimal sampling times to simultaneously estimate the parameters of rival models in a single experiment. The method is applied in a case study where nine rival models are defined to describe the kinetics of an enzymatic reaction (glucokinase). The results clearly show that the presented method performs well, and that a compromise experiment is found which is sufficiently informative to improve the overall accuracy of the parameters of all rival models, thus allowing subsequent design of an optimal discriminatory experiment. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

Polymer based RIFS sensing: an approach to the indirect measurement of organic pollutants in water

Organic pollutants in water originating from industrial sources are a major problem. For their detection, the application of thin film polymer transducers is described. The reflectometric interference spectroscopy (RIFS) technique was used as a method of detection. Sampling is achieved by an FIA system which allows the determination of concentrations of hydrocarbons in water. The experimental set-up is outlined in detail. The sensitivities for toluene and different chlorinated hydrocarbons are given. The sensors used show a linear dependence on the analyte concentration over a wide concentration range. The limit of detection achieved with this system is discussed.