Optoacoustic monitoring of blood hemoglobin concentration: a pilot clinical study

The optoacoustic technique is noninvasive, has high spatial resolution, and potentially can be used to measure the total hemoglobin concentration ([THb]) continuously and accurately. We performed in vitro measurements in blood and in vivo tests in healthy volunteers. Our clinical protocol included rapid infusion of intravenous saline to simulate rapid change in the [THb] during fluid therapy or surgery. Optoacoustic measurements were made from the wrist area overlying the radial artery for more than 1 h. The amplitude of the optoacoustic signal generated in the radial artery closely followed the [THb] measured directly in concurrently collected blood samples.     

Wavelength dependencies in interferometric measurements of thin protein films

Summary The evaluation of the spectral modulation in reflectance measurements at thin dielectric films allows the characterisation of layers in the m-range. Diode array spectrometers make this technique a useful tool in sensor development. The variation of the optical pathlength in thin films due to change of refractive index or to change of physical thickness of a homogeneous layer has been applied to refractometry and detection of hydrocarbons by polymer swelling. More recently, the monitoring of solid-phase affinity reactions, like immunoassays has successfully been demonstrated. While the homogeneous layer concept is useful for data evaluation in the first two cases, it has its limitations for the treatment of adlayer formation as in the latter case. This is discussed with respect to results from affinity reactions carried out at optically different interference layers.Dedicated to Professor Dr. Wilhelm Fresenius on the occasion of his 80th birthday     

Covalent strategy for immobilization of DNA-microspots suitable for microarrays with label-free and time-resolved optical detection of hybridization

Sequence-specific detection and quantification of nucleic acids are central steps in many molecular biology procedures which have also been transferred to chip-based procedures. Hybridization-based assays can be used to quantify and discriminate between DNA target sequences down to the level of single base mismatches. Arrays of DNA probes immobilized on a support enable simultaneous testing of multiple sequences of a single sample. DNA arrays can be produced either by in-situ synthesis of oligonucleotides or by immobilization of pre-assembled DNA probes. Covalent and directed immobilization improves the reproducibility and stability of DNA arrays. This is especially interesting with repeated use of transducers or chips. Procedures are described for effective covalent immobilization of pre-assembled amino-linked oligonucleotides, by use of ink-jet techniques, on a modified and heated glass surface, with addressable surface areas ranging from 0.01 mm2 to a few mm2. Almost immediate evaporation of the spotted droplets on the heated surfaces leads to very high surface hybridization capacities. The surfaces are suitable for use with a label-free detection method - reflectometric interference spectroscopy (RIfS). It is shown that hybridization capacity and non-specific interaction at these DNA-surfaces can be characterized by use of RIfS. With a consumption of less than 80 ng mm(-2) oligonucleotide and a specific hybridization capacity of more than 300 fmol mm(-2), the activated aminodextran procedure was usually suitable for setting up a DNA array with label-free detection. Non-specific interactions with random oligomers or protein (ovalbumin) were low. Up to 150 repeated regenerations (stripping) of the surfaces by acid treatment and denaturing agents, and 50 days of storage, have been possible without significant loss of hybridization capacity.     

Synthesis of (±)‐Nephromopsinic, (−)‐Phaseolinic,and (−)‐Dihydropertusaric Acids

The formal syntheses of (±)‐nephromopsinic acid, (−)‐phaseolinic acid, and the first total synthesis of (−)‐dihydropertusaric acid from (±)‐ and (−)‐7‐oxabicyclo[2.2.1]hept‐5‐en‐2‐one are described. These syntheses take advantage of a previously reported radical rearrangement (1,2‐acyl migration). A remarkable iodide‐mediated cleavage of a bicyclic system, followed by the introduction of the γ‐chains via a mixed Kolbe electrolysis, are the key steps of these syntheses. This approach is general and could be applied for the preparation of all kinds of paraconic acids with excellent control of the stereochemistry.     

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.