In vitro and in vivo metabolism studies of dimethazine

The use of anabolic steroids is prohibited in sports. Effective control is done by monitoring their metabolites in urine samples collected from athletes. Ethical objections however restrict the use of designer steroids in human administration studies. To overcome these problems alternative in vitro and in vivo models were developed to identify metabolites and to assure a fast response by anti‐doping laboratories to evolutions on the steroid market. In this study human liver microsomes and an uPA^+/+‐SCID chimeric mouse model were used to elucidate the metabolism of a steroid product called ‘Xtreme DMZ’. This product contains the designer steroid dimethazine (DMZ), which consists of two methasterone molecules linked by an azine group. In the performed stability study, degradation from dimethazine to methasterone was observed. By a combination of LC‐High Resolution Mass Spectrometry (HRMS) and GC‐MS(/MS) analysis methasterone and six other dimethazine metabolites (M1–M6), which are all methasterone metabolites, could be detected besides the parent compound in both models. The phase II metabolism of dimethazine was also investigated in the mouse urine samples. Only metabolites M1 and M2 were exclusively detected in the glucuro‐conjugated fraction; all other compounds were also found in the free fraction. For effective control of DMZ misuse in doping control samples, screening for methasterone and methasterone metabolites should be sufficient. Copyright © 2016 John Wiley & Sons, Ltd.     

Modeling of the sputtering process of cubic silver halide microcrystals and its relevance in depth profiling by secondary-ion mass spectrometry (SIMS)

Secondary-ion mass spectrometry is frequently used for concentration–depth profiling of macroscopic samples, but it is certainly not a common analytical technique for the analysis of sub-micrometer-size particles. This is because of the additional ion-bombardment-induced artifacts which can occur when a three-dimensional microvolume is sputtered, instead of a flat surface. This paper presents a model of how small cubic photographic Ag(Cl,Br) crystals are eroded under primary-ion bombardment, and the extent to which secondary ions generated at different faces are extracted. The latter is studied by means of the program SIMION, which simulates ion trajectories in complex electrical field systems. It is shown that up to 90% of the secondary ions originating from the side face of a cubic crystal are unable to reach the detector, in contrast with most secondary ions originating from the top face. The angular dependence of the sputtering yield and the elemental ratio of Br/Cl sputtered particles have been calculated by using the well-known computer code TRIM (transport of ions in matter) under some limiting assumptions (possible preferential sputtering is disregarded and a steady-state sputtering process is assumed). The validity of the theoretical model and the calculated results were checked with experimental data. On the basis of the depth profiles presented it is explained why it is still possible to measure an interface inside a cubic volume, even though a group of several hundred crystals is sputtered simultaneously, and even though the orientations of the distinct faces of the cubes relative to the angle of incidence of the primary-ion beam are different.     

Tetranuclear d-f Metallostars: Synthesis, Relaxometric, and Luminescent Properties

A novel ditopic ligand DTPA-ph-phen, based on 1,10-phenanthroline and diethylenetriaminepentaacetic acid (DTPA) units, has been designed and fully characterized by (1)H, (13)C, and 2D-COSY NMR spectroscopy, IR and electrospray ionization mass spectrometry (ESI-MS) techniques. The DTPA core of the ligand specifically binds Ln(III) ions (Ln = Eu, Gd) resulting in formation of the [Ln{DTPA-ph-phen}(H(2)O)](-) complex. The photophysical properties of the Eu(III) compound have been investigated, and the complex shows characteristic red luminescence with an overall quantum yield of 2.2%. Reaction of [Gd{DTPA-ph-phen}(H(2)O)](-) with Ru(II) leads to further self-assembly into a heterobimetallic metallostar complex containing Gd(III) and Ru(II) in a 3:1 ratio. This tetranuclear [(Gd{DTPA-ph-phen})(3)(H(2)O)(3)Ru](-) complex (Gd(3)Ru), formed by the coordination of Ru(II) to the 1,10-phenanthroline unit, has been characterized by a range of experimental techniques and evaluated toward its feasibility as a potential bimodal optical/MRI agent. The Gd(3)Ru metallostar shows intense metal-to-ligand charge transfer (MLCT) transition resulting in intense light absorption in the visible spectral region. Upon irradiation into this MLCT band at 450 nm, the Gd(3)Ru complex exhibits red broad-band luminescence in the range of 550-800 nm centered at 610 nm with a quantum yield of 4.8%. Proton nuclear magnetic relaxation dispersion (NMRD) measurements indicate that the Gd(3)Ru complex exhibits an enhanced relaxivity value r(1) of 36.0 s(-1) mM(-1) per metallostar molecule at 20 MHz and 310 K. The ability of the complex to noncovalently bind to human serum albumin (HSA) was investigated, but no significant interaction was detected.     

Multimethod 3D characterization of natural plate-like nanoparticles: shape effects on equivalent size measurements

The fundamental properties and processes that govern nanoparticle behavior in colloidal dispersions are critical to predict their performance in applications and also their environmental and health implications. Illite is a platy clay mineral that is present in large amounts in aquatic environments and can be used as a model natural particle for environmental risk assessment. However, the high-aspect ratio of illite makes conventional analysis, usually assuming a spherical size, insufficient for the assessment of shape-dependent properties. In the current paper, a multimethod characterization of a suspension of illite particles was done using atomic force microscopy, scanning electron microscopy, dynamic light scattering (DLS), nanoparticle tracking analysis, differential centrifugal sedimentation, and centrifugal-field flow fractionation coupled to multiangle light scattering and DLS. The relation between the different measurands was investigated, and the effect of the shape on the equivalent particle size was reported. While some of the used techniques are capable of assessing the aspect ratio of illite, the results confirm the need for multiple techniques and analysis of different types of measurands especially for high-aspect-ratio particles.     

A Synthetic Lectin for O‐Linked β‐N‐Acetylglucosamine

Changing employment : Receptor 1 binds β‐N‐acetylglucosaminyl (β‐GlcNAc) up to 100 times more strongly than it does glucose. This synthetic lectin shows affinities similar to wheat germ agglutinin (WGA), a natural lectin used to bind GlcNAc. Remarkably, 1 is more selective than WGA. It favors especially the glycoside unit in glycopeptide 2 , a model of the serine‐O‐GlcNAc posttranslational protein modification.

     

Alignment of high resolution magic angle spinning magnetic resonance spectra using warping methods

The peaks of magnetic resonance (MR) spectra can be shifted due to variations in physiological and experimental conditions, and correcting for misaligned peaks is an important part of data processing prior to multivariate analysis. In this paper, five warping algorithms (icoshift, COW, fastpa, VPdtw and PTW) are compared for their feasibility in aligning spectral peaks in three sets of high resolution magic angle spinning (HR-MAS) MR spectra with different degrees of misalignments, and their merits are discussed. In addition, extraction of information that might be present in the shifts is examined, both for simulated data and the real MR spectra. The generic evaluation methodology employs a number of frequently used quality criteria for evaluation of the alignments, together with PLS-DA to assess the influence of alignment on the classification outcome.Peak alignment greatly improved the internal similarity of the data sets. Especially icoshift and COW seem suitable for aligning HR-MAS MR spectra, possibly because they perform alignment segment-wise. The choice of reference spectrum can influence the alignment result, and it is advisable to test several references. Information from the peak shifts was extracted, and in one case cancer samples were successfully discriminated from normal tissue based on shift information only. Based on these findings, general recommendations for alignment of HR-MAS MRS data are presented. Where possible, observations are generalized to other data types (e.g. chromatographic data).     

Quantum vacuum magnetic birefringence

From a series of M?ssbauer measurements performed on a single crystal of FePSe₃, we have observed the effect of electromagnetically induced transparency (EIT) in a second nuclear system, after a first experiment using the mineral siderite FeCO₃. When the condition of nuclear level crossing was fulfilled, an obvious deficit in absorption was observed at the point of level crossing. This reduced absorption cannot be ascribed to saturation effects because of the specific geometry of the measurement. We conclude that the observed deficit in absorption is due to coherence and interference effects.     

Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K_a≈20 000 m ^?1, whereas the other one binds an O‐GlcNAcylated peptide with K_a≈70 000 m ^?1. These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts.