High repetition rate mid-infrared laser source

An efficient, high-power mid-infrared laser source based on ZnGeP₂ (ZGP) optical parametric oscillator (OPO) is presented. Using a Q-switched Ho:YAG laser as the pump source a total output power of 10.6 W was obtained in the 3–5 μm band at 10 kHz and 8.5 W at 20 kHz. The Ho:YAG laser was pumped by two diode-pumped polarization coupled Tm:YLF lasers. Optical-to-optical efficiency achieved is >8.8% (laser-diode 792 nm to mid-IR 3–5 μm). With a commercial PtSi infrared camera (256×256 pixel focal plane array, 24 μm pitch) the pointing stability of Ho pump, signal and idler beam was measured to be better than 30 μrad. Whilst propagating the OPO beams over 100 m, little absorption for the idler beam was observed, resulting in a significant higher peak-to-peak value of ±22%, whereas the peak-to-peak stability of the signal pulses remained unchanged (±13%). To cite this article: M. Schellhorn et al., C. R. Physique 8 (2007).     

Protective Effect of Dermal Brimonidine Applications Against UV Radiation‐induced Skin Tumors,Epidermal Hyperplasia and Cell Proliferation in the Skin of Hairless Mice

Brimonidine at 0.18%, 1% and 2% concentrations applied topically in hairless mice significantly decreased tumor burden and incidences of erythema, flaking, wrinkling and skin thickening induced by UVR. The unbiased median week to tumor ≥1 mm was increased by the 1% and 2% concentrations. The tumor yield was reduced by all concentrations at week 40 for all tumor sizes but the ≥4 mm tumors with the 0.18% concentration. At week 52, the tumor yield was reduced for all tumor sizes and all brimonidine concentrations. The tumor incidence was reduced by all concentrations at week 40 for all tumor sizes, but the ≥4 mm tumor with the 0.18% concentration and at week 52 for all tumor sizes with the 1% and 2% concentrations and with the 0.18% concentration only for the ≥4 mm tumors. Reductions in ≥4 mm tumor incidences compared to the vehicle control group were 54%, 91% and 86% by week 52 for the 0.18%, 1% and 2% concentrations, respectively. Brimonidine at 2% applied 1 h before or just after UVB irradiation on hairless mice decreased epidermal hyperplasia by 23% and 32% and epithelial cell proliferation by 59% and 64%, respectively, similar to an epidermal growth factor receptor (EGFR) inhibitor.     

Comprehensive and High-Throughput Exploration of Chemical Space Using Broadband 19F NMR-Based Screening

Fragment-based lead discovery has become a fundamental approach to identify ligands that efficiently interact with disease-relevant targets. Among the numerous screening techniques, fluorine-detected NMR has gained popularity owing to its high sensitivity, robustness, and ease of use. To effectively explore chemical space, a universal NMR experiment, a rationally designed fragment library, and a sample composition optimized for a maximal number of compounds and minimal measurement time are required. Here, we introduce a comprehensive method that enabled the efficient assembly of a high-quality and diverse library containing nearly 4000 fragments and screening for target-specific binders within days. At the core of the approach is a novel broadband relaxation-edited NMR experiment that covers the entire chemical shift range of drug-like ¹⁹F motifs in a single measurement. Our approach facilitates the identification of diverse binders and the fast ligandability assessment of new targets.     

Calcifications in human osteoarthritic articular cartilage: ex vivo assessment of calcium compounds using XANES spectroscopy

Calcium (Ca²⁺)‐containing crystals (CCs), including basic Ca²⁺ phosphate (BCP) and Ca²⁺ pyrophosphate dihydrate (CPPD) crystals, are associated with severe forms of osteoarthritis (OA). Growing evidence supports a role for abnormal articular cartilage mineralization in the pathogenesis of OA. However, the role of Ca²⁺ compounds in this mineralization process remains poorly understood. Six patients, who underwent total knee joint replacement for primary OA, have been considered in this study. Cartilage from femoral condyles and tibial plateaus in the medial and lateral compartments was collected as 1 mm‐thick slices cut tangentially to the articular surface. First, CCs presence and biochemical composition were assessed using Fourier transform infrared spectroscopy (FT‐IR). Next, Ca²⁺ compound biochemical form was further assessed using X‐ray absorption spectroscopy (XAS) performed at the Ca²⁺K‐absorption edge. Overall, 12 cartilage samples were assessed. Using FT‐IR, BCP and CPPD crystals were detected in four and three out of 12 samples, respectively. Ca²⁺ compound biochemical forms differed between areas with versus without CCs, when compared using XAS. The complete set of data shows that XANES spectroscopy can be used to accurately characterize sparse CCs in human OA cartilage. It is found that Ca²⁺ compounds differ between calcified and non‐calcified cartilage areas. In calcified areas they appear to be mainly involved in calcifications, namely Ca²⁺ crystals.     

Thiophene based europium β-diketonate complexes: effect of the ligand structure on the emission quantum yield

The synthesis and the molecular and photophysical characterization, together with solid state and solution structure analysis, of a series of europium complexes based on β-diketonate ligands are reported. The Eu(III) complex emission, specifically its photoluminescence quantum yield (PL-QY), can be tuned by changing ligands which finely modifies the environment of the metal ion. Steady-state and time-resolved emission spectroscopy and overall PL-QY measurements are reported and related to geometrical features observed in crystal structures of some selected compounds. Moreover, paramagnetic NMR, based on the analogous complexes with other lanthanides, are use to demonstrate that there is a significant structural reorganization upon dissolution, which justifies the observed differences in the emission properties between solid and solution states. The energy of the triplet levels of the ligands and the occurrence of nonradiative deactivation processes clearly account for the luminescence efficiencies of the complexes in the series.     

Simultaneous capillary electrophoresis competitive immunoassay for insulin, glucagon, and islet amyloid polypeptide secretion from mouse islets of Langerhans

A capillary electrophoresis competitive immunoassay was developed for the simultaneous quantitation of insulin, glucagon, and islet amyloid polypeptide (IAPP) secretion from islets of Langerhans. Separation buffers and conditions were optimized for the resolution of fluorescein isothiocyanate (FITC)-labeled glucagon and IAPP immunoassay reagents, which were excited with the 488 nm line of an Ar(+) laser and detected at 520 nm with a photomultiplier tube (PMT). Cy5-labeled insulin immunoassay reagents were excited by a 635 nm laser diode module and detected at 700 nm with a separate PMT. Optimum resolution was achieved with a 20mM carbonate separation buffer at pH 9.0 using a 20 cm effective separation length with an electric field of 500 V/cm. Limits of detection for insulin, glucagon, and IAPP were 2, 3, and 3 nM, respectively. This method was used to monitor the simultaneous secretion of these peptides from as few as 14 islets after incubation in 4, 11, and 20 mM glucose for 6h. For insulin and IAPP, a statistically significant increase in secretion levels was observed, while glucagon levels were significantly reduced in the 4 and 11 mM glucose conditions. To further demonstrate the utility of the assay, the Ca(2+)-dependent secretion of these peptides was demonstrated which agreed with published reports. The ability to examine the secretion of multiple peptides may allow for the determination of regulation of secretory processes within islets of Langerhans.     

N-aryl pyrazoles: DFT calculations of CH acidity and deprotonative metallation using a combination of lithium and zinc amides

A series of N-aryl and N-heteroaryl pyrazoles have been deproto-metallated using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination. Mono-, di-, and tri-iodides have been obtained after subsequent trapping with iodine, depending on the substrate and on the quantity of base used. The results have been discussed in the light of the CH acidities of the substrates, determined both in the gas phase and in THF solution using the DFT B3LYP method.     

Sensitivity and amplitude calibration of a Fourier transform 3D quadrupole ion trap mass spectrometer

With a three-dimensional (3D) quadrupole ion trap running in a Fourier transform operating mode, the detected signal is an image of the collective motion of the confined ions. Consequently, it is assumed that the image signal is the sum of the axial trajectories of the simultaneously confined ions. The resulting frequency spectrum after Fourier transformation comprises frequency peaks at the axial secular frequencies of the confined species according to their mass/charge ratio. With a singly confined species, the maximal amplitude of the image signal is proportional to the amplitude of the secular axial frequency peak. The matrix method is employed to express the axial trajectory sampled at the confinement field period. In that case, the expression of the image signal, as well as its maximal amplitude, is calculated as a function of the trap operating conditions and initial axial positions and axial velocities of the ions. The initial position and velocity distributions are connected to the injection mode. With the steady ion flow injection mode (SIFIM) and an initial phase of the confinement field equal to kπ, the maximal amplitude of the image signal is proportional to either the sum of the initial axial positions or the number of confined ions and the mean value of the initial axial positions. By simulation, amplitude fluctuation of the frequency peak is then calculated for a number of ions ranging between some tens to some thousands of ions injected by SIFIM. The peak amplitude fluctuations induced by the fluctuations of the number of ions are seven times greater than those induced by the fluctuations of the distribution of the initial axial positions.     

A series of tripodal cysteine derivatives as water-soluble chelators that are highly selective for copper(I)

A series of tripodal ligands derived from nitrilotriacetic acid and extended by three converging, metal-binding, cysteine chains was synthesised. Their ability to bind soft metal ions thanks to their three thiolate functions was investigated by means of complementary analytical and spectroscopic methods. Three ligands that differ by the nature of the carbonyl group next to the coordinating thiolate functions were studied: L(1) (ester), L(2) (amide) and L(3) (carboxylate). The negatively charged derivative L(3), which bears three carboxylate functions close to the metal binding site, gives polynuclear copper(I) complexes of low stability. In contrast, the ester and amide derivatives L(1) and L(2) are efficient Cu(I) chelators with very high affinities, close to that reported for the metal-sequestering metallothioneins (log K≈19). Interestingly, these two ligands form mononuclear copper complexes with a unique MS(3) coordination in water solution. An intramolecular hydrogen-bond network involving the amide functions in the upper cavity of the tripodal ligands stabilises these mononuclear complexes and was evidenced by the very low chemical-shift temperature coefficient of the secondary amide protons. Moreover, L(1) and L(2) display large selectivities for the targeted metal ion that is, Cu(I), with respect to bioavailable Zn(II). Therefore the two sulfur-based tripods L(1) and L(2) are of potential interest for intracellular copper detoxication in vivo, without altering the homeostasis of the essential metal ion Zn(II).