Synthesis and characterization of an MRI Gd‐based probe designed to target the translocator protein

DPA‐713 is the lead compound of a recently reported pyrazolo[1,5‐a]pyrimidineacetamide series, targeting the translocator protein (TSPO 18 kDa), and as such, this structure, as well as closely related derivatives, have been already successfully used as positron emission tomography radioligands. On the basis of the pharmacological core of this ligands series, a new magnetic resonance imaging probe, coded DPA‐C₆‐(Gd)DOTAMA was designed and successfully synthesized in six steps and 13% overall yield from DPA‐713. The Gd‐DOTA monoamide cage (DOTA = 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) represents the magnetic resonance imaging reporter, which is spaced from the phenylpyrazolo[1,5‐a]pyrimidineacetamide moiety (DPA‐713 motif) by a six carbon‐atom chain. DPA‐C₆‐(Gd)DOTAMA relaxometric characterization showed the typical behavior of a small‐sized molecule (relaxivity value: 6.02 mM^?1 s^?1 at 20 MHz). The good hydrophilicity of the metal chelate makes DPA‐C₆‐(Gd)DOTAMA soluble in water, affecting thus its biodistribution with respect to the parent lipophilic DPA‐713 molecule. For this reason, it was deemed of interest to load the probe to a large carrier in order to increase its residence lifetime in blood. Whereas DPA‐C₆‐(Gd)DOTAMA binds to serum albumin with a low affinity constant, it can be entrapped into liposomes (both in the membrane and in the inner aqueous cavity). The stability of the supramolecular adduct formed by the Gd‐complex and liposomes was assessed by a competition test with albumin. Copyright © 2013 John Wiley & Sons, Ltd.     

Complete assignment of the 1H and 13C NMR spectra of antimicrobial 4‐arylamino‐ 3‐nitrocoumarin derivatives

Herein, we describe the synthesis and complete assignment of the ¹H and ¹³C NMR chemical shifts of a series of antimicrobial 4‐arylamino‐3‐nitrocoumarin derivatives based on a combination of ¹H and ¹³C NMR, ¹H‐¹H‐COSY, NOESY, HSQC and HMBC experiments. Conformational effects upon the chemical shifts of the coumarin moiety arising from the anisotropy of the aryl side group are briefly discussed. This study provides the first complete and fully assigned NMR data for this important group of antimicrobial compounds and bridges the gap existing in the literature with regard to NMR structural data for 4‐arylamino‐3‐nitrocoumarins. Copyright © 2010 John Wiley & Sons, Ltd.     

High Sensitive Microsensor Based on Organic‐Inorganic Composite for Two‐Dimensional Mapping of H2O2 by SECM

The present work describes the development of a selective, sensitive and stable sensing microsensor for scanning electrochemical microscopy (SECM) to measure H₂O₂ during electrochemical reduction of oxygen. The microsensor is based on graphene and Poly(3,4‐ethylenedioxythiophene) composite as support to iron (III) hexacyanoferrate (II) (PEDOT/graphene/Fe^III₄[Fe^II(CN)₆]₃ microsensor). The electrochemical properties of the PEDOT/graphene/Fe^III₄[Fe^II(CN)₆]₃ microsensor were investigated by cyclic voltammetry (CV) and scanning electrochemical microscopy (SECM). The PEDOT/graphene/Fe^III₄[Fe^II(CN)₆]₃ microsensor showed an excellent electrocatalytic activity toward hydrogen peroxide (H₂O₂) reduction with a diminution of the overpotential of about 500 mV in comparison to the process at a bare gold microelectrode. The microsensor presented excellent performance for two dimensional mapping of H₂O₂ by SECM in 0.1 mol L^?1 phosphate buffer solution (pH 7.0). Under optimized conditions, a linear response range from 1 up to 1000 µmol L^?1 was obtained with a sensitivity of 0.08 nA L µmol^?1 and limit of detection of 0.5 µmol L^?1.     

Eco-friendly process toward collector- and binder-free,high-energy density electrodes for lithium-ion batteries

Journal of Solid State Electrochemistry - The preparation of collector- and binder-free, high-energy density cathodes made from carbon-coated LiFePO4 (C-LFP) and single-walled carbon nanotubes...     

Variance of the virtual displacement

We show that the affine structure of the 3-dimensional space is deeply enmeshed with the static laws expression. The relevance of tensorial rules for calculus in mechanics is thus enhanced. The virtual work principle is stated precisely but a little twist is given to the usual statements: the tensorial nature of the so-called virtual displacement vector is asserted to be covariant. To cite this article: C. Vallée et al., C. R. Mecanique 332 (2004).

Résumé

Nous montrons que la structure affine de l'espace tridimensionnel est fortement imbriquée avec l'expression des lois de la statique. La pertinence de l'application des règles du calcul tensoriel à la mécanique est ainsi renforcée. Le principe des travaux virtuels est établi précisément avec une seule entorse aux exposés classiques : la nature tensorielle de l'habituel vecteur déplacement virtuel est affirmée covariante. Pour citer cet article : C. Vallée et al., C. R. Mecanique 332 (2004).     

13CH4分子v3振动带空气和氮气加宽系数温度依赖性研究

采用中红外波段连续可调谐二极管激光器和自行研制的低温吸收池, 测量了温度为296 K, 252 K, 213 K, 173 K时, 3.38 μm附近¹³CH₄分子的四条跃迁谱线的氮气和空气加宽光谱; 首次通过实验获得空气和氮气对¹³CH₄分子的碰撞加宽系数, 以及谱线加宽系数的温度依赖系数. 实验过程中, 利用Voigt线型对所测量的光谱进行拟合. 实验结果表明, 氮气和空气对¹³CH₄分子的碰撞诱导加宽系数随温度的降低而增大; 相同温度下, 氮气对¹³CH₄分子的碰撞加宽系数普遍大于空气加宽系数. 实验数据为地球和外星体大气遥感探测提供了依据.     

Hindered coarsening of a phase-separating microemulsion due to dispersed colloidal particles

The addition of sterically stabilized colloidal particles to a phase-separating microemulsion leads to dramatic changes in its demixing behavior, especially during the later stages. Our microemulsion is composed of reverse micelles of sodium dodecyl sulfate, pentanol, and water in a dodecane continuous phase which separates into micelle-rich and micelle-poor phases above a lower critical solution temperature. The poly(methyl methacrylate) particles preferentially partition into the less structured, micelle-poor phase. Nucleation of the minority phase or spinodal decomposition close to criticality continue to occur in the presence of particles, albeit with pronounced pretransitional clustering of particles when the micelle-poor phase is in the minority. The coalescence of micelle-poor droplets and the coarsening of micelle-rich domains are both strongly modified due to the presence of colloidal particles. We use our observations of the early stages of phase separation to understand these late stage changes.     

ToF-SIMS imaging and depth profiling of HeLa cells treated with bromodeoxyuridine

Time of flight secondary ion mass spectrometry 2D images and molecular depth profiles of human HeLa cells treated with bromodeoxyuridine (BrdU) were acquired in the dual beam mode (Bi(3) (+) analysis beam, C(60) (+) etching beam). Several preparation protocols were investigated and were compared to a simple wash-and-dry method. The feasibility of using C(60) to clean the samples prior to imaging with Bi was also investigated quantitatively by calibrating full depth profiles of the cells using atomic force microscopy. BrdU was used as a marker for the cell nucleus, facilitating identification and localization of sub-cellular features during depth profiling. Results show that C(60) can be used to remove the surface contamination and to access different layers within the cells for 2D imaging. For a 1 nA, 10 keV C(60) (+) beam incident at 45° and rastered over a 500 × 500 μm(2) area, ~1 nm of biological material was sputtered every second. Our results show that HeLa cells were completely removed after etching with 1.3×10(15) C(60) (+) ions per cm(2), giving an average etching rate of 3.9 nm for every 10(13) C(60) per cm(2) at 10 keV and 45° incidence.     

Antisense and antigene inhibition of gene expression by cell-permeable oligonucleotide-oligospermine conjugates

Oligonucleotides and their derivatives are a proven chemical strategy for modulating gene expression. However, their negative charge remains a challenge for delivery and target recognition inside cells. Here we show that oligonucleotide-oligospermine conjugates (Zip nucleic acids or ZNAs) can help overcome these shortcomings by serving as effective antisense and antigene agents. Conjugates containing DNA and locked nucleic acid (LNA) oligonucleotides are active, and oligospermine conjugation facilitates carrier-free cell uptake at nanomolar concentrations. Conjugates targeting the CAG triplet repeat within huntingtin (HTT) mRNA selectively inhibit expression of the mutant huntingtin protein. Conjugates targeting the promoter of the progesterone receptor (PR) function as antigene agents to block PR expression. These observations support further investigation of ZNA conjugates as gene silencing agents.