Triethylenetetramine penta- and hexa-acetamide ligands and their ytterbium complexes as paraCEST contrast agents for MRI

The ligand triethylenetetramine-N,N,N',N',N',N'-hexaacetamide (ttham) was synthesized with the aim of forming lanthanide complexes suitable as contrast agents for magnetic resonance imaging applications utilizing the chemical exchange-dependent saturation transfer (CEST) effect. It was designed to exclude water molecules from the first coordination sphere and provide a high number of CEST active amide protons per lanthanide ion. The ligand was characterized by its protonation behavior and its complexation properties with ytterbium ions in aqueous solution. The basicity of the ttham backbone amine protons decreases in the order N(central(1)) > N(terminal(1)) > N(terminal(2)) > N(central(2)), as deduced from NMR titration experiments and from a comparison of its protonation constants with those of two ttham derivatives, in which either a terminal (N-benzyl-triethylenetetramine-N,N',N',N',N'-pentaacetamide, 1bttpam) or a central acetamide group (N'-benzyl-triethylenetetramine-N,N,N',N',N'-pentaacetamide, 4bttpam) is substituted with a benzyl group. This protonation sequence results from the combined influence of inductive effects, the intramolecular hydrogen bonding network, and the Coulomb repulsion between protonated ammonium groups. The ytterbium complex of ttham, [Yb(ttham)]Cl(3), is coordinatively frustrated. Due to steric constraints, in addition to the four backbone nitrogen atoms, only three of the four symmetry-equivalent terminal acetamide donors can coordinate simultaneously to the ytterbium ion, and the dangling fourth one exchanges quickly with the other three. The ytterbium complexes of a total of five ligands (ttham, 1bttpam, 4bttpam, 2,2',2'-triaminotriethylaminehexaacetamide (ttaham), and diethylenetriamine-N,N,N',N',N'-pentaacetamide (dtpam)) were studied with respect to their CEST properties. In solution, all of these complexes have a low symmetry. The presence of multiple magnetically different amide groups in each complex prevents the realization of very high CEST effects. These results nevertheless form an excellent basis for a further optimization of this class of ligands.     

Experimental Technique to Characterize the Plastic Behaviour of Metallic Materials in a Wide Range of Temperatures and Strain Rates: Application to a High-Carbon Steel

This paper presents high temperature quasi-static and dynamic tensile testing. Samples are heated by an induction system controlled with a pyrometer. A high-speed camera (500 fps) is used to determine displacement fields with a digital image correlation software. For such tests a specific marking procedure of the sample is applied. This method is used to characterize the mechanical behaviour of a C68 high-carbon steel at temperatures up to 720 °C. Stress-strain curves are given from room temperature up to 720 °C at strain rates ranging from 400 /s to 4 × 10² /s.     

The holographic bubble chamber experiment and the determination of the effective charmed quark mass and theK-factor for hadronic charm production

In the first holographic bubble chamber experiment — the HOBC experiment — we have accumulated a total of 40000 holograms with particle interactions. We have determined the total charm pair cross section inpN collisions to be 23.3 _?7.7 ⁺¹⁰ μb and 3.6 _?1.7 ^+2.3 μb for 360 and 200 GeV/c incident protons respectively. We have assumed a linear dependence of the cross section on the atomic number of the target. This experiment has demonstrated the feasibility of holographic recording in small bubble chambers. Assuming that the charm cross section can be described by the standard QCD factorized expression with gluon fusion and quark-antiquark annihilation, we have used our measured charm cross sections with other measurements to determine the effective charmed quark mass to be 1.8 _?0.35 ^+0.25 GeV/c². TheK factor, which describes the importance of the higher order corrections, is calculated to be 9.8 _?6.9 ^+12.5 (See noted added in proof.)     

Ultrafast deactivation of an excited cytosine-guanine base pair in DNA

Multiconfigurational ab initio calculations and QM/MM molecular dynamics simulations of a photoexcited cytosine-guanine base pair in both gas phase and embedded in the DNA provide detailed structural and dynamical insights into the ultrafast radiationless deactivation mechanism. Photon absorption promotes transfer of a proton from the guanine to the cytosine. This proton transfer is followed by an efficient radiationless decay of the excited state via an extended conical intersection seam. The optimization of the conical intersection revealed that it has an unusual topology, in that there is only one degeneracy-lifting coordinate. This is the central mechanistic feature for the decay both in vacuo and in the DNA. Radiationless decay occurs along an extended hyperline nearly parallel to the proton-transfer coordinate, indicating the proton transfer itself is not directly responsible for the deactivation. The seam is displaced from the minimum energy proton-transfer path along a skeletal deformation of the bases. Decay can thus occur anywhere along the single proton-transfer coordinate, accounting for the remarkably short excited-state lifetime of the Watson-Crick base pair. In vacuo, decay occurs after a complete proton transfer, whereas in DNA, decay can also occur much earlier. The origin of this effect lies in the temporal electrostatic stabilization of dipole in the charge-transfer state in DNA.     

Optically active cyclopentadienyl and indenyl ligands obtained from lactic acid esters

Asymmetric cyclopentadienes and indenes are easily prepared by nucleophilic attack of LiCp or LiInd on tosylate or triflate of ethyl (S)-(−) lactate. The selectivity of the reaction depends on the nature of the leaving group. This is particularly true in the case of the reaction of LiCp with sulfonates of ethyl (S)-(−) lactate. Indeed, only the monosubstituted cyclopentadiene lactate 2 is obtained from the triflate 6, whereas from the tosylate 1, besides 2 (20%) a 1,3-disubstituted cyclopentadiene lactate 3 is isolated (16.5%). From cyclopentadiene and indene lactate 2 and 7, optically active β-hydroxycyclopentadiene 10 and β-hydroxyindene 11 are obtained by reduction with LiAlH₄. Two rhodium(I) complexes 14 and 15 have been synthesized from (R,S)-2-(cyclopentadienyl)N,N-dimethylpropanamide 12 and (S)-2-(cyclopentadiene)propan-1-ol 10, respectively. The molecular structure of these complexes has been determined. Analytical and preparative chiral HPLC have been used to determine the optical purity of the ligands and to isolate enantiopure cyclopentadienyl complexes from racemic or enantiomerically enriched rhodium(I) complexes.     

Quantification of glucuronidated and sulfated steroids in human urine by ultra-high pressure liquid chromatography quadrupole time-of-flight mass spectrometry

The urinary steroid profile is constituted by anabolic androgenic steroids, including testosterone and its relatives, that are extensively metabolized into phase II sulfated or glucuronidated steroids. The use of liquid chromatography coupled to mass spectrometry (LC-MS) is an issue for the direct analysis of conjugated steroids, which can be used as urinary markers of exogenous steroid administration in doping analysis, without hydrolysis of the conjugated moiety. In this study, a sensitive and selective ultra high-pressure liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) method was developed to quantify major urinary metabolites simultaneously after testosterone intake. The sample preparation of the urine (1 mL) was performed by solid-phase extraction on Oasis HLB sorbent using a 96-well plate format. The conjugated steroids were analyzed by UHPLC-QTOF-MS^E with a single-gradient elution of 36 min (including re-equilibration time) in the negative electrospray ionization mode. MS^E analysis involved parallel alternating acquisitions of both low- and high-collision energy functions. The method was validated and applied to samples collected from a clinical study performed with a group of healthy human volunteers who had taken testosterone, which were compared with samples from a placebo group. Quantitative results were also compared to GC-MS and LC-MS/MS measurements, and the correlations between data were found appropriate. The acquisition of full mass spectra over the entire mass range with QTOF mass analyzers gives promise of the opportunity to extend the steroid profile to a higher number of conjugated steroids.     

Clay and DOPA containing polyelectrolyte multilayer film for imparting anticorrosion properties to galvanized steel

A facile and green approach is developed to impart remarkable protection against corrosion to galvanized steel. A protecting multilayer film is formed by alternating the deposition of a polycation bearing catechol groups, used as corrosion inhibitors, with clay that induces barrier properties. This coating does not affect the esthetical aspect of the surface and does not release any toxic molecules in the environment.     

Direct variable selection for discrimination among several groups

We propose a criterion for variable selection in discriminant analysis. This criterion permits to arrange the variables in decreasing order of adequacy for discrimination, so that the variable selection problem reduces to that of the estimation of suitable permutation and dimensionality. Then, estimators for these parameters are proposed and the resulting method for selecting variables is shown to be consistent. In a simulation study, we compute proportions of correct classification after variable selection in order to gain understanding of the performance of our proposal and to compare it to existing methods.