A Universal Cassette-Based System for the Dissolution of Solid Targets

Cyclotron-based radionuclides production by using solid targets has become important in the last years due to the growing demand of radiometals, e.g., ⁶⁸Ga, ⁸⁹Zr, ^43/47Sc, and ^52/54Mn. This shifted the focus on solid target management, where the first fundamental step of the radiochemical processing is the target dissolution. Currently, this step is generally performed with commercial or home-made modules separated from the following purification/radiolabelling modules. The aim of this work is the realization of a flexible solid target dissolution system to be easily installed on commercial cassette-based synthesis modules. This would offer a complete target processing and radiopharmaceutical synthesis performable in a single module continuously. The presented solid target dissolution system concept relies on an open-bottomed vial positioned upon a target coin. In particular, the idea is to use the movement mechanism of a syringe pump to position the vial up and down on the target, and to exploit the heater/cooler reactor of the module as a target holder. All the steps can be remotely controlled and are incorporated in the cassette manifold together with the purification and radiolabelling steps. The performance of the device was tested by processing three different irradiated targets under different dissolution conditions.     

Information theoretical study of chirality: enantiomers with one and two asymmetric centra

In this work, the Kullback-Leibler information deficiency is probed as a chirality measure. It is argued that the information deficiency, calculated using the shape functions of the R and S enantiomers, considering one as reference for the other, gives an information theory based expression useful for quantifying chirality. The measure is evaluated for five chiral halomethanes possessing one asymmetric carbon atom with hydrogen, fluorine, chlorine, bromine, and iodine as substituents. To demonstrate the general applicability, a study of two halogen-substituted ethanes possessing two asymmetric carbon atoms has been included as well. The basic expression of the sum of the local information deficiency over all atoms can be decomposed into separate summations over coinciding and noncoinciding atoms, or into a global and a mixing entropy term, or into a local entropy contribution for each atom individually based on the Hirshfeld partitioning. Avnir's continuous chirality measure (CCM) has been computed and confronted with the information deficiency. Finally, the relationship between chirality and optical rotation is used to study the proposed measure. The results illustrate Mezey's holographic electron density theorem with an intuitively appealing division of the strength of propagation of the atomic chirality from an asymmetric carbon atom throughout the molecule. The local information deficiency of the carbon atom is proposed as a measure of chirality; more precisely, the difference in information between the R and the S enantiomer turns out to be a quantitative measure of the chirality of the system. It may be evaluated as the arithmetic mean of the different alignments, or considering only the alignment resulting in the highest similarity value, or using the QSSA alignment.     

Thermally stable and organosoluble binaphthylene‐based poly(urea‐ether‐imide)s: one‐pot preparation and characterization

A new family of wholly aromatic poly(urea‐ether‐imide)s ( 4a–4f ) possessing binaphthylene‐twisted rings was prepared by diphenyl azidophosphate (DPAP)‐activated one‐pot polyaddition reaction of a preformed imide heterocyclic ring‐containing dicarboxylic acid, 2,2′‐bis(4‐trimellitimidophenoxy)‐ 1,1′‐binaphthyl ( 1 ) with various kinds of aromatic diamines ( 3a–3f ). At first, with due attention to structural similarity and to compare the characterization data, a model compound 2 was synthesized by the reaction of diimide‐dicarboxylic acid 1 with two mole equivalents of aniline. In this direct method, the polymers were prepared by polyaddition reactions of the in situ‐formed diisocyanate with the aromatic diamines. Molecular weights of the poly(urea‐ether‐imide)s obtained were evaluated viscometrically, and the inherent viscosities (η_inh) measured were in the range 0.10– 0.25 dl/g. All of the polymers were characterized by FT‐IR spectroscopic method and elemental analysis. All of the resulting polymers exhibited an excellent solubility in common polar solvents such as N‐methyl‐2‐pyrrolidone (NMP), dimethyl sulfoxide (DMSO), N,N‐dimethylformamide (DMF), and N,N‐dimethylacetamide (DMAc). Crystallinity of the resulted polymers was evaluated by wide‐angle X‐ray diffraction (WXRD) method, and they exhibited nearly a non‐crystalline nature as evidenced by their diffractograms. The glass transition temperatures (T_g) of the polymers determined by differential scanning calorimetry (DSC) thermograms were in the range of 274–302°C. The temperatures at 10% weight loss (T_d10%) from their thermogravimetric analysis (TGA/DTG) curves were found to be in the range of 389–414°C in nitrogen atmosphere. Copyright © 2008 John Wiley & Sons, Ltd.     

Rapid and sensitive analysis of vincristine in human plasma using on-line extraction combined with liquid chromatography/tandem mass spectrometry

A simple and rapid method has been developed and validated for the quantitation of vincristine in human plasma by liquid chromatography/tandem mass spectrometry (LC/MS/MS) with atmospheric pressure chemical ionization using on-line solid-phase extraction. The method uses vinblastine as internal standard and the sample preparation is limited just to a plasma protein precipitation step. Further sample clean-up is carried out on-line through a perfusion column preceding an analytical phenyl LC column, the latter directly connected to the mass spectrometer. Quantitation is performed in multiple reaction monitoring mode using the transitions of m/z 825.3 --> 765.3 and 811.3 --> 751.3 for vincristine and vinblastine respectively. The assay was linear (r2 > or =0.99) in a concentration range from 0.1 to 500 ng/mL. Carry-over, measured on the experimental set-up, was less than 0.04%. Recovery for vincristine and the internal standard was within 90-95%. The intra-day and inter-day assay precision ranged from 1.2% to 6.8% RSD while mean percentage deviation from nominal value ranged from 0.01% to 6.1%. The proposed assay was found suitable for pharmacokinetics investigations and clinical therapeutic drug monitoring especially in pediatric cancer patients.     

Cholesterylbutyrate solid lipid nanoparticles as a butyric acid prodrug

Cholesterylbutyrate (Chol-but) was chosen as a prodrug of butyric acid. Butyrate is not often used in vivo because its half-life is very short and therefore too large amounts of the drug would be necessary for its efficacy. In the last few years butyric acid's anti-inflammatory properties and its inhibitory activity towards histone deacetylases have been widely studied, mainly in vitro. Solid Lipid Nanoparticles (SLNs), whose lipid matrix is Chol-but, were prepared to evaluate the delivery system of Chol-but as a prodrug and to test its efficacy in vitro and in vivo. Chol-but SLNs were prepared using the microemulsion method; their average diameter is on the order of 100-150 nm and their shape is spherical. The antineoplastic effects of Chol-but SLNs were assessed in vitro on different cancer cell lines and in vivo on a rat intracerebral glioma model. The anti-inflammatory activity was evaluated on adhesion of polymorphonuclear cells to vascular endothelial cells. In the review we will present data on Chol-but SLNs in vitro and in vivo experiments, discussing the possible utilisation of nanoparticles for the delivery of prodrugs for neoplastic and chronic inflammatory diseases.     

Crystal structure and DFT calculations of Cp2NbH(SiIMe2)(SiFMe2): an asymmetric bis(silyl) niobocene hydride complex

An asymmetric bis(silyl) niobocene hydride complex, namely, bis(η⁵-cyclopentadienyl)(fluorodimethylsilyl)hydrido(iododimethylsilyl)niobium, [Nb(C₅H₅)₂(C₂H₆FSi)(C₂H₆ISi)H] or Cp₂NbH(SiIMe₂)(SiFMe₂), has been studied to determine the effect of the silyl ligand on the position of the hydride attached to the Nb atom. It has been shown that when a Group 17 atom is substituted onto one of the silyl ligands, there is a greater interaction between the hydride and this ligand, as demonstrated by a shorter Si…H distance. In the present work, we have investigated the effect when the silyl ligands are substituted by different Group 17 atoms. We present here the structure and DFT calculations of Cp₂NbH(SiIMe₂)(SiFMe₂), showing that the position of the hydride is located between the two silyl ligands. The results from our investigation show that the hydride is closer to the silyl ligand that is substituted by fluorine.     

Influence of crosslinker identity and position on gas-phase dissociation of lys-lys crosslinked peptides

A systematic study of the dissociation patterns of crosslinked peptides analyzed by tandem mass spectrometry is reported. A series of 11-mer peptides was designed around either a polyalanine or polyglycine scaffold with arginine at the C terminus. One or two lysine residues were included at various locations within the peptides to effect inter- or intra-molecular crosslinking, respectively. Crosslinked species were generated with four commonly used amine-specific chemical crosslinking reagents: disuccinimidyl suberate (DSS), disuccinimidyl tartarate (DST), dithiobis(succinimidylpropionate) (DSP), and disuccinimidyl glutarate (DSG). The influence of precursor charge state, location of crosslink, and specific crosslinking reagent on the MS/MS dissociation pattern was examined. Observed trends in the dissociation patterns obtained for these species will allow for improvements to software used in the automated interpretation of crosslinked peptide MS/MS data.     

Multiorbital interactions during Acyl radical addition reactions involving imines and electron-rich olefins

Ab initio and DFT calculations reveal that acyl radicals add to imines and electron-rich olefins through simultaneous SOMO --> pi*, pi --> SOMO, and HOMO --> pi*C=O interactions between the radical and the radicalophile. At the CCSD(T)/aug-cc-pVDZ//QCISD/cc-pVDZ level, energy barriers of 15.6 and 17.9 kJ mol(-1) are calculated for the attack of the acetyl radical at the carbon and nitrogen ends of methanimine, respectively. These barriers are 17.1 and 20.4 kJ mol(-1) at BHandHLYP/cc-pVDZ. In comparison, barriers of 34.0 and 23.4 kJ mol(-1) are calculated at BHandHLYP/cc-pVDZ for reaction of the acetyl radical at the 1- and 2-positions in aminoethylene, repectively. Natural bond orbital (NBO) analysis at the BHandHLYP/6-311G** level of theory reveals that SOMO --> pi*imine, pi imine--> SOMO, and LPN --> pi*C=O interactions are worth 90, 278, and 138 kJ mol-1, respectively, in the transition state (2) for reaction of acetyl radical at the nitrogen end of methanimine; similar interactions are observed for the chemistry involving aminoethylene. These multiorbital interactions are responsible for the unusual motion vectors associated with the transition states involved in these reactions. NBO analyses for the remaining systems in this study support the hypothesis that the acetyl radical is ambiphilic in nature.     

Structural and spectroscopic characterization of copper(II) complexes of a new bisamide functionalized imidazole tripod and evidence for the formation of a mononuclear end-on Cu-OOH species

A new polyimidazole tripod N,N-bis((1-methyl-4-pivalamidoimidazol-2-yl)methyl)-N'-((1-methylimidazol-2-yl)methyl)amine (L2) has been synthesized and shown to form intramolecular hydrogen bonds with different axial ligands bonded to Cu(II) in the solid state. The same hydrogen-bonding property of L2 appears responsible for the stabilization of a Cu(II)-OOH species in solution. The crystal structures of L2 and three of its Cu(II) complexes are reported. The [Cu(L2)X]ClO4 complexes, 4-6 (X- = Cl-, OH-, or N3-) have distorted trigonal bipyramidal geometries in the solid state and have been characterized further by UV-vis absorption, electron paramagnetic resonance (EPR) spectroscopy, and cyclic voltammetry. The reaction of [Cu(L2)OH](ClO4) (5) with H2O2 and tert-butyl hydroperoxide in methanol generates [Cu(L2)OOH](ClO4) (7) and [Cu(L2)OO(t)Bu](ClO4) (8) which have been characterized by different spectroscopic methods. The compound [Cu(L2)OO(t)Bu]+ displays a band at 395 nm (epsilon = 950 M(-1) cm(-1)) assigned to an alkylperoxo pi*(sigma) --> Cu ligand-to-metal charge transfer (LMCT) transition, while [Cu(L2)OOH]+ displays a peroxo pi*(sigma) --> Cu charge-transfer transition at 365 nm with epsilon = 1300 M(-1) cm(-1), a mass ion at m/z 593.4, and nu(O-O) stretch (resonance Raman) at 854 cm(-1) that shifts to lower energy by 46 cm(-1) upon 18O substitution.