Synthesis,characterization and anticancer activity of new palladacycles derived from chiral α‐diimines

Optically pure α‐diimines quantitatively obtained in solvent‐free conditions starting from 2,3‐butanedione and (S)‐(?)‐1‐phenylethylamine and (S)‐(?)‐1‐(4‐methylphenyl)ethylamine, respectively, yielded the new chiral mono‐Pd complexes 2a–b, which have been partly characterized by IR, ¹H‐ and ¹³C‐NMR spectroscopies along with MS‐FAB⁺ spectrometry. The crystal and molecular structure for palladacycle 2a has been fully confirmed by single‐crystal X‐ray studies. Studies in vitro of 2a–b have displayed growth inhibition against different classes of cancer: leukemia (K‐562 CML), colon cancer (HCT‐15), breast cancer (MCF‐7), central nervous system (U‐251 Glio) and prostate cancer (PC‐3) cell lines. Copyright © 2009 John Wiley & Sons, Ltd.     

Metal Triflimidates: Better than Metal Triflates as Catalysts in Organic Synthesis—The Effect of a Highly Delocalized Counteranion

The continuously increasing need for novel and selective methods in organic synthesis to aid drug discovery and to address environmental concerns is a constant source of stimulation to develop novel and more efficient reaction systems. This has often resulted in a focus on transition metals, ligands, and additives, with much less attention paid to the counterion(s) of the metal cation. Recently, metal salts with one or more triflimidate counterion(s) have appeared as a unique class of catalysts that display outstanding σ‐ and π‐Lewis acid character. The highly delocalized nature of the triflimidate counterion, combined with its high steric hindrance results in virtually no nucleophilic behavior and an extremely high positive charge density on the metal cation, thus enhancing its Lewis acid character. Consequently, these metal triflimidates often outperform their metal halide or triflate analogues. This Review describes general methods for the preparation of metal triflimidate salts and their use as catalysts.     

Homoleptic Zincate‐Promoted Room‐Temperature Halogen–Metal Exchange of Bromopyridines

Homoleptic lithium tri‐ and tetraalkyl zincates were reacted with a set of bromopyridines. Efficient and chemoselective bromine–metal exchanges were realized at room temperature with a substoichiometric amount of nBu₄ZnLi₂?TMEDA reagent (1/3 equiv; TMEDA=N,N,N′,N′‐tetramethylethylenediamine). This reactivity contrasted with that of tBu₄ZnLi₂?TMEDA, which was inefficient below one equivalent. DFT calculations allowed us to rationalize the formation of N???Li stabilized polypyridyl zincates in the reaction. The one‐pot difunctionalization of dibromopyridines was also realized using the reagent stoichiometrically. The direct creation of C? Zn bonds in bromopyridines enabled us to perform efficient Negishi‐type cross‐couplings.     

CE‐ESI‐TOF/MS for human growth hormone analysis

CE is a powerful analytical tool used to separate intact biomolecules such as proteins. The coupling of CE with TOF/MS produces a very promising method that can be used to detect and identify proteins in different matrices. This paper describes an efficient, rapid, and simple CE‐ESI‐TOF/MS procedure for the analysis of endogenous human growth hormone and recombinant human growth hormone without sample preparation. Operational factors were optimized using an experimental design, and the method was successfully applied to distinguish human growth hormone and recombinant human growth hormone in unknown samples.     

Control of degradation of polypropylene during its radical functionalisation with furan and thiophene derivatives

The traditional melt radical functionalisation of isotactic polypropylene (iPP) with maleic anhydride (MAH) and peroxide affords functionalized samples with a severe decrease of the average molecular weight (MW) due to the β-scission reaction. In this work new push-pull unsaturated molecules were investigated, consisting of a heterocyclic ring conjugated with a double bond bearing an electron attracting group. These molecules were specifically designed as MAH substitute able to limit the iPP degradation, while providing functionalisation through grafting. Butyl 3-(2-furanyl) propenoate (BFA) and butyl 3-(2-thienyl) propenoate (BTA) were comparatively tested. The analysis of the reaction products indicated that both molecules are able to graft onto the iPP backbone by prompt reaction with the macro-radicals formed through H-abstraction from iPP chains, thereby significantly limiting the MW decrease, as the functionalized macro-radicals are stabilized by resonance. Nonetheless, some of iPP macro-radicals can give a parallel chain scission before reacting with the new molecules. In the case of BFA, coupling reactions of the formed macro-radicals can lead to the formation of branched high MW architectures, whereas in the case of the thiophene derivative (BTA) only a partial retaining of polymer chain fragmentation was observed due to the reduction of β-scission.     

Light-induced degradation of the active layer of polymer-based solar cells

Polymer-based organic solar cells are known to offer a poor stability in real use conditions, and the photodegradation of the active organic layer plays an important role in the reduced lifetime of the devices. This paper focuses on the photodegradation of two conjugated polymers used in organic solar cells, namely poly(2-methoxy-5-(3′,7′-dimethyloctyloxy)-1,4-phenylenevinylene (MDMO-PPV) and poly(3-hexyylthiophene) (P3HT), and their blends with [60]PCBM (methano-fullerene[6,6]-phenyl C61-butyric acid methyl ester), a fullerene derivative. MDMO-PPV and P3HT thin films were submitted to photoageing (λ > 300 nm) in the presence and in the absence of oxygen. The mechanisms by which these polymers degrade were elucidated. P3HT, pristine and blended with PCBM, was shown to be much more stable under illumination than MDMO-PPV. The results showed that, if deposited on an inert substrate and well protected from oxygen with a convenient encapsulation, P3HT:PCBM based active layer should be intrinsically stable for several years in use conditions.     

Radiolabeled small molecule protein kinase inhibitors for imaging with PET or SPECT

Imaging protein kinase expression with radiolabeled small molecule inhibitors has been actively pursued to monitor the clinical potential of targeted therapeutics and treatments as well as to determine kinase receptor density changes related to disease progression. The goal of the present review is to provide an overview of the breadth of radiolabeled small molecules that have been synthesized to target intracellular protein kinases, not only for imaging in oncology, but also for other areas of interest, particularly the central nervous system. Considerable radiotracer development has focused on imaging receptor tyrosine kinases of growth factors, protein kinases A, B and C, and glycogen synthase kinase-3?. Design considerations, structural attributes and relevant biological results are summarized.     

Screening of pesticides in blood with liquid chromatography–linear ion trap mass spectrometry

In clinical or forensic toxicology, general unknown screening procedures are used to identify as many xenobiotics as possible, belonging to numerous chemical classes. We present here a general unknown screening procedure based on liquid chromatography coupled with use of a single linear ion trap mass spectrometer, and focus on the identification of pesticides and/or metabolites in whole blood. After solid-phase extraction (SPE), the compounds of interest were separated using a reversed-phase column and identified by the mass spectrometer operated first in the full-scan mass spectrometry (MS) mode, in the positive and negative polarities, followed by MS² and MS³ scanning of ions selected in data-dependent acquisition. The total scan time was 2.45 s. Two mass spectral libraries (MS² and MS³), each of 450 spectra, were created for the 320 pesticides and metabolites detected after injection of pure solutions. Robustness of the spectra and matrix effects were studied and were satisfactory for the present application. Detection limits for the 320 compounds were studied by extracting 1 mL spiked blood at concentrations between 10 μg/L and 10 mg/L. If necessary, it was possible to decrease the detection limits of some compounds by 10–100-fold by scanning MS² in only one polarity, owing to a shorter total scan time. However, at the same time, the detection specificity decreased as no confirmation could be recorded in the following MS³ scan and no information could be registered in the other polarity. So, in these rare cases, confirmation by another method was required.     

New Gilman-type lithium cuprate from a copper(II) salt: synthesis and deprotonative cupration of aromatics

Deprotonative cupration of aromatics including heterocycles (anisole, 1,4-dimethoxybenzene, thiophene, furan, 2-fluoropyridine, 2-chloropyridine, 2-bromopyridine, and 2,4-dimethoxypyrimidine) was realized in tetrahydrofuran at room temperature using the Gilman-type amido-cuprate (TMP)₂CuLi in situ prepared from CuCl₂·TMEDA through successive addition of 1 equiv of butyllithium and 2 equiv of LiTMP. The intermediate lithium (hetero)arylcuprates were evidenced by trapping with iodine, allyl bromide, methyl iodide, and benzoyl chlorides, the latter giving the best results. Symmetrical dimers were also prepared from lithium azine and diazine cuprates using nitrobenzene as an oxidative agent.