Convenient grafting through approach for the preparation of stealth polymeric blood pool magnetic resonance imaging contrast agents

New hydrosoluble magnetic resonance imaging (MRI) macrocontrast agents are synthesized by reversible addition fragmentation chain transfer (RAFT) copolymerization of poly(ethylene oxide) methyl ether acrylate (PEOMA) with an acrylamide bearing a ligand for gadolinium, followed by the complexation of Gd³⁺. This convenient and simple grafting through approach leads to macrocontrast agents with a high relaxivity at high frequency that is imparted by the restricted tumbling of the Gd³⁺ complex caused by its attachment to the polymer backbone. Importantly a very low protein adsorption is also evidenced by the hemolytic CH50 test. It is the result of the poly(ethylene oxide) (PEO) brush that efficiently hides the gadolinium complex and renders it stealth to the proteins of the immune system. Improved contrast and long blood circulating properties are thus expected for these macrocontrast agents. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Enolizable Carbonyls and N,O‐Acetals: A Rational Approach for Room‐Temperature Lewis Superacid‐Catalyzed Direct α‐Amidoalkylation of Ketones and Aldehydes

An efficient catalytic room‐temperature direct α‐amidoalkylation of carbonyl donors, that is, ketones and aldehydes with unbiased N,O‐acetals, is described. Sn(NTf₂)₄ is an optimal catalyst to promote this challenging transformation at low loading and the reaction shows promising scope. A comprehensive and rational evaluation of this reaction has led to the establishment of an empirical scale of nucleophilic reactivity for a broad set of ketones that should be helpful in the synthetic design and development of carbonyl α‐functionalization methods.     

Electronic effects of aryl-substituted bis(oxazoline) ligands on the outcome of asymmetric copper-catalysed C–H insertion and aromatic addition reactions

The effect of the modification of bis(oxazoline) ligands on the outcome of copper-catalysed C–H insertion and aromatic addition reactions is described. In general, these reactions display minimum sensitivity in terms of enantiocontrol to variation of the electronic properties of the aryl moiety of the ligand however, some influence is observed for C–H insertions employing naphthyl-substituted bis(oxazolines) and for aromatic addition reactions of biphenyl diazo ketone substrates. The synthesis of the modified bis(oxazolines), which include four novel structures, is also described.     

Magnesium Catalysis for the Hydroboration of Carbodiimides

A β‐diketiminato magnesium alkyl complex, [CH{C(Me)NDipp}₂}MgnBu] (Dipp=2,6‐iPr₂C₆H₃), was shown to be an effective pre‐catalyst for the first reported catalytic hydroboration of alkyl‐ and aryl‐substituted carbodiimides with pinacol borane (HBpin). The catalytic reactions proceed under mild conditions to afford the corresponding N‐borylated formamidine compounds in good yields. The reactions were observed to proceed through the intermediacy of magnesium amidinate and formamidinatoborate intermediates and an example of one of these latter species has been structurally characterised by an X‐ray diffraction analysis. Crucially, no formation of the N‐boryl formamidine products was observed in the absence of additional equivalents of the carbodiimide and HBpin substrates. This observation, supported by the evolution of a sigmoidal kinetic profile for the hydroboration of dicyclohexylcarbodiimide, has been rationalised as the consequence of an allosteric effect of the pinacol borane and carbodiimide on the magnesium formamidinatoborate intermediates.     

Engineering the Big Chill: The Story of JLab’s Central Helium Liquefier

This article tells the story of the Central Helium Liquefier (CHL) at the Thomas Jefferson National Accelerator Facility (JLab), one of the US National Laboratories. JLab’s successful superconducting radio frequency accelerator was only possible because a group of JLab engineers successfully tackled a complex of difficulties to build a cryogenic system that included the CHL, a task that required advancing the frontier of cryogenic technology. Ultimately, these cryogenic advances were applied far beyond JLab to the benefit of cutting-edge programs at other US national laboratories (Oak Ridge, Brookhaven, and the Facility for Rare Isotope Beams at MSU) as well as NASA. This innovation story dramatizes the sort of engineer-driven technological problem solving that allows the successful launch and operation of experimental projects. Along the way, the CHL story also provides an important addition to our understanding of the role played by engineers and industry in creating knowledge at physics laboratories.     

Convenient Access to Fluorescent Probes by Chemoselective Acylation of Hydrazinopeptides: Application to the Synthesis of the First Far‐Red Ligand for Apelin Receptor Imaging

Herein, we develop a convenient method to facilitate the solution‐phase fluorescent labelling of peptides based on the chemoselective acylation of α‐hydrazinopeptides. This approach combines the advantages of using commercially available amine‐reactive dyes and very mild conditions, which are fully compatible with the chemical sensitivity of the dyes. The usefulness of this approach was demonstrated by the labelling of apelin‐13 peptide. Various fluorescent probes were readily synthesized, enabling the rapid optimization of their affinities for the apelin receptor. Thus, the first far‐red fluorescent ligand with sub‐nanomolar affinity for the apelin receptor was characterized and shown to track the receptor efficiently in living cells by fluorescence confocal microscopy.