Functionalized europium nanorods for in vitro imaging

Emissive europium hydroxide nanorods (ENR) (20 nm x 500 nm) functionalized by a surface coating of chromophore-containing organically modified silicate (ORMOSIL) layer, have been synthesized and characterized by high-resolution transmission electron microscopy (TEM). Low-temperature photophysical characterization of the functionalized nanorods (FENR) demonstrated a strong red 5D0 luminescence both in solid and in suspended solutions. Potentials of this nanorod material for live cell imaging have also been explored. Both the bare and functionalized nanorods are able to enter living human cells with no discernible cytotoxicity. Chromophore-to-Eu3+ energy-transfer in the functionalized nanorods enables staining of the cytoplasm of living human cells. This is confirmed by costaining with fluorescent dextran. The red chromophore-sensitized luminescence from the internalized nanorods in live human lung carcinoma cells (A549) can be observed by confocal microscopy 2 h after loading and reaches maximal emission after 24 h.     

Highly chemoselective reductive amination of carbonyl compounds promoted by InCl3/Et3SiH/MeOH system

A new strategy has been developed for reductive amination of aldehydes and ketones with the InCl3/Et3SiH/MeOH system, which is a nontoxic system with highly chemoselective and nonwater sensitive properties. The methodology can be applied to a variety of cyclic, acyclic, aromatic, and aliphatic amines. Functionalities including ester, hydroxyl, carboxylic acid, and olefin are found to be stable under our conditions. The reaction shows a first-order kinetics profile with respect to both InCl3 and Et3SiH. Spectroscopic techniques such as NMR and ESI-MS have been employed to probe the active and resulting species arising from InCl3 and Et3SiH in MeOH, which are important in deriving a mechanistic proposal. In the ESI-MS studies, we have first discovered the existence of stable methanol-coordinated indium(III) species which are presumably responsible for the gentle generation of indium hydride at room temperature. The solvent attribution was crucial in tuning the reactivity of [In-H] species, leading to the establishment of mild reaction conditions. The system is superior in flexible tuning of hydride reactivity, resulting in the system being highly chemoselective.     

Effects of Active‐Site Modification and Quaternary Structure on the Regioselectivity of Catechol‐O‐Methyltransferase

Catechol‐O‐methyltransferase (COMT), an important therapeutic target in the treatment of Parkinson's disease, is also being developed for biocatalytic processes, including vanillin production, although lack of regioselectivity has precluded its more widespread application. By using structural and mechanistic information, regiocomplementary COMT variants were engineered that deliver either meta‐ or para‐methylated catechols. X‐ray crystallography further revealed how the active‐site residues and quaternary structure govern regioselectivity. Finally, analogues of AdoMet are accepted by the regiocomplementary COMT mutants and can be used to prepare alkylated catechols, including ethyl vanillin.     

Switching liquid morphologies on linear grooves

The morphology of liquids confined to linear micrometer-sized grooves of triangular and rectangular cross section is studied for different substrate wettabilities. Depending on the wettability and exact geometry, either droplike morphologies or elongated liquid filaments represent the generic equilibrium structures on the substrate. Upon changing the apparent contact angle of aqueous drops by electrowetting, we are able to trigger the transition between elongated filaments and droplets. In the case of rectangular grooves, this transition allows us to advance liquid reversibly into the grooves while crossing a certain threshold contact angle. In triangular grooves, however, these elongated filaments undergo a dynamic instability when the contact angle returns to a value above the filling threshold. The different filling and drainage behavior is explained by specific aspects of the triangular and rectangular groove geometry.     

Structural characterization of shielded isomeric europium complexes with metal-metal contact

New luminescent isomeric europium(III) complexes with carboxylic carbonyl group coordination (I and II) have been prepared by solvothermal synthesis using the ligand 2,2'-bipyridine-4,4'-dicarboxylic acid (bpdc), with the nonradiatively shielded Eu3+ coordination sphere completed by dimethyl sulfoxide ligands. The room temperature IR spectra and Eu3+ luminescence spectra do not provide a definitive distinction between I and II, but low-temperature luminescence can give a clear identification.     

Perfusion MR imaging and proton MR spectroscopic imaging in differentiating necrotizing cerebritis from glioblastoma multiforme

We describe a lesion with the magnetic resonance imaging (MRI) characteristics of a glioblastoma mutiforme and demonstrate how perfusion MRI and proton MR spectroscopic imaging can be used to differentiate necrotizing cerebritis from what appeared to be a high-grade glioma. A 43-year-old woman presented to her physician complaining of progressive visual disturbance and headache for several weeks. Conventional MRI demonstrated a parietal peripherally enhancing mass with central necrosis and moderate to severe surrounding T2 hyperintensity, suggesting an infiltrating high-grade glioma. However, advanced imaging, including dynamic susceptibility contrast MRI (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI), suggested a nonneoplastic lesion. The DSC MRI data demonstrated no hyperperfusion within the lesion and surrounding T2 signal abnormality, and the MRSI data showed overall decrease in metabolites in this region, except for lactate. Because of the aggressive appearance to the lesion and the patients' worsening symptoms, a biopsy was performed. The pathologic diagnosis was necrotizing cerebritis. After the commencement of steroid therapy, imaging findings and patient symptoms improved. This report will review the utility of advanced imaging for differentiating inflammatory from neoplastic appearing lesions on conventional imaging.     

Profiting from nature: macroporous copper with superior mechanical properties

Macroporous copper with a complex hyperbolic morphology and superior mechanical properties was produced by replicating the remarkable form of a sea urchin skeletal plate using templated electrochemical deposition.     

Recent advances in supramolecular self-assembly and biological applications of luminescent alkynylplatinum(II) polypyridine complexes

Among various transition metal complexes, platinum(II) complexes are among one of the most extensively explored classes of metal complexes for supramolecular assembly, as their square-planar molecular geometry allows axial interactions between adjacent complex molecules and access to the formation of supramolecular assemblies with the aid of noncovalent Pt(II)⋯Pt(II) interactions. In the presence of external stimuli, alkynylplatinum(II) polypyridine complexes can self-assemble with alterations in their spectroscopic and luminescence properties. In light of their inherent advantages, including low-energy photoexcitation, red to near-infrared emission, large Stokes shifts, long phosphorescence lifetimes and high photostability, successful applications of alkynylplatinum(II) polypyridine complexes in the detection of biological analytes have been made possible. In this account, presented in part of the FACS Foundation Lecture, we introduce the basic concepts and our recent advances in the development of detection assays for various biomolecules based on luminescent alkynylplatinum(II) polypyridine complexes with selected examples.     

Application and Structural Analysis of Triazole-Bridged Disulfide Mimetics in Cyclic Peptides

Ruthenium-catalysed azide–alkyne cycloaddition (RuAAC) provides access to 1,5-disubstituted 1,2,3-triazole motifs in peptide engineering applications. However, investigation of this motif as a disulfide mimetic in cyclic peptides has been limited, and the structural consequences remain to be studied. We report synthetic strategies to install various triazole linkages into cyclic peptides through backbone cyclisation and RuAAC cross-linking reactions. These linkages were evaluated in four serine protease inhibitors based on sunflower trypsin inhibitor-1. NMR and X-ray crystallography revealed exceptional consensus of bridging distance and backbone conformations (RMSD<0.5 Å) of the triazole linkages compared to the parent disulfide molecules. The triazole-bridged peptides also displayed superior half-lives in liver S9 stability assays compared to disulfide-bridged peptides. This work establishes a foundation for the application of 1,5-disubstituted 1,2,3-triazoles as disulfide mimetics.