Highly diastereoselective mannich-type reactions of chiral N-acylhydrazones

The Lewis acid-mediated addition of silyl enolates to easily accessible homochiral N-acylhydrazones derived from 3-amino-2-oxazolidinones proceeded in yields up to 71% and diastereomeric ratios of 99:1. In most cases, optimal reaction conditions entailed the simple use of ZnCl(2) in acetonitrile at room temperature. Hydrazones derived from phenyl-, isopropyl-, and benzyl-substituted 2-oxazolidinones were examined in the reaction in terms of yield and diastereoselectivity. The facile SmI(2)-mediated N-N bond cleavage of the formed hydrazines was demonstrated yielding a beta-amino acid derivative. Hence, the overall reaction sequence constitutes an efficient asymmetric Mannich-type reaction. The sense of diastereoselectivity was explained by a preferential attack on the less shielded Si face of the chiral hydrazones and confirmed by means of X-ray crystallography.     

Poly(9,9-dialkyl-3,6-dibenzosilole)--a high energy gap host for phosphorescent light emitting devices

The preparation of the 3,6-disubstituted dibenzosilole monomers , and by two different routes is described; Suzuki copolymerisation afforded poly(9,9-dioctyl-3,6-dibenzosilole) which has a sufficiently high triplet energy (2.55 eV) to function as a host for green electrophosphorescent emitters.     

Bis(mu-oxo)dicopper(III) complexes of a homologous series of simple peralkylated 1,2-diamines: steric modulation of structure, stability, and reactivity

We have synthesized and characterized bis(mu-oxo)dicopper(III) dimers 1b-4b (Os) based on a core family of peralkylated trans-(1R,2R)-cyclohexanediamine (CD) ligands, self-assembled from the corresponding [LCu(MeCN)]CF3SO3 species 1a-4a and O2 at 193 K in aprotic media; additional Os based on peralkylated ethylenediamine and tridentate polyazacyclononane ligands were synthesized analogously for comparative purposes (5b-7b and 8b-9b, respectively). Trigonal-planar [LCu(MeCN)]1+ species are proposed as the active O precursors. The 3-coordinate Cu(I) complexes [(L(TE))Cu(MeCN)]CF3SO3 (4a) and [(L(TB))Cu(MeCN)]CF3SO3 (10a) were structurally characterized; the apparent O2-inertness of 10a correlates with the steric demands of its four benzyl substituents. The rate of O formation, a multistep process that likely proceeds via associative formation of a 1:1 [LCu(O2)]1+ intermediate, exhibits significant dependence upon ligand sterics and solvent: oxygenation of 4a-the slowest-reacting O precursor of the CD series-is first-order with respect to [4a] and proceeds at least 300 times faster in tetrahydrofuran than in CH2Cl2. The EPR, UV-vis, and resonance Raman spectra of 1b-9b are all characteristic of the diamagnetic bis(mu-oxo)dicopper(III) core. The intense ligand-to-metal charge transfer absorption maxima of CD-based Os are red-shifted proportionally with increasing peripheral ligand bulk, an effect ascribed to a slight distortion of the [Cu2O2] rhomb. The well-ordered crystal structure of [(L(ME))2Cu2(mu-O)2](CF3SO3)2.4CH2Cl2 ([3b. 4CH2Cl2]) features the most metrically compact [Cu2O2]2+ core among structurally characterized Os (av Cu-O 1.802(7) A; Cu...Cu 2.744(1) A) and exemplifies the minimal square-planar ligation environment necessary for stabilization of Cu(III). The reported Os are mild oxidants with moderate reactivity toward coordinating substrates, readily oxidizing thiols, certain activated alkoxides, and electron-rich phenols in a net 2e-, 2H+ process. In the absence of substrates, 1b-9b undergo thermally induced autolysis with concomitant degradation of the polyamine ligands. Ligand product distribution and primary kinetic isotope effects (kobsH/kobsD approximately 8, 1b/d24-1b, 293 K) support a unimolecular mechanism involving rate-determining C-H bond cleavage at accessible ligand N-alkyl substituents. Decomposition half-lives span almost 3 orders of magnitude at 293 K, ranging from approximately 2 s for 4b to almost 30 min for d(24)-1b, the most thermally robust dicationic O yet reported. Dealkylation is highly selective where ligand rigidity constrains accessibility; in 3b, the ethyl groups are attacked preferentially. The observed relative thermal stabilities and dealkylation selectivities of 1b-9b are correlated with NC(alpha)-H bond dissociation energies, statistical factors, ligand backbone rigidity, and ligand denticity/axial donor strength. Among the peralkylated amines surveyed, bidentate ligands with oxidatively robust NC(alpha)-H bonds provide optimal stabilization for Os. Fortuitously, the least sterically demanding N-alkyl substituent (methyl) gives rise to the most thermally stable and most physically accessible O core, retaining the potential for exogenous substrate reactivity.     

Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation

While Alzheimer''s Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Aβ aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Aβ aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Aβ oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu²⁺ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the ⁶⁴Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the ⁶⁴Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 %ID per g. Overall, by evaluating the various properties of these MFCs valuable structure–activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD.

A series of multifunctional compounds and their ⁶⁴Cu complexes exhibit good affinity for Aβ aggregates and can also control Aβ toxicity.     

Holmium(iii) molecular nanomagnets for optical thermometry exploring the luminescence re-absorption effect

Coordination complexes of lanthanide(3+) ions can combine Single-Molecule Magnetism (SMM) with thermally modulated luminescence applicable in optical thermometry. We report an innovative approach towards high performance SMM-based optical thermometers which explores tunable anisotropy and the luminescence re-absorption effect of Ho^III complexes. Our concept is shown in dinuclear cyanido-bridged molecules, {[Ho^III(4-pyridone)₄(H₂O)₂][M^III(CN)₆]}·nH₂O (M = Co, 1; Rh, 2; Ir, 3) and their magnetically diluted analogues, {[Ho^III_xY^III_1–x(4-pyridone)₄(H₂O)₂][M^III(CN)₆]}·nH₂O (M = Co, x = 0.11, 1@Y; Rh, x = 0.12, 2@Y; Ir, x = 0.10, 3@Y). They are built of pentagonal bipyramidal Ho^III complexes revealing the zero-dc-field SMM effect. Experimental studies and the ab initio calculations indicate an Orbach magnetic relaxation with energy barriers varying from 89.8 to 86.7 and 78.7 cm⁻¹ K for 1, 2, and 3, respectively. 1–3 also differ in the strength of quantum tunnelling of magnetization which is suppressed by hyperfine interactions, and, further, by the magnetic dilution. The Y^III-based dilution governs the optical properties as 1–3 exhibit poor emission due to the dominant re-absorption from Ho^III while 1@Y–3@Y show room-temperature blue emission of 4-pyridone. Within ligand emission bands, the sharp re-absorption lines of the Ho^III electronic transitions were observed. Their strong thermal variation was used in achieving highly sensitive ratiometric optical thermometers whose good performance ranges, lying between 25 and 205 K, are adjustable by using hexacyanidometallates. This work shows that Ho^III complexes are great prerequisites for advanced opto-magnetic systems linking slow magnetic relaxation with unique optical thermometry exploiting a luminescence re-absorption phenomenon.

Ho^III complexes bearing organic luminophores and inorganic metalloligands are an effective tool for achieving the unique conjunction of single-molecule magnetism and thermometric luminescence re-absorption phenomenon.     

Binding sites on the outside of metallo-supramolecular architectures; engineering coordination polymers from discrete architectures

Aggregation of metallo-supramolecular architectures through additional coordination is explored by introducing metal-binding units onto the outside of the supramolecular architectures. This is achieved within the framework of our imine-based approach to supramolecular architecture, by replacing the pyridylimine units with pyrazylketimine units. An advantage of the design is that it retains the ease-of-synthesis which characterises our imine-based approach. Silver(I) complexes of three pyrazylketimine ligand systems are described. The complexes demonstrate that introducing pyrazine donor units does indeed allow higher-order assembly of the distinct supramolecular architectures into engineered coordination polymers. Two distinct types of aggregation are observed. In the first, the donors on the outside of one architecture bind to the metals of another to link the units into a polymeric array. In the second type, the donors on the outside of the architectures bind to separate metal centres which are themselves not part of the architectures, and these separate metal centres link the units to form the macromolecular array. The weaker donor nature of the pyrazine nitrogens (compared to pyridine) also introduces an additional element into the design; higher coordination numbers are favoured and this can lead to arrays with higher connectivity than those observed in the discrete pyridylimine architectures.     

Synthesis and Electrochemical Behavior of Some 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles

Summary. 1H-3-Methyl-4-ethoxycarbonyl-5-(benzylidenehydrazino)pyrazoles are key intermediates in obtaining various heterocyclic systems including pyrazolotriazoles. We present the voltammetric behavior of these compounds in nonaqueous media, with the following para substituents grafted on the benzene ring: –N(CH₃)₂, –OH, –OCH₃, –F, –Cl, –CF₃, –NO₂, as well as of the novel compounds with –Br, –I, and –SCH₃ in the para position, in order to elucidate the influence of the various substituents on the mechanism of anodic oxidation.     

Crystal structures and magnetic properties of a sterically encumbered dithiadiazolyl radical, 2,4,6-(F3C)3C6H2CNSSN.

The sterically protected dithiadiazolyl radical (F3C)3C6H2CNSSN. (1) crystallises in two polymorphs: 1alpha, comprised of monomeric units and 1beta, containing a mixture of both pi*-pi* dimers and S = (1/2) monomers; whilst both polymorphs exhibit similar structure-directing motifs, the variation in packing leads to different magnetic behaviour.     

Refined asymptotic expansions for nonlocal diffusion equations

We study the asymptotic behavior for solutions to nonlocal diffusion models of the form u _t = J * u – u in the whole with an initial condition u(x, 0) = u ₀(x). Under suitable hypotheses on J (involving its Fourier transform) and u ₀, it is proved an expansion of the form

Azulene‐substituted pyridines and pyridinium salts. Synthesis and structure. 1. Azulene‐substituted pyridines

4‐Azulen‐1‐yl substituted 2,6‐dimethyl‐and 2,6‐diphenyl‐pyridines are obtained in good yields from the reaction of corresponding 4‐azulen‐1‐yl‐pyranylium salts and ammonium acetate in ethanol or starting from 4‐chloro‐2,6‐diphenyl‐pyranylium salts in two steps: reaction with azulenes followed by in situ treatment with ammonium acetate. The effect of substitution at the 3‐position of the heterocycle was taken into account. The structure assignment was accomplished with NMR and uv‐vis spectra.