HECTD2 Is Associated with Susceptibility to Mouse and Human Prion Disease

Prion diseases are fatal transmissible neurodegenerative disorders, which include Scrapie, Bovine Spongiform Encephalopathy (BSE), Creutzfeldt-Jakob Disease (CJD), and kuru. They are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. We have used a heterogeneous stock of mice to identify Hectd2, an E3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. Further, we report an association between HECTD2 haplotypes and susceptibility to the acquired human prion diseases, vCJD and kuru. We report a genotype-associated differential expression of Hectd2 mRNA in mouse brains and human lymphocytes and a significant up-regulation of transcript in mice at the terminal stage of prion disease. Although the substrate of HECTD2 is unknown, these data highlight the importance of proteosome-directed protein degradation in neurodegeneration. This is the first demonstration of a mouse quantitative trait gene that also influences susceptibility to human prion diseases. Characterisation of such genes is key to understanding human risk and the molecular basis of incubation periods

Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

Cally Roper and colleagues analyze the distribution of sulfadoxine resistance mutations and flanking microsatellite loci to trace the emergence and dispersal of drug-resistant Plasmodium falciparum malaria in Africa

Solid-State and Solution Metallophilic Aggregation of a Cationic [Pt(NCN)L]⁺ Cyclometalated Complex

The noncovalent intermolecular interactions (π–π stacking, metallophilic bonding) of the cyclometalated complexes [Pt­(NCN)­L]⁺X^– (NCN = dipyridylbenzene, L = pyridine (<b>1</b>), acetonitrile (<b>2</b>)) are determined by the steric properties of the ancillary ligands L in the solid state and in solution, while the nature of the counterion X^– (X^– = PF₆^–, ClO₄^–, CF₃SO₃^–) affects the molecular arrangement of <b>2</b>·X in the crystal medium. According to the variable-temperature X-ray diffraction measurements, the extensive Pt···Pt interactions and π-stacking in <b>2</b>·X are significantly temperature-dependent. The variable concentration ¹H and diffusion coefficients NMR measurements reveal that <b>2</b>·X exists in the monomeric form in dilute solutions at 298 K, while upon increase in concentration [Pt­(NCN)­(NCMe)]⁺ cations undergo the formation of the ground-state oligomeric aggregates with an average aggregation number of ∼3. The photoluminescent characteristics of <b>1</b> and <b>2</b>·X are largely determined by the intermolecular aggregation. For the discrete molecules the emission properties are assigned to metal perturbed IL charge transfer mixed with some MLCT contribution. In the case of oligomers <b>2</b>·X the luminescence is significantly red-shifted with respect to <b>1</b> and originates mainly from the ³MMLCT excited states. The emission energies depend on the structural arrangement in the crystal and on the complex concentration in solution, variation of which allows for the modulation of the emission color from greenish to deep red. In the solid state the lability of the ligands L leads to vapor-induced reversible transformation <b>1</b> ↔ <b>2</b> that is accompanied by the molecular reorganization and, consequently, dramatic change of the photophysical properties. Time-dependent density functional theory calculations adequately support the models proposed for the rationalization of the experimental observations

Chromophore-Functionalized Phenanthro-diimine Ligands and Their Re(I) Complexes

A series of diimine ligands has been designed on the basis of 2-pyridyl-1<i>H</i>-phenanthro­[9,10-<i>d</i>]­imidazole (<b>L1</b>, <b>L2</b>). Coupling the basic motif of <b>L1</b> with anthracene-containing fragments affords the bichromophore compounds <b>L3</b>–<b>L5</b>, of which <b>L4</b> and <b>L5</b> adopt a donor–acceptor architecture. The latter allows intramolecular charge transfer with intense absorption bands in the visible spectrum (lowest λ_abs 464 nm (ε = 1.2 × 10⁴ M^–1 cm^–1) and 490 nm (ε = 5.2 × 10⁴ M^–1 cm^–1) in CH₂Cl₂ for <b>L4</b> and <b>L5</b>, respectively). <b>L1</b>–<b>L5</b> show strong fluorescence in a fluid medium (Φ_em = 22–92%, λ_em 370–602 nm in CH₂Cl₂); discernible emission solvatochromism is observed for <b>L4</b> and <b>L5</b>. In addition, the presence of pyridyl (<b>L1</b>–<b>L5</b>) and dimethylaminophenyl (<b>L5</b>) groups enables reversible alteration of their optical properties by means of protonation. Ligands <b>L1</b>–<b>L5</b> were used to synthesize the corresponding [Re­(CO)₃X­(diimine)] (X = Cl, <b>1</b>–<b>5</b>; X = CN, <b>1</b>-<b>CN</b>) complexes. <b>1</b> and <b>2</b> exhibit unusual dual emission of singlet and triplet parentage, which originate from independently populated ¹ππ* and ³MLCT excited states. In contrast to the majority of the reported Re­(I) carbonyl luminophores, complexes <b>3</b>–<b>5</b> display moderately intense ligand-based fluorescence from an anthracene-containing secondary chromophore and complete quenching of emission from the ³MLCT state presumably due to the triplet–triplet energy transfer (³MLCT → ³ILCT)

Metalated Ir(III) Complexes Based on the Luminescent Diimine Ligands: Synthesis and Photophysical Study

A series of novel diimine (N^∧N) ligands containing developed aromatic [2,1-<i>a</i>]­pyrrolo­[3,2-<i>c</i>]­isoquinoline system have been prepared and used in the synthesis of Ir­(III) luminescent complexes. In organic solvents, the ligands display fluorescence which depends strongly on the nature of solvents to give moderate to strong orange emission in aprotic solvents and shows a considerable blue shift and substantial increase in emission intensity in methanol. Insertion of electron-withdrawing and -donating substituents into peripheral phenyl fragment has nearly no effect onto emission parameters. The ligands were successfully used to prepare the metalated [Ir­(N^∧C)₂(N^∧N)]⁺ complexes (where N^∧C = phenylpyridine (<b>N^∧C-1</b>), <i>p</i>-tolylpyridine (<b>N^∧C-2</b>), 2-(benzo­[<i>b</i>]­thiophen-2-yl)­pyridine (<b>N^∧C-3</b>), 2-benzo­[<i>b</i>]­thiophen-3-yl)­pyridine (<b>N^∧C-4</b>), and methyl 2-phenylquinoline-4-carboxylate (<b>N^∧C-5</b>)) using standard synthetic procedures. The complexes obtained display moderate to strong phosphorescence in organic solvents; the emission characteristics is determined by the nature of emissive triplet state, which varies substantially with the variations in the structure and donor properties of the C- and N-coordinating functions in metalating ligands. TD-DFT calculations show that for complexes <b>1</b>, <b>2</b>, and <b>4</b> the emission originates from the mixed ³MLCT/³LLCT excited states with the major contribution from the aromatic moiety of the diimine ligand, whereas in <b>3</b> the emissive triplet manifold is mainly located at the N^∧C ligand to give structured emission band typical for the ligand centered (LC) excited state. In the case of <b>5</b>, the phosphorescence may be also assigned to the mixed ³MLCT/³LLCT excited state; however, the major contribution is attributed to the aromatic moiety of the metalating N^∧C ligand

Sensitive and selective chromogenic sensing of carbon monoxide via reversible axial CO coordination in binuclear rhodium complexes

The study of probes for CO sensing of a family of binuclear rhodium(II) compounds of general formula [Rh 2{(XC 6H 3)P(XC 6H 4)} n(O 2CR) 4-n]·L 2 containing one or two metalated phosphines (in a head-to-tail arrangement) and different axial ligands has been conducted. Chloroform solutions of these complexes underwent rapid color change, from purple to yellow, when air samples containing CO were bubbled through them. The binuclear rhodium complexes were also adsorbed on silica and used as colorimetric probes for "naked ey" CO detection in the gas phase. When the gray-purple colored silica solids containing the rhodium probes were exposed to air containing increasing concentrations of CO, two colors were observed, in agreement with the formation of two different products. The results are consistent with an axial coordination of the CO molecule in one axial position (pink-orange) or in both (yellow). The crystal structure of 3·(CO) ([Rh 2{(C 6H 4)P(C 6H 5) 2} 2(O 2CCF 3) 2]·CO) was solved by single X-ray diffraction techniques. In all cases, the binuclear rhodium complexes studied showed a high selective response to CO with a remarkable low detection limit. For instance, compound 5· (CH 3CO 2H) 2 ([Rh 2{(m- CH 3C 6H 3)P(m-CH 3C 6H 4) 2} 2(O 2CCH 3) 2]· (CH 3CO 2H) 2) is capable of detection of CO to the "naked ey" at concentrations as low as 0.2 ppm in air. Furthermore, the binding of CO in these rhodium complexes was found to be fully reversible, and release studies of carbon monoxide via thermogravimetric measurements have also been carried out. The importance of the silica support for the maintenance of the CO-displaced L ligands in the vicinity of the probes in a noninnocent manner has been also proved. © 2011 American Chemical Society.The authors wish to express their gratitude to the Spanish Ministerio de Ciencia y e Innovacion (projects MAT2009-14564-C04-01 and CTQ2009-14443-C02-02) and Generalitat Valenciana (project PROMETEO/2009/016) for their support. MEM is grateful to the Spanish Ministerio de Ciencia e Innovacion for an FPU grant.Moragues Pons, ME.; Esteban Moreno, J.; Ros-Lis, JV.; Martínez Mañez, R.; Marcos Martínez, MD.; Martínez, M.; Soto Camino, J.... (2011). Sensitive and selective chromogenic sensing of carbon monoxide via reversible axial CO coordination in binuclear rhodium complexes. Journal of the American Chemical Society. 133:15762-15772. https://doi.org/10.1021/ja206251rS157621577213