Uranium halide complexes in ionic liquids

We report here the syntheses, characterisation and electrochemistry of some 1-ethyl-3-methylimidazolium, [emim], uranium halide salts. The electrochemistry of the uranium halide salts were investigated in both basic and acidic haloaluminate ionic liquids (ILs). The solid state structures of the uranium chloride salts have previously been reported, but have now been re-evaluted using a new statistical model to determine the presence or absence of weak hydrogen bonding interactions in the crystalline state.

Multiple Evidence for Gold(I)center dot center dot center dot Silver(I) Interactions in Solution

[AuAg3(C6F5)(CF3CO2)(3)(CH2PPh3)](n) (2) was prepared by reaction of [Au(C6F5)(CH2PPh3)] (1) and [Ag(CF3CO2)] (1:3). The crystal structures of complexes I and 2 were determined by X-ray diffraction, and the latter shows a polymeric 2D arrangement built by Au - Ag, Ag - Ag, and Ag - O contacts. The metallophilic interactions observed in 2 in the solid state seem to be preserved in concentrated THF solutions, as suggested by EXAFS, pulsed-gradient spin-echo NMR, and photophysical studies, which showed that the structural motif [AuAg3(C6F5)(CF3CO2)(3)(CH2PPh3)] is maintained under such conditions. Time-dependent DFT calculations agree with the experimental photophysical energies and suggest a metal-to-ligand charge-transfer phosphorescence process. Ab initio calculations give an estimated interaction energy of around 60 kJ mol(-1) for each Au - Ag interaction.

Long-lived near-infrared luminescent lanthanide complexes of imidodiphosphinate

Near-infrared emitting complexes of Nd(III), Er(III), and Yb(III) based on hexacoordinate lanthanide ions with an aryl functionalized imidodiphosphinate ligand, tpip, have been synthesized and fully characterized. Three tpip ligands form a shell around the lanthanide with the ligand coordinating via the two oxygens leading to neutral complexes, Ln(tpip)(3). In the X-ray crystal structures of Er(III) and Nd(III) complexes there is evidence of CH-pi interactions between the phenyl groups. Photophysical investigations of solution samples of the complexes demonstrate that all complexes exhibit relatively long luminescence lifetimes in nondeuteurated solvents. Luminescence studies of powder samples have also been recorded for examination of the properties of NIR complexes in the solid state for potential material applications. The results underline the effective shielding of the lanthanide by the twelve phenyl groups of the tpip ligands and the reduction of high-energy vibrations in close proximity to the lanthanide, both features important in the design of NIR emitting lanthanide complexes.

Study of the luminescence of tris(2-thenoyltrifluoroacetonato)lanthanide(III) complexes covalently linked to 1,10-phenanthroline-functionalized hybrid sol-gel glasses

The solubility and uniform distribution of lanthanide complexes in sol-get glasses can be improved by covalently linking the complexes to the sol-gel matrix. In this study, several lanthanide beta-diketonate complexes (Ln = Nd, Sm, Eu, Tb, Er, Yb) were immobilized on a 1,10-phenanthroline functionalized sol-gel glass. For the europium(Ill) complex, a sol-gel material of diethoxydimethylsilane (DEDMS) with polymer-like properties was derived. For the other lanthanide complexes, the sol-gel glass was prepared by using a matrix of tetramethoxysilane (TMOS) and DEDMS. Both systems were prepared under neutral reaction conditions. High-resolution emission and excitation spectra were recorded. The luminescence lifetimes were measured. (c) 2004 Elsevier B.V. All rights reserved.

Bis(trifluoromethyl)mercury(II) complexes with purine and 3,5-dimethyl-4 '-amino-triazole as ligands, [Hg(CF3)(2)(Pur)](4) and [Hg(CF3)(2)(Dat)](2)

Colourless single crystals of [Hg(CF3)(2)(Pur)](4) and [Hg(CF3)(2)(Dat)](2) were obtained from aqueous and etheric solutions of the respective components Purine, (imidazo[4,5-d]pyrimidine, Pur), 3,5-dimethyl-4 '-amino-triazole (Dat) and bis(trifluoromethyl)mercury(II), Hg(CF3)(2). [Hg(CF3)(2)(Pur)](4) crystallizes with the tetragonal system (P-4, Z = 8, a = 1486.8(2), c = 1026.2(l) pm, R-all = 0.0657) with tetrameric molecules consisting of four purine molecules bridged by slightly bent Hg(CF3)2 molecules forming a cage with the CF3 ligands surrounding this cage. The two modifications of [Hg(Dat)(CF3)2]2 (1: 170 K, triclinic, P-1, Z = 2, a 814.9(2), b = 845.4(2), c = 968.4(3) pm, alpha = 106.55(2)degrees, beta= 103.41(2)degrees, gamma = 110.79(2)degrees, R-all = 0.1189; II: monoclinic, P2(1)/c, Z = 8, a = 879.8(2), b = 1731.0(3), c = 1593.9(3) pm, beta = 106.89(2)degrees, R-all = 0.1199) both contain dimeric molecules that are stacked parallel to one crystal axis to strands which are arranged in a parallel fashion in I and rotated against each other in 11 by 110 degrees. In both, the tetrameric [Hg(CF3)(2)(Pur)](4) and the dimeric [Hg(CF3)(2)(Dat)](2) the Hg(CF3)(2) molecules are slightly bent (around 167 and 170 degrees) and rather weakly attached to the N-donor ligands Pur and Dat with Hg-N distances around 272 pm, although in both cases the Hg atoms bridge between two ligand molecules.

MEASUREMENT OF SUPEROXIDE FORMATION BY MITOCHONDRIAL COMPLEX I OF YARROWIA LIPOLYTICA

Complex I (NADH: ubiquinone oxidoreductase) is generally regarded as one of the major sources of mitochondrial reactive oxygen species (ROS). Mitochondrial membranes from the obligate aerobic yeast Yarrowia lipolytica, as well as the purified and reconstituted enzyme, can be used to measure complex I-dependent generation of superoxide (O-2(center dot-)). The use of isolated complex I excludes interference with other respiratory chain complexes and matrix enzymes during superoxide dismutase-sensitive reduction of acetylated cytochrome c. Alternately. hydrogen peroxide formation can be measured by the Amplex Red/horseradish peroxidase assay. Both methods allow the determination of complex I-generated ROS, depending on substrates (NADH, artificial ubiquinones), membrane potential, and active/deactive transition. ROS production by Yorrowia complex I in the

Partial agonism, neutral antagonism, and inverse agonism at the human wild-type and constitutively active cholecystokinin-2 receptors

Cholecystokinin receptor-2 (CCK2R) is a G protein receptor that regulates a number of physiological functions. Activation of CCK2R and/or expression of a constitutively active CCK2R variant may contribute to human diseases, including digestive cancers. Search for antagonists of the CCK2R has been an important challenge during the last few years, leading to discovery of a set of chemically distinct compounds. However, several early-discovered antagonists turned out to be partial agonists. In this context, we carried out pharmacological characterization of six CCK2R antagonists using COS-7 cells expressing the human CCK2R or a CCK2R mutant having a robust constitutive activity on inositol phosphates production, and we investigated the molecular mechanisms which, at a CCK2R binding site, account for these features. Results indicated that three compounds, 3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3- yl)-N'-(3-methylphenyl)urea (L365,260), 4-{[2-[[3-(lH-indol-3-yl)-2- methyl-1-oxo-2-[[[1.7.7-trimethyl-bicyclo[2.2.1]hept-2-yl)-oxy]carbonyl]amino] propyl]amino]-1-phenylethyl]amino-4-oxo-[lS-la.2[S*(S*)]4a]} -butanoate N-methyl-D-glucamine (PD135, 158), and (R)-1-naphthalenepropanoic acid, b-[2-[[2-(8-azaspiro-[4.5]dec-8-ylcarbonyl)-4,6-dimethylphenyl]amino]-2- oxoethyl] (CR2945), were partial agonists; one molecule, 1-[(R)-2,3-dihydro-1- (2,3-dihydro-1-(2-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl] -3-(3-methylphenyl)urea (YM022), was a neutral antagonist; and two compounds, N-(+)-[1-(adamant-1-ylmethyl)-2,4-dioxo-5-phenyl2,3,4,5-tetrahydro-1H-1, 5-benzodiazepin-3-yl]-N'-phenylurea (GV150,013X) and ([(N-[methoxy-3 phenyl] N-[N-methyl N-phenyl carbamoylmethyl], carbomoylmethyl)-3 ureido]-3-phenyl)2-propionic acid (RPR101,048), were inverse agonists. Furthermore, target- and pharmacophore-based docking of ligands followed by molecular dynamic simulation experiments resulted in consistent motion of aromatic residues belonging to a network presumably important for activation, thus providing the first structural explanations for the different pharmacological profiles of tested compounds. This study confirms that several referenced so-called antagonists are in fact partial agonists, and because of this undesired activity, we suggest that newly generated molecules should be preferred to efficiently block CCK2R-related physiological effects. Furthermore, data on the structural basis for the different pharmacological features of CCK2R ligands will serve to further clarify CCK2R mechanism of activation. Copyright © 2006 The American Society for Pharmacology and Experimental Therapeutics.

Altered interactions within FY/AtCPSF complexes required for Arabidopsis FCA-mediated chromatin silencing.

The role of RNA metabolism in chromatin silencing is now widely recognized. We have studied the Arabidopsis RNA-binding protein FCA that down-regulates an endogenous floral repressor gene through a chromatin mechanism involving histone demethylase activity. This mechanism needs FCA to interact with an RNA 3' processing/polyadenylation factor (FY/Pfs2p), but the subsequent events leading to chromatin changes are unknown. Here, we show that this FCA-FY interaction is required for general chromatin silencing roles where hairpin transgenes induce DNA methylation of an endogenous gene. We also show 2 conserved RNA processing factors, AtCPSF100 and AtCPSF160, but not FCA, are stably associated with FY in vivo and form a range of different-sized complexes. A hypomorphic fy allele producing a shorter protein, able to provide some FY functions but unable to interact with FCA, reduces abundance of some of the larger MW complexes. Suppressor mutants, which specifically disrupt the FY motif through which FCA interacts, also lacked these larger complexes. Our data support a model whereby FCA, perhaps after recognition of a specific RNA feature, transiently interacts with FY, an integral component of the canonical RNA 3' processing machinery, changing the interactions of the different RNA processing components. These altered interactions would appear to be a necessary step in this RNA-mediated chromatin silencing.

Intrinsic variability in the detection of micrometastases in lymph nodes for re-staging of colorectal cancer: effect of individual markers and tissue samples

In this study, we investigated whether (a) carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20) and guanylyl cyclase C (GCC) are clinically useful markers for the molecular detection of submicroscopic metastases in colorectal cancer (CRC) and (b) whether overexpression of CEA, CK-20 and GCC can be reliably detected in formalin-fixed, paraffin-embedded tissues as well as frozen lymph nodes. We studied 175 frozen lymph nodes and 158 formalin-fixed, paraffin-embedded lymph nodes from 28 cases of CRC. CEA or CK-20 or GCC-specific polymerase chain reaction (PCR) was carried out on mRNA transcripts extracted from the nodal tissues. Ten out of I I Dukes' B CRC cases had detectable CEA and CK-20 while 6 out of 11 Dukes' B CRC cases had detectable GCC. In general, the difference of re-staged cases when comparing frozen and paraffin-embedded samples was marked; the only statistically significant correlation between frozen and paraffin tissue was for the CEA marker. Our results indicated a high incidence (>50%) of detecting micrometastases in histologically-negative lymph nodes at the molecular level. (C) 2003 Elsevier Science Ltd. All rights reserved.

BRD7, a subunit of SWI/SNF complexes, binds directly to BRCA1 and regulates BRCA1-dependent transcription

We carried out a yeast two-hybrid screen using a BRCA1 bait composed of amino acids 1 to 1142 and identified BRD7 as a novel binding partner of BRCA1. This interaction was confirmed by coimmunoprecipitation of endogenous BRCA1 and BRD7 in T47D and HEK-293 cells. BRD7 is a bromodomain containing protein, which is a subunit of PBAF-specific Swi/Snf chromatin remodeling complexes. To determine the functional consequences of the BRCA1-BRD7 interaction, we investigated the role of BRD7 in BRCA1-dependent transcription using microarray-based expression profiling. We found that a variety of targets were coordinately regulated by BRCA1 and BRD7, such as estrogen receptor alpha (ERalpha). Depletion of BRD7 or BRCA1 in either T47D or MCF7 cells resulted in loss of expression of ERalpha at both the mRNA and protein level, and this loss of ERalpha was reflected in resistance to the antiestrogen drug fulvestrant. We show that BRD7 is present, along with BRCA1 and Oct-1, on the ESR1 promoter (the gene which encodes ERalpha). Depletion of BRD7 prevented the recruitment of BRCA1 and Oct-1 to the ESR1 promoter; however, it had no effect on the recruitment of the other Swi/Snf subunits BRG1, BAF155, and BAF57 or on RNA polymerase II recruitment. These results support a model whereby the regulation of ERalpha transcription by BRD7 is mediated by its recruitment of BRCA1 and Oct-1 to the ESR1 promoter.

Asymmetric Carbon-Carbon Bond Forming Reactions Catalysed by Metal(II) Bis(oxazoline) Complexes Immobilized using Supported Ionic Liquids

A series of bis(oxazoline) metal(II) complexes has been supported on silica and carbon supports by non-covalent immobilisation using an ionic liquid. The catalytic performance of these solids was compared for the enantioselective Diels-Alder reaction between N-acryloyloxazolidinone and cyclopentadiene and the Mukaiyama-aldol reaction between methyl pyruvate and 1-methoxy-1-trimethylsilyloxy-propene. In both reactions the enantioselectivity was strongly influenced by the choice of support displaying enantioselectivies (ee values) up to 40% higher than those conducted under homogeneous reaction conditions.

Structure of Adenine on Metal Nanoparticles: pH Equilibria and Formation of Ag+ Complexes Detected by Surface-Enhanced Raman Spectroscopy

The SERS spectra of adenine recorded under a broad range of pH values and concentrations using both silver and gold colloids provided evidence for the existence of several distinct species. At high concentration (0.5-10 ppm), the spectra recorded between pH 1 and 11 showed only two distinct spectra, rather than the three forms that would be expected for a compound with two pK(a) values of 4.2 and 9.8. The spectra at neutral and alkaline pH were identical and assigned to the deprotonated form of adenine on the basis of DFT calculations, isotope shifts, and comparison with the normal Raman spectra of neutral and deprotonated adenine. The spectra at acidic pH were different, consistent with adenine protonation. Neutral adenine was not detected at any pH studied. At low adenine concentration (

Synthesis and characterisation of new platinum-acetylide complexes containing diimine ligands

A new class of platinum-bipyridyl compounds has been synthesized by the dehydrohalogenative reaction of [4,4'-bis(tert-butyl)-2,2'-bipyridyl]platinum dichloride [PtCl2((t)Bu(2)bipy)] 1 with terminal alkynes HC=CR, in the presence of copper(I) iodide and diisopropylamine. The products [Pt(C=CR)(2)((t)Bu(2)bipy)] (R=C6H4NO2-p 2, C6H5 3, C6H4CH3-p 4 or SiMe3 5), have been characterised by spectroscopic and analytical methods, and a single crystal molecular structure determination has been carried out on 4. Extended Huckel molecular orbital calculations have also been carried out, and the results are used to help rationalise the voltammetric, EPR and spectroelectrochemical properties of the new compounds. These show that compounds 3, 4 and 5 undergo a one-electron bipyridyl based redox process, but that 2 has an unresolved two-electron process located on the nitro groups.