Novel M(II) beta-diketiminate complexes for the polymerization of lactide

Des ligands diketimines porteurs de substituants N-benzyl, N-9-anthrylmethyl et N-mesitylmethyl (nacnacBnH, nacnacAnH, and nacnacMesH) ont été synthétisés par condensation d’une amine et d’acétyl acétone ou son monoacétal d’éthylène glycol. La chlorination de la position 3 a été effectuée à l’aide de N-chlorosuccinimide conduisant à la formation des ligands ClnacnacBnH et ClnacnacAnH. Cette même position 3 a également été substituée par un groupement succinimide par lithiation du nacnacBnH, suivi de la réaction avec le N-chlorosuccinimide (3-succinimido-nacnacBnH). Les ligands N-aryl nacnacippH et nacnacNaphH (ipp = 2-isopropylphenyl, Naph = 1-naphthyl) ont été préparés selon les procédures reportées dans la littérature. La réaction de ces ligands avec Zn(TMSA)2 (TMSA = N(SiMe3)2) conduit à la formation des complexes nacnacAnZn(TMSA) et ClnacnacBnZn(TMSA). La protonation avec l’isopropanol permet l’obtention des complexes nacnacAnZnOiPr et ClnacnacBnZnOiPr. La réaction avec Mg(TMSA)2 permet quant à elle la formation des complexes nacnacAnMg(TMSA), nacnacMesMg(TMSA), ClnacnacBnMg(TMSA) et ClnacnacAnMg(TMSA). La protonation subséquente à l’aide du tert-butanol permet l’obtention du nacnacMesMgOtBu et du ClnacnacBnMgOtBu, alors que l’on observe uniquement une décomposition avec les ligands possédant des substituants N-anthrylmethyl. La réaction de ces diketimines avec Cu(OiPr)2 conduit aux dimères hétéroleptiques [nacnacBnCu(μ-OiPr)]2 et [3-Cl-nacnacBnCu(μ-OiPr)]2 lors de l’usage des ligands stériquement peu encombrés. Lors de l’utilisation de ligands plus encombrés, la stabilisation du complexe hétéroleptique par dimérisation n’est plus possible, conduisant, par un échange de ligand, à la formation des complexes homoleptiques Cu(nacnacipp)2 et Cu(nacnacNaph)2. Les complexes homoleptiques Cu(nacnacBn)2 et Cu(3-succinimido-nacnacBn)2 ont été obtenus à partir des ligands N-benzyl. Les ligands encore plus encombrés tels que nacnacAnH, nacnacMesH ou ceux comportant des substituants N-methylbenzyl ne présentent alors plus de réactivité avec le Cu(OiPr)2. La plupart des complexes ont été caractérisés par Diffraction des Rayons X. Les complexes homoleptiques ainsi que ceux de TMSA sont monomériques, alors que ceux formés à partir d’alkoxides se présentent sous forme de dimères à l’état solide. Tous les complexes d’alkoxides ainsi que les nacnacAnMg(TMSA)/BnOH et ClnacnacAnMg(TMSA)/BnOH présentent une réactivité modérée à haute en matière de polymérisation du rac-lactide (90% de conversion en 30 secondes à 3 heures). Le nacnacAnZnOiPr permet la synthèse d’un polymère hautement hétérotactique (Pr = 0.90) quand le ClnacnacBnMgOtBu/BnOH génère un polymère isotactique à -30°C (Pr = 0.43). Tous les autres catalyseurs produisent des polymères atactiques avec une légère tendance hétérotactique (Pr = 0.48 – 0.55). Les complexes hétéroleptiques [nacnacBnCu(μ-OiPr)]2 et [3-Cl-nacnacBnCu(μ-OiPr)]2 se révèlent être de très bons catalyseurs pour la polymérisation du rac-lactide présentant une conversion complète du monomère à température ambiante, en solution, en 0,5 à 5 minutes. Le [nacnacBnCu(μ-OiPr)]2 est actif en présence ou absence d’isopropanol, agissant comme agent de transfert de chaine à haute activité (k2 = 32 M–1•s–1) dans le dichlorométhane. Dans l’acétonitrile, le THF, le dichloromethane et le toluène, [nacnacBnCu(μ-OiPr)]2 conduit à une étroite polydispersité, possédant respectivement des kobs = 2.4(1), 5.3(5), 3.6-4.4 and 10(1) min–1. Aucune réaction parasite, telle qu’une trans-esterification, une épimerisation ou une décomposition du catalyseur, n’a été observée. Les complexes homoleptiques en présence d’alcool libre semblent présenter un équilibre avec une petite quantité de leurs équivalents hétéroleptiques, permettant une polymérisation complète, en moins de 60 min, à température ambiante. Tous les catalyseurs de cuivre présentent un haut contrôle de la polymérisation avec une polydispersité égale ou inférieure à 1.1. Les polymères obtenus sont essentiellement atactiques, avec une légère tendance à l’hétérotacticité à température ambiante et -17°C. Le [nacnacBnCu(μ-OiPr)]2 polymérise également la -butyrolactone (BL), l’-caprolactone (CL) et la -valerolactone (VL) avec des constantes respectivement égales à kobs = 3.0(1)•10–2, 1.2–2.7•10–2, et 0.11(1) min–1. Les homopolymères présentent une étroite polydispersité d’approximativement 1.1. Les polymérisations par addition séquentielle ont mis en évidence une trans-estérification (non observée dans les homopolymérisations) si BL ou CL sont introduits après un bloc lactide.

Syntheses of two new 1D and 3D networks of Cu(II) and Co(II) using malonate and urotropine as bridging ligands: Crystal structures and magnetic studies

Two new metal-organic based polymeric complexes, [Cu-4(O2CCH2CO2)(4)(L)].7H(2)O (1) and [CO2(O2CCH2CO2)(2)(L)].2H(2)O (2) [L = hexamethylenetetramine (urotropine)], have been synthesized and characterized by X-ray crystal structure determination and magnetic studies. Complex 1 is a 1D coordination polymer comprising a carboxylato, bridged Cu-4 moiety linked by a tetradentate bridging urotropine. Complex 2 is a 3D coordination polymer made of pseudo-two-dimensional layers of Co(II) ions linked by malonate anions in syn-anticonformation which are bridged by bidentate urotropine in trans fashion, Complex 1 crystallizes in the orthothombic system, space group Pmmn, with a = 14,80(2) Angstrom, b = 14.54(2) Angstrom, c = 7.325(10) Angstrom, beta = 90degrees, and Z = 4. Complex 2 crystallizes in the orthorhombic system, space group Imm2, a = 7.584(11) Angstrom, b = 15.80(2) Angstrom, c = 6.939(13) Angstrom, beta = 90.10degrees(1), and Z = 4. Variable temperature (300-2 K) magnetic behavior reveals the existence of ferro- and antiferromagnetic interactions in 1 and only antiferromagnetic interactions in 2. The best fitted parameters for complex 1 are J = 13.5 cm(-1), J = -18.1 cm(-1), and g = 2.14 considering only intra-Cu-4 interactions through carboxylate and urotropine pathways. In case of complex 2, the fit of the magnetic data considering intralayer interaction through carboxylate pathway as well as interlayer interaction via urotropine pathway gave no satisfactory result at this moment using any model known due to considerable orbital contribution of Co(II) ions to the magnetic moment and its complicated structure. Assuming isolated Co(II) ions (without any coupling, J = 0) the shape of the chi(M)T curve fits well with experimental data except at very low temperatures.

Signaling mechanisms of GPCR ligands

G protein-coupled receptors constitute one of the major classes of drug targets, so understanding the mechanisms of signaling through these receptors is of great importance. This review covers some of the recent advances in G protein-coupled receptor signaling. A high resolution structure of the beta(2)-adrenergic receptor has been reported, as well as several molecular switches involved in receptor activation. It has also been realised that receptors and G proteins and their subunits may not always separate upon receptor activation. The definition of the ability of these receptors to signal has been expanded considerably with the realisation that some signaling may occur independently of G proteins, that some signaling events may differ in their pharmacological profiles and that formation of heterodimers of these receptors may provide new avenues for both signaling and drug design.

The Thyroid Hormone Receptor (TR) beta-Selective Agonist GC-1 Inhibits Proliferation But Induces Differentiation and TR beta mRNA Expression in Mouse and Rat Osteoblast-Like Cells

Previous studies showed anabolic effects of GC-1, a triiodothyronine (T3) analogue that is selective for both binding and activation functions of thyroid hormone receptor (TR) beta 1 over TR alpha 1, on bone tissue in vivo. The aim of this study was to investigate the responsiveness of rat (ROS17/2.8) and mouse (MC3T3-E1) osteoblast-like cells to GC-1. As expected, T3 inhibited cellular proliferation and stimulated mRNA expression of osteocalcin or alkaline phosphatase in both cell lineages. Whereas equimolar doses of T3 and GC-1 equally affected these parameters in ROS17/2.8 cells, the effects of GC-1 were more modest compared to those of T3 in MC3T3-E1 cells. Interestingly, we showed that there is higher expression of TR alpha 1 than TR beta 1 mRNA in rat (similar to 20-90%) and mouse (similar to 90-98%) cell lineages and that this difference is even higher in mouse cells, which highlights the importance of TR alpha 1 to bone physiology and may partially explain the modest effects of GC-1 in comparison with T3 in MC3T3-E1 cells. Nevertheless, we showed that TR beta 1 mRNA expression increases (similar to 2.8- to 4.3-fold) as osteoblastic cells undergo maturation, suggesting a key role of TR beta 1 in mediating T3 effects in the bone forming cells, especially in mature osteoblasts. It is noteworthy that T3 and GC-1 induced TR beta 1 mRNA expression to a similar extent in both cell lineages (similar to 2- to 4-fold), indicating that both ligands may modulate the responsiveness of osteoblasts to T3. Taken together, these data show that TR beta selective T3 analogues have the potential to directly induce the differentiation and activity of osteoblasts.

Differential effects of TR ligands on hormone dissociation rates: Evidence for multiple ligand entry/exit pathways

Some nuclear receptor (NR) ligands promote dissociation of radiolabeled bound hormone from the buried ligand binding cavity (LBC) more rapidly than excess unlabeled hormone itself This result was interpreted to mean that challenger ligands bind allosteric sites on the LBD to induce hormone dissociation, and recent findings indicate that ligands bind weakly to multiple sites on the LBD surface. Here we show, that a large fraction of thyroid hormone receptor (TR) ligands promote rapid dissociation (T(1/2) < 2 h) of , radiolabeled T(3) vs. T(3) (T(1/2), approximate to 5-7 h). We cannot discern relationships between this effect and ligand size, activity or affinity for TR beta. One ligand, GC-24, binds the TR LBC and (weakly) to the TR beta-LBD surface that mediates dimer/heterodimer interaction, but we cannot link this interaction to rapid T(3) dissociation. Instead, several lines of evidence suggest that the challenger ligand must interact with the buried LBC to promote rapid T(3) release. Since previous molecular dynamics simulations suggest that TR ligands leave the LBC by several routes, we propose that a subset of challenger ligands binds and stabilizes a partially unfolded intermediate state of TR that arises during T(3) release and that this effect enhances hormone dissociation. (C) 2009 Elsevier Ltd. All rights reserved.

Ligand induced interaction of thyroid hormone receptor beta with its coregulators

Thyroid hormones exert most of their physiological effects through two thyroid hormone receptor (TR) subtypes, TR alpha and TR beta, which associate with many transcriptional coregulators to mediate activation or repression of target genes. The search for selective TR beta ligands has been stimulated by the finding that several pharmacological actions mediated by TR beta might be beneficial in medical conditions such as obesity, hypercholesterolemia and diabetes. Here, we present a new methodology which employs surface plasmon resonance to investigate the interactions between TR beta ligand binding domain (LBD) complexes and peptides derived from the nuclear receptor interaction motifs of two of its coregulators, SRC2 and DAX1. The effect of several TR beta ligands, including the TR beta selective agonist GC-I and the TR beta selective antagonist NH-3, were investigated. We also determined the kinetic rate constants for the interaction of TR beta-T3 with both coregulators, and accessed the thermodynamic parameters for the interaction with DAX1. Our findings Suggest that flexibility plays an important role in the interaction between the receptor and its coregulators. and point out important aspects of experimental design that should be addressed when using TR beta LBD and its agonists. Furthermore, the methodology described here may be useful for the identification of new TR beta ligands. (C) 2008 Elsevier Ltd. All rights reserved.

New Pd(II) and Pt(II) complexes with N,S-chelated pyrazolonate ligands: Molecular and supramolecular structure and preliminary study of their in vitro antitumoral activity

New Pd(II) and Pt(II) complexes [ML2] (HL = a substituted 2,5-dihydro-5-oxo-1H-pyrazolone-1-carbothioamide) have been synthesized by reacting K2MCl4 (M = Pd, Pt) or Pd(OAc)(2) with beta-ketoester thiosemicarbazones. The structures of seven of these complexes were determined by X-ray diffraction. Although all exhibit a distorted square-planar coordination with trans- or (in one case) cis-[MN2S2] kernels, their supramolecular arrangements vary widely from isolated molecules to 3D-networks. The in vitro antitumoral assays performed with two HL ligands and their metal complexes showed significant cytostatic activity for the latter, with the most active [ML2] derivative (a palladium complex) being about sixteen times more active than cis-DDP against the cis-platinum-resistant cell line A2780cisR. (c) 2007 Elsevier Inc. All rights reserved.

Practical synthesis of chiral beta-telluro amines by ring-opening reaction of aziridines

A set of chiral beta-tellurium amines and their selenium and sulfur-containing derivatives have been efficiently synthesized in good to excellent yields via the ring-opening reaction of chiral aziridines by chalcogen nucleophilic species. (C) 2008 Elsevier B.V. All rights reserved.

Electroluminescent devices based on rare-earth tetrakis beta-diketonate complexes

In this paper the synthesis, photo luminescence and electroluminescence investigation of the novel tetrakis beta-diketonate of rare-earth complexes such as M[Eu(dbM)(4)] and M[Tb(acac)(4)] with a variety of cationic ligands, M=Li(+), Na(+) and K(+) have been investigated. The emission spectra of the Eu(3+) and Tb(3+) complexes displayed characteristic narrow bands arising from intraconfigurational transitions of trivalent rare-earth ions and exhibited red color emission for the Eu(3+) ion ((5)D(0) -> F(J), J=0-6) and green for the Tb(3+) ion ((5)D(4) -> (7)F(J), J = 6-0). The lack of the broaden emission bands arising from the ligands suggests the efficient intramolecular energy transfer from the dbm and acac ligands to Eu(3+) and Tb(3+) ions, respectively. In accordance to the expected, the values of PL quantum efficiency (eta) of the emitting (5)D(0) state of the tetrakis(beta-diketonate) complexes of Eu(3+) were higher compared with those tris-complexes. Therefore, organic electroluminescent (EL) devices were fabricated with the structure as follows: indium tin oxide (ITO)/hole transport layer (HTL) NPB or MTCD/emitter layer M[RE(beta-diketonate)(4)] complexes)/Aluminum (Al). All the films were deposited by thermal evaporation carried out in a high vacuum environment system. The OLED light emission was independent of driving voltage, indicating that the combination of charge carriers generates excitons within the M[RE(beta-diketonate)(4)] layers, and the energy is efficiently transferred to RE(3+) ion. As a best result, a pure red and green electroluminescent emission was observed from the Eu(3+) and Tb(3+) devices, confirmed by (X,Y) color coordinates. (C) 2008 Elsevier B.V. All rights reserved.

Synthesis of substituted alpha,beta-unsaturated delta-lactones from vinyl tellurides

A new approach for the synthesis of alpha,beta-unsaturated delta-lactones, a unit present in many natural products with interesting biological activities is described. The approach was based on the use of a vinyl telluride, and it is complementary to the methods using ring-closing metathesis. The sequence was performed in good overall yield with retention of the Z-double bond geometry. (C) 2011 Elsevier Ltd. All rights reserved.

Structure of human PNP complexed with ligands

Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage pathway, which allows cells to utilize preformed bases and nucleosides in order to synthesize nucleotides. PNP is specific for purine nucleosides in the beta-configuration and exhibits a strong preference for purines containing a 6-keto group and ribosyl-containing nucleosides relative to the corresponding analogues. PNP was crystallized in complex with ligands and data collection was performed using synchrotron radiation. This work reports the structure of human PNP in complex with guanosine (at 2.80 angstrom resolution), 3' deoxyguanosine (at 2.86 angstrom resolution) and 8-azaguanine (at 2.85 angstrom resolution). These structures were compared with the PNP-guanine, PNP-inosine and PNP-immucillin-H complexes solved previously.

New phosphinate ligand synthesis and its effect on optical properties of the europium beta-diketonate complex

The synthesis and characterization of a new organic ligand monooctyldiphenylphosphinate (L) is described, as well as a new Eu(3+) diketonate complex [Eu(tta)(3)(L)(2)] (tta = thenoyltrifluoracetone). The ligand (L) was formed by substitution reaction (80% yield) and characterized by uni- and bidimensional (1)H, (13)C and (31)P NMR experiments, to confirm its molecular structure. The coordination of (L) to Eu(3+) in the complex [Eu(tta)(3)(L)(2)] was confirmed by FT-IR spectra. The emission spectra present the same profile when excited in Eu(3+) or in the ligands, suggesting an energy transfer from ligands to Eu(3+) ions. The emission spectra of the precursor [Eu(tta)(3)(H(2)O)(2)], and [Eu(tta)(3)(L(2))] present bands arising from f-f intra-configurational transitions. The only (5)D(0)-(7)F(0) transition shows the presence of at least one site without symmetry center. The FWHM of such transition is 7 cm(-1) and 57 cm(-1) for [Eu(tta)(3)(H(2)O)(2)] and [Eu(tta)(3)(L)(2)] complexes, respectively. This widening is provided by the presence of large groups around Eu(3+) ion. The calculated intensity parameters Omega(2) and Omega(4) show that the interaction features between center-ion and ligand are different; the small value of Omega(4) is related to long range effects of alkyl chain. The Langmuir isotherms of this ligand and complex have been investigated although their hydrolysis in water subphase does not allow stable monolayers. (C) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis and thermal characterization of luminescent powers of terbium(III) with mixed ligands

This work deals with the synthesis and thermal decomposition of complexes of general formula: Ln(beta-dik)(3)L (where Ln=Tb(+3), beta-dik=4,4,4-trifluoro-1-phenyl-1,3butanedione(btfa) and L=1,10-fenantroline(phen) or 2,2-bipiridine(bipy). The powders were characterized by melting point, FTIR spectroscopy, LTV-visible, elemental analysis, scanning differential calorimeter(DSC) and thermogravimetry(TG). The TG/DSC curves were obtained simultaneously in a system DSC-TGA, under nitrogen atmosphere. The experimental conditions were: 0.83 ml.s(-1) carrier gas flow, 2.0 +/- 0.5 mg samples and 10 degrees C.min(-1) heating rate. The CHN elemental analysis of the Tb(btfa)(3)bipy and Tb(btfa)(3)phen complexes, are in good agreement with the expected values. The IR spectra evinced that the metal ion is coordinated to the ligands via C=O and C-N groups. The TG/DTG/DSC curves of the complexes show that they decompose before melting. The profiles of the thermal decomposition of the Tb(btfa)3phen and Tb(btfa)3bipy showed six and five decomposition stages, respectively. Our data suggests that the thermal stability of the complexes under investigation followed the order: Tb(btfa)(3)phen < Tb(btfa)(3)bipy.

Electroluminescence of a device based on europium beta-diketonate with phosphine oxide complex

Rare earth (RE) ions have spectroscopic characteristics to emit light in narrow lines, which makes RE complexes with organic ligands candidates for full color OLED (Organic Light Emitting Diode) applications. In particular, beta-diketone rare earth (RE(3+)) complexes show high fluorescence emission efficiency due to the high absorption coefficient of the beta-diketone and energy transfer to the central ion. In this work, the fabrication and the electroluminescent properties of devices containing a double and triple-layer OLED using a new beta-diketone complex, [Eu(bmdm)(3)(tppo)(2)], as transporting and emitting layers are compared and discussed. The double and triple-layer devices based on this complex present the following configurations respectively: device 1: ITO/TPD (40 nm)/[Eu(bmdm)(3)(tppo)(2)] (40 nm)/Al (150 nm); device 2: ITO/TPD (40 nm)/[Eu(bmdm)(3) (tppo)(2)] (40 nm)/Alq(3) (20 nm)/Al (150 nm) and device 3: ITO/TPD (40 nm)/bmdm-ligand (40 nm)/Al (150 nm), were TPD is (N,N'-diphenyl-N,N'-bis(3-methylphenyl)-1,1-biphenil-4,4-diamine) and bmdm is butyl methoxy-dibenzoyl-methane. All the films were deposited by thermal evaporation carried out in a high vacuum system. These devices exhibit high intensity photo- (PL) and electro-luminescent (EL) emission. Electroluminescence spectra show emission from Eu(3+) ions attributed to the (5)D(0) to (7)F(J) (J = 0, 1, 2, 3 and 4) transitions with the hypersensitive (5)D(o) -> (7)F(2) transition (around 612 nm) as the most prominent one. Moreover, a transition from (5)D(1) to (7)F(1) is also observed around 538 nm. The OLED light emission was almost linear with the current density. The EL CIE chromaticity coordinates (X = 0.66 and Y = 0.33) show the dominant wavelength, lambda(d) = 609 nm, and the color gamut achieved by this device is 0.99 in the CIE color space. (c) 2006 Elsevier B.V. All rights reserved.

Complexos aniônicos contendo európio ou gandolínio e beta-dicetonas aplicados aos estudos foto e/ou eletroluminescentes de sólidos e filmes

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