Ligand-centred reactivity of bis(picolyl)amine iridium: sequential deprotonation, oxidation and oxygenation of a "non-innocent" ligand

Treatment of [Ir(bpa)(cod)](+) complex [1](+) with a strong base (e.g., tBuO(-)) led to unexpected double deprotonation to form the anionic [Ir-(bpa-2H)(cod)](-) species [3](-), via the mono-deprotonated neutral amido complex [Ir(bpa-H)(cod)] as an isolable intermediate. A certain degree of aromaticity of the obtained metal-chelate ring may explain the favourable double deprotonation. The rhodium analogue [4](-) was prepared in situ. The new species [M(bpa-2H)(cod)](-) (M = Rh, Ir) are best described as two-electron reduced analogues of the cationic imine complexes [M-I(cod)(Py-CH2-N=CH-Py)](+). One-electron oxidation of [3](-) and [4](-) produced the ligand radical complexes [3]* and [4]*. Oxygenation of [3](-) with O-2 gave the neutral carboxamido complex [Ir(cod)(py-CH2-N-CO-py)] via the ligand radical complex [3]* as a detectable intermediate.

Hydroxyamidinates et polymères de coordination : suspicions et valences mixtes

Dans un contexte où l’énergie représente un enjeu majeur pour les pays et organisations à économies émergentes et développées, la recherche de nouvelles sources renouvelables et la démocratisation des vecteurs énergétiques permettant l’approvisionnement mondial de façon durable constitue un devoir pour la communauté scientifique internationale. D’ailleurs, il serait essentiel que les nombreuses disciplines de la chimie concertent leurs efforts. Plus particulièrement, la croissance de la recherche en chimie de coordination orientée vers la photosynthèse artificielle ainsi que le développement de matériaux fonctionnels démontre l’importance indéniable de ce champ de recherche. Ce travail présente dans un premier temps l’étude des différentes voies de synthèse d’hydroxyamidines, un ligand chélatant aux propriétés de coordination prometteuses ne recevant que très peu d’attention de la part de la communauté scientifique. Dans un deuxième temps, nous présenterons le développement d’une stratégie d’assemblage de leurs complexes supramoléculaires impliquant des métaux de transition abondants et peu dispendieux de la première rangée. Dans un troisième temps, il sera question de l’investigation de leurs propriétés photophysiques et électrochimiques à des fins d’applications au sein de matériaux fonctionnels. Pour ce faire, les différentes voies de synthèse des hydroxyamidines et de leurs amidines correspondantes qui ont précédemment été étudiées par les membres du groupe seront tout d’abord perfectionnées, puis investiguées afin de déterminer leur versatilité. Ensuite, les propriétés de complexation des amox résultantes comportant des motifs sélectionnés seront déterminées pour enfin étudier les propriétés photophysiques et électrochimiques d’une série de complexes de métaux de transition de la première rangée. En somme, plusieurs designs qu’offrent les amox et bis-amox sont étudiés et les propriétés des architectures résultantes de leur auto-assemblage sont déterminées.

Hydroxyamidinates et polymères de coordination : suspicions et valences mixtes

Dans un contexte où l’énergie représente un enjeu majeur pour les pays et organisations à économies émergentes et développées, la recherche de nouvelles sources renouvelables et la démocratisation des vecteurs énergétiques permettant l’approvisionnement mondial de façon durable constitue un devoir pour la communauté scientifique internationale. D’ailleurs, il serait essentiel que les nombreuses disciplines de la chimie concertent leurs efforts. Plus particulièrement, la croissance de la recherche en chimie de coordination orientée vers la photosynthèse artificielle ainsi que le développement de matériaux fonctionnels démontre l’importance indéniable de ce champ de recherche. Ce travail présente dans un premier temps l’étude des différentes voies de synthèse d’hydroxyamidines, un ligand chélatant aux propriétés de coordination prometteuses ne recevant que très peu d’attention de la part de la communauté scientifique. Dans un deuxième temps, nous présenterons le développement d’une stratégie d’assemblage de leurs complexes supramoléculaires impliquant des métaux de transition abondants et peu dispendieux de la première rangée. Dans un troisième temps, il sera question de l’investigation de leurs propriétés photophysiques et électrochimiques à des fins d’applications au sein de matériaux fonctionnels. Pour ce faire, les différentes voies de synthèse des hydroxyamidines et de leurs amidines correspondantes qui ont précédemment été étudiées par les membres du groupe seront tout d’abord perfectionnées, puis investiguées afin de déterminer leur versatilité. Ensuite, les propriétés de complexation des amox résultantes comportant des motifs sélectionnés seront déterminées pour enfin étudier les propriétés photophysiques et électrochimiques d’une série de complexes de métaux de transition de la première rangée. En somme, plusieurs designs qu’offrent les amox et bis-amox sont étudiés et les propriétés des architectures résultantes de leur auto-assemblage sont déterminées.

Electrochemical reductive deprotonation of an imidazole ligand in a bipyridine tricarbonyl rhenium(I) complex

The reduction path of the complex fac-[ReΙ(imH)(CO)3(bpy)]+ was studied in situ by UV-Vis-NIR-IR spectroelectrochemistry within an OTTLE cell. The complex undergoes 1e‒ reduction of the 2,2'-bipyridine (bpy) ligand and intramolecular electron transfer resulting in the conversion of the axial imidazole (imH) ligand to 3-imidazolate (3-im–). This step is followed by two bpy-based 1e– reductions producing ultimately the five-coordinate complex [Re(CO)3(bpy)]‒ and free 3-im‒. The identity of the reduction product fac-[Re(3-im–)(CO)3(bpy)] has been proven by partial chemical deprotonation of the parent complex followed by IR spectroelectrochemistry. This is the first time when an electrochemical conversion of metal-coordinated imidazole to terminal 3-imidazolate has been observed.

Preparation, characterization and structure of ruthenium phosphine complexes containing non-innocent ligands

Phosphine ruthenate complexes containing the non-innocent ligands 4-chloro-1,2-phenylenediamine (opda-CI) and 3,3',4,4'-tetraamminebiphenyl (diopda) were synthesized and characterized by means of X-ray diffraction, electrochemistry, P-31{H-1} NMR and electronic spectroscopies. Crystals of cis-[RuCl2 (dppb)(bqdi-CI)] complex were isolated as a mixture of two conformational isomers due to different positions of the chlorine atoms of the o-phenylene ligand in relation to the P1 atom of the phosphine moiety. (C) 2011 Elsevier Ltd. All rights reserved.

Electrocatalytic oxidation of methanol by the [Ru3O(OAc)6(py)2(CH3OH)]3+cluster: improving the metal-ligand electron transfer by accessing the higher oxidation states of a multicentered system

The [Ru3O(Ac)6(py)2(CH3OH)]+ cluster provides an effective electrocatalytic species for the oxidation of methanol under mild conditions. This complex exhibits characteristic electrochemical waves at -1.02, 0.15 and 1.18 V, associated with the Ru3III,II,II/Ru3III,III,II/Ru 3III,III,III /Ru3IV,III,III successive redox couples, respectively. Above 1.7 V, formation of two RuIV centers enhances the 2-electron oxidation of the methanol ligand yielding formaldehyde, in agreement with the theoretical evolution of the HOMO levels as a function of the oxidation states. This work illustrates an important strategy to improve the efficiency of the oxidation catalysis, by using a multicentered redox catalyst and accessing its multiple higher oxidation states.

Spectroscopic characterization and investigation of the dynamic of charge compensation process of supramolecular films derived from tetra-2-pyridyl-1,4-pyrazine ligand

This work describes the infrared spectroscopy characterization and the charge compensation dynamics in supramolecular film FeTPPZFeCN derived from tetra-2-pyridyl-1,4-pyrazine (TPPZ) with hexacyanoferrate, as well as the hybrid film formed by FeTPPZFeCN and polypyrrole (PPy). For supramolecular film, it was found that anion flux is greater in a K+ containing solution than in Li+ solution, which seems to be due to the larger crystalline ionic radius of K+. The electroneutralization process is discussed in terms of electrostatic interactions between cations and metallic centers in the hosting matrix. The nature of the charge compensation process differs from others modified electrodes based on Prussian blue films, where only cations such as K+ participate in the electroneutralization process. In the case of FeTPPZFeCN/PPy hybrid film, the magnitude of the anions’s flux is also dependent on the identity of the anion of the supporting electrolyte.

Genetic variability and natural selection at the ligand domain of the Duffy binding protein in brazilian Plasmodium vivax populations

Background: Plasmodium vivax malaria is a major public health challenge in Latin America, Asia and Oceania, with 130-435 million clinical cases per year worldwide. Invasion of host blood cells by P. vivax mainly depends on a type I membrane protein called Duffy binding protein (PvDBP). The erythrocyte-binding motif of PvDBP is a 170 amino-acid stretch located in its cysteine-rich region II (PvDBP(II)), which is the most variable segment of the protein. Methods: To test whether diversifying natural selection has shaped the nucleotide diversity of PvDBP(II) in Brazilian populations, this region was sequenced in 122 isolates from six different geographic areas. A Bayesian method was applied to test for the action of natural selection under a population genetic model that incorporates recombination. The analysis was integrated with a structural model of PvDBP(II), and T-and B-cell epitopes were localized on the 3-D structure. Results: The results suggest that: (i) recombination plays an important role in determining the haplotype structure of PvDBP(II), and (ii) PvDBP(II) appears to contain neutrally evolving codons as well as codons evolving under natural selection. Diversifying selection preferentially acts on sites identified as epitopes, particularly on amino acid residues 417, 419, and 424, which show strong linkage disequilibrium. Conclusions: This study shows that some polymorphisms of PvDBP(II) are present near the erythrocyte-binding domain and might serve to elude antibodies that inhibit cell invasion. Therefore, these polymorphisms should be taken into account when designing vaccines aimed at eliciting antibodies to inhibit erythrocyte invasion.

Design of 1D and 2D molecule-based magnets with the ligand 4,5-dimethyl-1,2-phenylenebis(oxamato)

Three new bimetallic oxamato-based magnets with the proligand 4,5-dimethyl-1,2-phenylenebis-(oxamato) (dmopba) were synthesized using water or dimethylsulfoxide (DMSO) as solvents. Single crystal X-ray diffraction provided structures for two of them: [MnCu(dmopba)(H(2)O)(3)]n center dot 4nH(2)O (1) and [MnCu(dmopba)(DMSO)(3)](n center dot)nDMSO (2). The crystalline structures for both 1 and 2 consist of linearly ordered oxamato-bridged Mn(II)Cu(II) bimetallic chains. The magnetic characterization revealed a typical behaviour of ferrimagnetic chains for 1 and 2. Least-squares fits of the experimental magnetic data performed in the 300-20 K temperature range led to J(MnCu) = -27.9 cm(-1), g(Cu) = 2.09 and g(Mn) = 1.98 for 1 and J(MnCu) = -30.5 cm(-1), g(Cu) = 2.09 and g(Mn) = 2.02 for 2 (H = -J(MnCu)Sigma S(Mn, i)(S(Cu, i) + S(Cu, i-1))). The two-dimensional ferrimagnetic system [Me(4)N](2n){Co(2)[Cu(dmopba)](3)}center dot 4nDMSO center dot nH(2)O (3) was prepared by reaction of Co(II) ions and an excess of [Cu(dmopba)](2-) in DMSO. The study of the temperature dependence of the magnetic susceptibility as well as the temperature and field dependences of the magnetization revealed a cluster glass-like behaviour for 3.

Ligand Reduces Galectin-1 Sensitivity to Oxidative Inactivation by Enhancing Dimer Formation

Galectin-1 (Gal-1) regulates leukocyte turnover by inducing the cell surface exposure of phosphatidylserine (PS), a ligand that targets cells for phagocytic removal, in the absence of apoptosis. Gal-1 monomer- dimer equilibrium appears to modulate Gal-1-induced PS exposure, although the mechanism underlying this regulation remains unclear. Here we show that monomer- dimer equilibrium regulates Gal-1 sensitivity to oxidation. A mutant form of Gal-1, containing C2S and V5D mutations (mGal-1), exhibits impaired dimerization and fails to induce cell surface PS exposure while retaining the ability to recognize carbohydrates and signal Ca(2+) flux in leukocytes. mGal-1 also displayed enhanced sensitivity to oxidation, whereas ligand, which partially protected Gal-1 from oxidation, enhanced Gal-1 dimerization. Continual incubation of leukocytes with Gal-1 resulted in gradual oxidative inactivation with concomitant loss of cell surface PS, whereas rapid oxidation prevented mGal-1 from inducing PS exposure. Stabilization of Gal-1 or mGal-1 with iodoacetamide fully protected Gal-1 and mGal-1 from oxidation. Alkylation-induced stabilization allowed Gal-1 to signal sustained PS exposure in leukocytes and mGal-1 to signal both Ca(2+) flux and PS exposure. Taken together, these results demonstrate that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidative inactivation and provides a mechanism whereby ligand partially protects Gal-1 from oxidation.

Calcium is essential for the structural integrity of the cysteine-rich, ligand-binding repeat of the low-density lipoprotein receptor

Seven cysteine-rich repeats form the ligand-binding region of the low-density lipoprotein (LDL) receptor. Each of these repeats is assumed to bind a calcium ion, which is needed for association of the receptor with its ligands, LDL and beta-VLDL. The effects of metal ions on the folding of the reduced N-terminal cysteine-rich repeat have been examined by using reverse-phase high-performance liquid chromatography to follow the formation of fully oxidized isomers with different disulfide connectivities. in the absence of calcium many of the 15 possible isomers formed on oxidation, whereas in its presence the predominant product at equilibrium had the native disulfide bond connectivities. Other metals were far less effective at directing disulfide bond formation: Mn2+ partly mimicked the action of Ca2+, but Ba2+, Sr2+, and Mg2+ had little effect. This metal-ion specificity was also observed in two-dimensional H-1 NMR spectral studies: only Ca2+ induced the native three-dimensional fold. The two paramagnetic ions, Gd3+ and Mn2+, and Cd2+ did not promote adoption of a well-defined structure, and the two paramagnetic ions did not displace calcium ions. The location of calcium ion binding sites in the repeat was also explored by NMR spectroscopy. The absence of chemical shift changes for the side chain proton resonances of Asp26, Asp36, and Glu37 from pH 3.9 to 6.8 in the presence of calcium ions and their proximal location in the NMR structures implicated these side chains as calcium ligands. Deuterium exchange NMR experiments also revealed a network of hydrogen bonds that stabilizes the putative calcium-binding loop.

Folding, calcium binding, and structural characterization of a concatemer of the first and second ligand-binding modules of the low-density lipoprotein receptor

The ligand-binding domain of the low-density lipoprotein (LDL) receptor is comprised of seven tandemly repeated ligand-binding modules, each being approximately 40 amino acids long and containing six conserved cysteine residues. We have expressed and characterized a concatemer of the first two modules (LB1 and LB2) of the human LDL receptor. Oxidative folding of the recombinant concatemer (rLB(1-2)), in the presence of calcium ions, gave a single dominant isomer with six disulfide bonds. Peptic cleavage of the short Linker region that connects the last cysteine residue of LB1 and the first cysteine residue of LB2 yielded two discrete fragments, thus excluding the presence of intermodule disulfide bonds. The N-terminal module, LB1, reacted with a conformation-specific monoclonal antibody (IgG-C7) made to LB1 in the native LDL receptor. From this, we concluded that the first module was correctly folded, with the same set of disulfide bonds as LB1 of the LDL receptor. The disulfide bond connections of LB2 were identified from mass spectral analysis of fragments formed by digestion of the C-terminal peptic fragment with elastase. These data showed that the disulfide bonds of LB2 connected Cys(I) and Cys(III), Cys(II) and Cys(V), and Cys(IV) and Cys(VI). This pattern is identical to that found for recombinant LB1 and LB2. The concatemer has two high-affinity calcium-binding sites, one per module. An analysis of the secondary chemical shifts of C alpha protons shows that the conformations of LB1 and LB2 in the concatemer are very similar to those of the individual modules, with no evidence for strong interactions between the two modules.

Relation of TNF-related apoptosis-inducing ligand (TRAIL) receptor and FLICE-inhibitory protein expression to TRAIL-induced apoptosis of melanoma

Past studies have shown that apoptosis mediated by TNF-related apoptosis-inducing ligand (TRAIL) is regulated by the expression of two death receptors [TRAIL receptor 1 (TRAIL-RI) and TRAIL-R2] and two decoy receptors (TRAIL-R3 and TRAIL-R4) that inhibit apoptosis, In previous studies, me have shown that TRAIL but not other members of the tumor necrosis factor family induce apoptosis in approximately two-thirds of melanoma cell lines. Here, we examined whether the expression of TRAIL-R at the mRNA and protein level in a panel of 28 melanoma cell lines and melanocytes correlated with their sensitivity to TRAIL-induced apoptosis, We report that at least three factors appear to underlie the variability in TRAIL-induced apoptosis. (a) Pour of nine cell lines that were insensitive to TRAIL-induced apoptosis failed to express death receptors, and in two instances, lines were devoid of all TRAIL-Rs. Southern analysis suggested this was due to loss of the genes for the death receptors, (b) Despite the presence of mRNA for the TRAIL-R, some of the lines failed to express TRAIL-R protein on their surface. This was evident for TRAIL-RI and more so for the TRAIL decoy receptors TRAIL-R3 and -R4, Studies on permeabilized cells revealed that the receptors were located within the cytoplasm and redistribution from the cytoplasm may represent a posttranslational control mechanism. (c) Surface expression of TRAIL-RI and -R2 (but not TRAIL-R3 and -R4) showed an overall correlation with TRAIL-induced apoptosis. However, certain melanoma cell lines and clones were relatively resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and moderate levels of TRAIL-RI and -R2 expression. This may indicate the presence of inhibitors within the cells, but resistance to apoptosis could not be correlated with expression of the caspase inhibitor FLICE-inhibitory protein. mRNA for another TRAIL receptor, osteoprotegerin, was expressed in 22 of the melanoma lines but not on melanocytes. Its role in induction of apoptosis remains to be studied. These results appear to have important implications for future clinical studies on TRAIL.

Metal-centred versus ligand-centred luminescence quenching of a macrocyclic copper(II) complex

The new macrocyclic ligand trans-6-(9-anthracenylmethylamino)-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecan-13-amine has been synthesized and characterised as its copper(II) complex and the crystal structure of this complex has been determined. Fluorescence of the anthracenyl group of the macrocycle is quenched in its free base form and when complexed with Cu-II. Fluorescence returns when Lewis acids such as H+ and Zn-II are added to solutions of the ligand, indicating that photoinduced electron transfer from the amine lone pairs is responsible for fluorescence quenching in the free base form. By contrast, fluorescence of the complex is quenched by intramolecular electronic energy transfer.