The synthesis and characterization of three propynyloxycoumarins are reported in this work together with the formation of three different series of gold(i) organometallic complexes. Neutral complexes are constituted by water soluble phosphines (PTA and DAPTA) which confer water solubility to them. The X-ray crystal structure of 7-(prop-2-in-1-yloxy)-1-benzopyran-2-one and its corresponding dialkynyl complex is also shown and the formation of rectangular dimers for the gold derivative in the solid state can be observed. A detailed analysis of the absorption and emission spectra of both ligands and complexes allows us to attribute the luminescent behaviour to the coumarin organic ligand. Moreover, the presence of the gold(i) metal atom seems to be responsible for an increase of coumarin phosphorescence emission. The biological activity of the complexes showed that the anionic complexes triggered strong cytotoxic effects in two different cell lines whereas the neutral gold alkynyl complexes led to lower effects against tumor cell growth. Thioredoxin reductase (TrxR) inhibition was very strong in the case of the neutral complexes (IC50 values below 0.1 μM) but moderate for the anionic complexes (IC50 values above 0.8 μM).

A phosphine-gold(i)-alkynyl-coumarin complex, [Au{7-(prop-2-ine-1-yloxy)-1-benzopyran-2-one}(DAPTA)] (), was synthesized and the formation of long luminescent fibers in solution was characterized via fluorescence microscopy and dynamic light scattering. The fibers presented strong blue and green luminescence, suggesting that the gold(i) in the complex increased intersystem crossing due to the heavy atom effect, resulting in a significant increase in triplet emission. The X-ray structure of the fibers indicates that both aurophilic, π-π interactions and hydrogen bonding contribute to their formation in aqueous solvents.

The first dendrimers containing P-stereogenic monophosphines as peripheral groups were obtained by reacting the protected BH3-LiCH2PPhR (R = 2-biphenylyl, 9-phenanthryl) with zeroth- and first-generation chlorocarbosilane dendrimers, followed by treatment with morpholine and subsequent chromatographic purification. The first-generation dendrimer with the 9-phenanthryl-substituted phosphine could not be obtained, due to the incomplete functionalization of all the arms of the dendrimer. The reaction of the chiral dendrimers with the dinuclear allyl complex [Pd(μ-Cl)(η3-2-MeC3H4)]2 allowed us to graft PdCl(η3-2-MeC3H4) units on their surface. Complete characterization of these species was achieved by multinuclear NMR spectra (including 2D experiments), mass spectrometry, and optical rotation determinations. The catalytic properties of the new palladodendrimers were tested in the asymmetric hydrovinylation of styrene. To evaluate possible dendritic effects, two model chiral compounds, (CH3)3SiCH2PPhR, were prepared. The results in terms of activity, selectivity, and enantiomeric excess depend strongly on the nature of the phosphine and the halide abstractor. The best results were achieved with the employment of the first-generation dendrimer containing the 2-biphenylyl-substituted phosphine and NaBARF (79% ee toward the S enantiomer). In all experiments, the major enantiomer of 3-phenyl-1-butene had the absolute configuration S, with the exception of that catalyzed by the 9-phenanthryl-substituted phosphine dendrimer, which afforded (R)-3-phenyl-1-butene as the predominant enantiomer.

Two new monoanionic PNP pincer type ligands have been synthesized, the achiral 3,6-di-tert-butyl-1,8-bis((diphenyl-phosphino)methyl)-9H-carbazole CbzdiphosH (5) and the chiral 3,6-di-tert-butyl-1,8-bis(((2R,5R)-2,5-diphenylphospholan-1-yl)methyl)-9H-carbazole CbzdipholH (7), both of which were initially prepared as their borane complexes. The synthesis of CbzdiphosH is based on the reaction between the key intermediate 1,8-bis(bromomethyl)-3,6-di-tert-butyl-9H-carbazole (3) and lithium diphenylphosphide-borane complex. The chiral ligand CbzdipholH was prepared by treating 3 with lithium (2R,5R)-2,5-diphenylphospholanide-borane complex and subsequent deprotection with diethylamine. The complexation of the two ligands with nickel, palladium and rhodium was investigated, for which the conformational behavior of the ligands was found to be different. Although the arrangement of the donor atoms in all crystallographically characterized complexes is approximately square planar, the carbazole plane in Cbzdiphos complexes is inclined relative to the coordination plane. On the other hand, a helical twist is observed in Cbzdiphol complexes.

A series of chiral mono-, di-, and trinuclear gold(I) complexes have been prepared and used as precatalysts in the asymmetric cyclohydroamination of N-protected γ-allenyl sulfonamides. The stereodirecting ligands were mono-, di-, and tridentate 2,5-diphenylphospholanes, which possessed C(1), C(2), and C(3) symmetry, respectively, thereby rendering the catalytic sites in the di- and trinuclear complexes symmetry equivalent. The C(3)-symmetric trinuclear complex displayed the highest activity and enantioselectivity (up to 95 % ee), whilst its mono- and dinuclear counterparts exhibited considerably lower enantioselectivities and activities. A similar trend was observed in a series of mono-, di-, and trinuclear 2,5-dimethylphospholane gold(I) complexes. Aurophilic interactions were established from the solid-state structures of the trinuclear gold(I) complexes, thereby raising the question as to whether these secondary forces were responsible for the different catalytic behavior observed.

Abstract-Recent loss-of-function studies highlight the importance of the transcription factor GATA4 in the myocardial response to injury in the adult heart. However, the potential effects of gain-in-function of GATA4 overexpression, and transcription factors in general, is hindered by the fact that transcription factors are neither secreted nor taken up by cells. Key Words: GATA4 Ⅲ myocardial infarct Ⅲ cell-based gene therapy Ⅲ VP22 Ⅲ intercellular delivery of protein G ATA4 is critical for the viability and hypertrophic response of cardiac myocytes following myocardial injury. 1,2 Consistent with these findings, GATA4 has been shown to directly induce the expression of BCL2 in cardiac myocytes in vitro. 3 These findings suggest that the local overexpression of GATA4 could lead to local cardiac hypertrophy and improved cardiac myocyte survival. The goal of this study was to assess, for the first time, the effects of local GATA4 overexpression in the infarct border zone at a time remote from myocardial infarction in a model of ischemic cardiomyopathy. To do so, because transcription factors are neither secreted nor internalized by surrounding cells, we used a novel method of local GATA4 delivery to the infarct border zone.We achieved local GATA4 delivery by combining cellbased gene therapy with a cell-penetrating protein (CPP). Cell-based gene therapy has been shown to be an effective strategy for stimulating angiogenesis and improving heart function. 4 -6 Moreover CPPs, by serving as vectors for the transmembrane intercellular delivery of fused proteins, have emerged as a tool to modulate biological activities. 7-11 Cardiac fibroblasts were engineered in culture to overexpress a chimeric protein encoding GATA4 and the CPP VP22. We recently demonstrated the utility of this strategy to deliver the nonsecreted marker protein green fluorescent protein (GFP) to myocardial tissue. 12 In this previous study, we demonstrated that VP22 chimeric proteins are delivered to Ϸ1 mm 2 of myocardium in a direction radial to the needle track. In the present study, we quantified the effects of sustained GATA4:VP22 release into the infarct border zone in a rat model of ischemic cardiomyopathy induced by left anterior descending (LAD) ligation 1 month before cell delivery. We aim to show that the cell-based sustained delivery of nonsecreted functional proteins offers a potential novel strategy to study the effects of nonsecreted proteins in adult hearts at a time remote from myocardial injury, as well as a potentially interesting strategy for the optimization of cardiac function following myocardial injury.

The complexes [Au(4-pyridylethynyl)(phosph)] (phosph = PTA (1), DAPTA (2)) are known to produce supramolecular aggregates and gels in water. We studied the impact of these aggregation processes in the absorption spectra, (1)H NMR (at different temperatures and concentrations), and DLS and estimated the equilibrium constant for a single step aggregation of the molecule (K = 26760 and 2590 M(-1) for 1 and 2, respectively, at 25 °C). We present spectroscopic evidence for the presence of Au···Au contacts in the aggregates: the recorded changes on (1)H NMR and the appearance of new absorption bands assigned to (σ*Au···Au-π*) have been attributed to the short (Au···Au) average distances in the aggregates. Relativistic density functional theory computations support the existence of short Au···Au distances and reveal charge-transfer in the aurophilic interactions. The free energy for a single step aggregation was calculated from the experimental data, and the value obtained (ΔG ∼ -20 kJ/mol) is in good agreement with the expected values in the order of the energies found for hydrogen bonds. The DFT computations confirm the experimental findings that aggregation of monomer 1 is stronger than the aggregation of monomer 2 and the existence of aurophilic interactions.

Experimental results on Ziegler‐Natta catalysts, based on observations made with the electron microscope, and a qualitative comparison of the stereospecificity of various catalyst combinations are given. The polymerization of olefin in these experiments is performed in the gas phase on dry catalysts in the absence of solvent or excess aluminium alkyl. The crystallographic structure of the lateral faces of α‐TiCl3 is established by electron microscopy and electron diffraction. The electron micrographs of α‐TiCl3–AlMe3 catalysts show that the active centers, which are revealed by the dotwise formation of polymer, are located along the growth spirals, on lateral faces, and on surface defects. These regions of the surface are the only regions in which the surface titanium atoms are incompletely coordinated. The presence of chlorine vacancies and exposed titanium atoms is therefore an essential condition for the formation of active centers. However, the number of active centers is small in comparison to the number of incompletely coordinated titanium atoms, and hence it is concluded that the normally occurring α‐TiCl3 sites with one vacancy do not yield active centers on reaction with aluminum alkyl. It is proposed that the reaction with aluminum alkyl on such sites leads ultimately to a bimetallic complex which fills the original vacancy on the titanium atom. That the complexation is reversible and that the deblocked alkylated site, which is of the type proposed by Cossee, is an active center is not excluded. Such a center would, however, give atactic polymer. Similar complex formation on a TiCl3 site having originally two vacancies would leave one vacancy on the titanium atom. This is believed to be the center of stereospecific polymerization. A model of this active center and a mechanism of polymer growth on it are proposed.