Mixed ligand palladium(II) and platinum(II) complexes of tertiary diphosphines and benz-1,3-imidazoline-2-thione,benz-1,3-oxazoline-2-thione or benz-1,3-thiazoline-2-thione

Palladium(II) and platinum(II) complexes containing the mixed ligands tertiary diphosphines Ph₂P(CH₂) _n PPh₂, (n = 1–4) and benz-1,3-imidazoline-2-thione, benz-1,3-oxazoline-2-thione or benz-1,3-thiazoline-2-thione have been prepared and characterized by elemental analysis, magnetic susceptibility, molar conductance and i.r. spectral data. ³¹P–{¹H}-n.m.r. data have been applied to characterize the produced linkage isomers.     

R7-binding protein targets the G protein β5/R7-regulator of G protein signaling complex to lipid rafts in neuronal cells and brain

Background  

Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins), composed of Gα, Gβ, and Gγ subunits, are positioned at the inner face of the plasma membrane and relay signals from activated G protein-coupled cell surface receptors to various signaling pathways. Gβ5 is the most structurally divergent Gβ isoform and forms tight heterodimers with regulator of G protein signalling (RGS) proteins of the R7 subfamily (R7-RGS). The subcellular localization of Gβ 5/R7-RGS protein complexes is regulated by the palmitoylation status of the associated R7-binding protein (R7BP), a recently discovered SNARE-like protein. We investigate here whether R7BP controls the targeting of Gβ5/R7-RGS complexes to lipid rafts, cholesterol-rich membrane microdomains where conventional heterotrimeric G proteins and some effector proteins are concentrated in neurons and brain.     

{\rtf1\ansi\ansicpg1250\deff0\deflang1038\deflangfe1038\deftab708{\fonttbl{\f0\froman\fprq2\fcharset238{\*\fname Times New Roman;}Times New Roman CE;}} \viewkind4\uc1\pard\f0\fs20 Processing of non-isothermal TG data \par }

Decomposition of dichlorodifluoromethane in thermal plasma was investigated theoretically by computing the equilibrium composition of the gas mixtures involving carbon, chlorine and fluorine in presence of argon (which is assumed to be the main plasma gas) and/or in addition of hydrogen and calcium together with hydrogen. The calculations were carried out for the temperature range between 500 and 6000 K and for the total pressure of the system of 1 bar. Use is made of the fact that a thermal plasma is a plasma in (local) thermal equilibrium, which makes possible the theoretical determination of its equilibrium composition at definite temperature by employing Gibbs free energy data for the compounds present in the system and assuming that the equilibrium of the system corresponds to its minimum energy state. The results of calculations show that toxic molecules and radicals can be, under convenient conditions (appropriate temperature and amount of added substances), converted into stable non-toxic species like CaF₂ and CaCl₂.     

Adducts of niobium(V) and tantalum(V) halides. XIV. Structure and relative stability of the adducts with some phosphoryl compounds

The adducts of niobium(V) and tantalum(V) halides with some phosphoryl compounds have been studied in chloroform solution by ¹H- and ¹⁹F-FT-NMR. spectroscopy. These octahedral adducts of general formula MX₅ · L (M = Nb, Ta; X = F, Cl, Br; L = phosphoryl ligand) are monomeric and neutral. Their relative stability constants have been determined at ?60°. The stabilities are controlled by electronic effects of substituents on the phosphoryl group.     

Polymerization-induced phase separation in polyether-sulfone modified epoxy resin systems: effect of curing reaction mechanism

Polyethersulfone (PES)-modified epoxy systems with stepwise reaction were studied throughout the entire curing process by using optical microscopes, time-resolved light scattering (TRLS), and a rheolometry instrument compared with that of chainwise polymerization. The results suggested that the phase separation process is mainly controlled by the diffusion of epoxy oligomers for stepwise mechanism system and by that of epoxy monomers for chainwise mechanism system. In case of high PES content (SPES-20%) light-scattering results showed a viscoelastic phase separation and the characteristic relaxation time of phase separation can be described well by the WLF equation. However, in the case of low PES content (SPES-14%) secondary phase separation phenomenon was observed by Optical Microscope and further demonstrated by rheological study.     

Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries

Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three building blocks are coupled sequentially in efficient alkylation reactions that eliminate the need for product purification. We demonstrate the power of the approach by combinatorially reacting 15 bromoacetamide-activated tripeptides, 42 amines, and 6 bis-electrophile cyclization linkers to generate a 3780-compound library with minimal effort. Screening against thrombin yielded a potent and selective inhibitor (K_i = 4.2 ± 0.8 nM) that efficiently blocked blood coagulation in human plasma. Structure–activity relationship and X-ray crystallography analysis revealed that two of the three building blocks acted synergistically and underscored the importance of combinatorial screening in macrocycle development. The three-component library synthesis approach is general and offers a promising avenue to generate macrocycle ligands to other targets.

Combination of three efficient chemical reactions allows for solution-phase synthesis of 3780 macrocycles and identification of potent thrombin inhibitor.     

A general approach toward the synthesis of C-nucleoside pyrazolo[1,5-a]-1,3,5-triazines and their 3',5'-bisphosphate C-nucleotide analogues as the first reported in vivo stable P2Y(1)-receptor antagonists

In our effort to identify potent purinergic P2Y(1) receptor antagonists as potent platelet aggregation inhibitors with enhanced metabolic stability, we developed an efficient route for the large-scale preparation of 2'-deoxy-C-nucleosides of pyrazolo[1,5-a]-1,3,5-triazine. The key strategic elements of this novel synthetic approach involved the following: (i) the use of a novel activating group, the N-methyl-N-phenylamino group, which was easily generated in high yield by treatment of the pyrazolo[1,5-a]-1,3,5-triazin-4-one (5) with phosphorus oxychloride and dimethylaniline under high pressure, (ii) a regio- and stereospecific palladium-mediated coupling reaction of the readily available unprotected glycal 1,4-anhydro-2-deoxy-D-erythro-pent-1-enitol (4b) and the 8-iodo derivative (16), and (iii) the stereoselective reduction of the ketone group of the furanosyl ring followed by the subsequent displacement of the N-methyl-N-phenylamino group upon treatment with methylamine. The beta configuration at the anomeric C-1' position of the glycal moieties was perfectly retained throughout this conversion. This procedure afforded 8-(2'-deoxy-beta-D-ribofuranosyl)-2-methyl-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (21) and 8-(2'-deoxy-beta-D-xylofuranosyl)-2-methyl-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (24) with an overall yield of 50% and 39%, respectively. Finally, the conversion of nucleosides 21 and 24 to the pyrazolotriazine C-nucleotides 3',5'-bisphosphate 2 and 3',5'-cyclophosphate 26 is also described herein and represents the first reported nucleotide derivatives within the pyrazolo[1,5-a]-1,3,5-triazine series. Preliminary biological testing has shown that compound 2 strongly inhibits ADP-induced human platelet aggregation and shape change and possesses significant efficacies 30 min after injection in rat, highlighting a strong P2Y(1)-receptor antagonist activity in vitro combined with a prolonged duration of action in vivo.     

A DFT study of pyramidalized alkenes: 7-oxasesquinorbornenes and 7,7′-dioxasesquinorbornenes

  DFT calculations of 7′–oxasesquinorbornenes and 7,7′-dioxasesquinorbornenes using the B3LYP/6–31G* method are reported. All the investigated structures (syn- and anti- derivatives) showed significant non-planarity of the central double bond, with the exception of those anti-derivatives possessing symmetrical structures. The influence of the replacement of the methylene groups at position 7- of the norbornene fragment with oxygen and the introduction of second and third (peripheral) double bonds and benzene rings on the molecular and electronic structures of these molecules have also been investigated. Received: 11 November 2002 / Accepted: 6 June 2002 / Published online: 29 April 2003     

Synthesis of 2•,3•-Dideoxy-3•-<Emphasis Type="Italic">C</Emphasis>-hydroxymethylcytidine Phosphonomethyl Derivatives

Phosphonomethyl substituted 2?,3?-Dideoxy-3?-C-hydroxymethylcytidines have been synthesized and evaluated for their anti HIV-1 activities. The sugar moiety was synthesized starting from (S)-5-hydroxymethylfuran-2-(5H)-one using photocatalyzed addition of methanol. Reduction of the lactone, condensation with silylated 4-methoxy-2(1H)pyrimidinone, followed by phosphonomethylation and deprotection gave the title compounds. The compounds were tested for inhibition of HIV-1 activity but did not show any significant antiviral activity.     

Synthesis,crystal structure and luminescent property of a novel H<Subscript>2</Subscript>O-bridged cobalt(II) polymer with one-dimensional chain structure

The coordination compound [Co(C₁₀H₇COO)₂(H₂O)₃]_2n · 4nH₂O was prepared by the reaction of 1-naphthoic acid and cobalt(II) acetate tetrahydrate in basic solution, and was fully characterized by X-ray diffraction, element analysis, FTIR, TG-DTA and luminescent spectra. In the crystal the six-coordinated Co(II) centers are linked into one-dimensional zigzag chains by water molecules, which are further assembled into a two-dimensional network through weak inter-chain C–H···π interactions. The solid complex exhibits favorable fluorescent properties similar to those of free ligand at room temperature, which can be assigned to the intraligand electronic transfer.