Dissociative Recombination of Protonated Formic Acid: Implications for Molecular Cloud and Cometary Chemistry

At the heavy ion storage ring CRYRING in Stockholm, Sweden, we have investigated the dissociative recombination of DCOOD2+ at low relative kinetic energies, from ~1 meV to 1 eV. The thermal rate coefficient has been found to follow the expression k(T) = 8.43 × 10-7 (T/300)^-0.78 cm3 s-1 for electron temperatures, T, ranging from ~10 to ~1000 K. The branching fractions of the reaction have been studied at ~2 meV relative kinetic energy. It has been found that ~87% of the reactions involve breaking a bond between heavy atoms. In only 13% of the reactions do the heavy atoms remain in the same product fragment. This puts limits on the gas-phase production of formic acid, observed in both molecular clouds and cometary comae. Using the experimental results in chemical models of the dark cloud, TMC-1, and using the latest release of the UMIST Database for Astrochemistry improves the agreement with observations for the abundance of formic acid. Our results also strengthen the assumption that formic acid is a component of cometary ices.

Rare-earth quinolinates: Infrared-emitting molecular materials with a rich structural chemistry

Near-infrared-emitting rare-earth chelates based on 8-hydroxyquinoline have appeared frequently in recent literature, because they are promising candidates for active components in near-infrared-luminescent optical devices, such as optical amplifiers, organic light-emitting diodes, .... Unfortunately, the absence of a full structural investigation of these rare-earth quinolinates is hampering the further development of rare-earth quinolinate based materials, because the luminescence output cannot be related to the structural properties. After an elaborate structural elucidation of the rare-earth quinolinate chemistry we can conclude that basically three types of structures can be formed, depending on the reaction conditions: tris complexes, corresponding to a 1:3 metal-to-ligand ratio, tetrakis complexes, corresponding to a 1:4 metal-to-ligand ratio, and trimeric complexes, with a 3:8 metal-to-ligand ratio. The intensity of the emitted near-infrared luminescence of the erbium(Ill) complexes is highest for the tetrakis complexes of the dihalogenated 8-hydroxyquinolinates.

Studies on acyl pyrrolidine inhibitors of HCV RNA-dependent RNA polymerase to identify a molecule with replicon antiviral activity

The SAR development is described for a series of N-acyl pyrrolidine inhibitors of the Hepatitis C virus RNA-dependent RNA polymerase, NS5B, from tractable Delta 21 enzyme inhibitors to an example with antiviral activity in a cellular assay (HCV replicon). (c) 2007 Elsevier Ltd. All rights reserved.

5-aryl-pyrazolo[3,4-b]pyridazines: Potent inhibitors of glycogen synthase kinase-3 (GSK-3)

Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography. (C) 2003 Elsevier Science Ltd. All rights reserved.

3-anilino-4-arylmaleimides: Potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3)

Potent 3-anilino-4-arylmaleimide glycogen synthase kinase-3 (GSK-3) inhibitors have been prepared using automated array methodology. A number of these are highly selective, having little inhibitory potency against more than 20 other protein kinases. (C) 2001 Elsevier Science Ltd. All rights reserved.

Non-thiazolidinedione antihyperglycaemic agents. Part 3: The effects of stereochemistry on the potency of alpha-methoxy-beta-phenylpropanoic acids.

Rhizopus delemar lipase catalyzed ester hydrolysis of the alpha-methoxy-beta-phenylpropanoate (I) affords the (R)-(+) and (S)-(-) isomers in > 84% enantiomeric excess. Abs. stereochem. was detd. by a single crystal X-ray anal. of a related synthetic analog. The activity of these two enantiomers on glucose transport in vitro and as anti-diabetic agents in vivo is reported and their unexpected equivalence attributed to an enzyme-mediated stereospecific isomerization of the (R)-(+) isomer. Binding studies using recombinant human PPAR-gamma (peroxisomal proliferator activated receptor gamma), now established as a mol. target for this compd. class, indicate a 20-fold higher binding affinity for the (S) antipode relative to the (R) antipode.

The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives.

Aryl hydroxylamine derivs. have been synthesized that are some of the most potent inhibitors of hCMV protease prepd. to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to inhibit via formation of a sulfinanilide at Cys138.

Non-thiazolidinedione antihyperglycemic agents. 2: alpha-Carbon substituted-beta-phenylpropanoic acids.

Buckle, D. R.; Cantello, B. C. C.; Cawthorne, M. A.; Coyle, P. J.; Dean, D. K.; Faller, A.; Haigh, D.; Hindley, R. M.; Lefcott, L. J.; et al. Dep. Medicinal Chem., Smithkline Beecham Pharmaceuticals, Surrey, UK. Bioorganic & Medicinal Chemistry Letters (1996), 6(17), 2127-2130. Publisher: Elsevier, CODEN: BMCLE8 ISSN: 0960-894X. Journal written in English. CAN 125:238227 AN 1996:573179 CAPLUS (Copyright (C) 2009 ACS on SciFinder (R)) Abstract The thiazolidine-2,4-dione ring of insulin-sensitizing antidiabetic agents can be replaced by ?-acyl-, ?-alkyl- and ?-(aralkyl)-carboxylic acids. The inclusion of an addnl. lipophilic moiety affords compds., equipotent to BRL 48482.

Non-thiazolidinedione antihyperglycemic agents. 1: Alpha-Heteroatom substituted-beta-phenylpropanoic acids.

A review with 22 refs. The 5-benzylthiazolidine-2,4-dione moiety of insulin sensitizing antidiabetic agents can be replaced by a range of ?-heteroatom functionalized ?-phenylpropanoic acids. ?-Oxy-carboxylic acids show potent antidiabetic activity and one compd., the ?-ethoxyacid (SB 213068), is one of the most potent antihyperglycemic agents yet reported.

The synthesis of BRL 49653 - a novel and potent antihyperglycemic agent.

Modifications based upon a metabolite of ciglitazone afforded BRL 49653 (I), a novel potent insulin sensitizer. A facile synthesis of this compd. is described.

Fast, copper-free click chemistry: a convenient solid-phase approach to oligonucleotide conjugation

Solid-phase oligonucleotide conjugation by nitrile oxide-alkyne click cycloaddition chemistry has been successfully demonstrated; the reaction, compatible with all nucleobases, requires no metal catalyst and proceeds under physiological conditions.