Molecular structures of 3-hydroxybenzoic acid and 4-hydroxybenzoic acid, obtained by gas-phase electron diffraction and theoretical calculations

The structures of 3-hydroxybenzoic acid and 4-hydroxybenzoic acid have been determined by gas-phase electron diffraction using results from quantum chemical calculations to inform the choice of restraints applied to some of the structural parameters. The results from the study presented here demonstrate that resonance hybrids are not as helpful in rationalizing the structures of 2-, 3-, and 4-hydroxybenzoic acids as are models based upon electrostatic effects.

Amyloid-like fibrillogenesis through supramolecular helix-mediated self-assembly of tetrapeptides containing non-coded alpha-aminoisobutyric acid (Aib) and 3-aminobenzoic acid (m-ABA)

Single-crystal X-ray diffraction studies of two terminally protected tetrapeptides Boc-Ile-Aib-Val-m-ABA-OMe (I) and Boc-Ile-Aib-Phe-m-ABA-OMe (II) (Aib = alpha-aminoisobutyric acid; m-ABA = meta-aminobenzoic acid) reveal that they form continuous H-bonded helices through the association of double-bend (type III and I) building blocks. NMR Studies support the existence of the double-bend (type Ill and I) structures of the peptides in solution also. Field emission scanning electron-microscopic (FE-SEM) and high-resolution transmission electron-microscopic (HR-TEM) images of the peptides exhibit amyloid-like fibrils in the solid state. The Congo red-stained fibrils of peptide I and II, observed between crossed polarizers, show green-gold birefringence, a characteristic of amyloid fibrils.

Moderate fish-oil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians

Background: The mechanisms involved in the increased mortality from coronary artery disease in British Indo-Asians are not well understood. Objectives: This study aimed to investigate whether British Indo-Asian Sikhs have higher plasma triacylglycerol concentrations, lower platelet phospholipid levels, and lower dietary intakes of long-chain n-3 polyunsaturated fatty acids (PUFAs) than do age- and weight-matched Europeans and whether moderate dietary fish-oil intake can reverse these differences. Design: A randomized, double-blind, placebo-controlled, parallel, fish-oil intervention study was performed. After a 2-wk run-in period, 44 Europeans and 40 Indo-Asian Sikhs were randomly assigned to receive either 4.0 g fish oil [1.5 g eicosapentaenoic acid (EPA) and 1.0 g docosahexaenoic acid (DHA)] or 4.0 g olive oil (control) daily for 12 wk. Results: At baseline, the Indo-Asians had significantly higher plasma triacylglycerol, small dense LDL, apolipoprotein B, and dietary and platelet phospholipid n-6 PUFA values and significantly lower long-chain n-3 PUFAs (EPA and DHA) than did the Europeans. A significant decrease in plasma triacylglycerol, plasma apolipoprotein B-48, and platelet phospholipid arachidonic acid concentrations and a significant increase in plasma HDL concentrations and platelet phospholipid EPA and DHA levels were observed after fish-oil supplementation. No significant effect of ethnicity on the responses to fish-oil supplementation was observed. Conclusions: Moderate fish-oil supplementation contributes to a reversal of lipid abnormalities and low n-3 PUFA levels in Indo-Asians and should be considered as an important, yet simple, dietary manipulation to reduce CAD risk in Indo-Asians with an atherogenic lipoprotein phenotype.

Redox- and glucose-responsive hydrogels from poly(vinyl alcohol) and 4-mercaptophenylboronic acid

Novel redox- and glucose-responsive hydrogels have been synthesized by simple mixing of poly(vinyl alcohol) (PVA) and 4-mercaptophenylboronic acid (MPBA) in aqueous solutions (pH > 9) in an oxidative aqueous media. These hydrogels are produced through the formation of disulfide linkages between MPBA molecules in an oxidative environment (oxygen dissolved in solution or hydrogen peroxide added to the reaction mixture) and complexation via dynamic covalent bonds between PVA and MPBA dimer. These hydrogels show degradation in solutions of l-glutathione and d-glucose.

Double coupling reactions of 3,4-bis(stannyl)furanone: facile preparation of diaryl- and dibenzylfuranones

The palladium-catalyzed cross-coupling reaction of 3,4-bis(tributylstannyl)furan-2(5H)-one using chelating ligand or polar solvent gives mixtures of single and double coupled products, even when one equivalent of halide coupling partner is used. After optimization, the double coupling reaction was shown to be general, with the use of two equivalents of aryl iodides giving 3,4-disubstituted furanones, The reaction using benzyl bromides proceeds at lower temperatures than the corresponding coupling using aryl iodides, giving dibenzylfuranones. The methodology has been exemplified in a synthesis of (+/-)-hinokinin.

Synthesis of chiral 3,4,5,6-tetrahydro-1,4-thiazin-2-ones (thiamorpholin-2-ones)-novel heterocycles possessing enhanced carbonyl electrophilicity over their oxygen counterparts

We report herein the first synthesis of chiral derivatives possessing the 1,4-thiazinone core. As predicted, the thiolactone is more susceptible to nucleophilic attack than the equivalent lactone system.

m-aminobenzoic acid inserted beta-turn in acyclic tripeptides: a peptidomimetic design

X-ray diffraction studies show that peptides Boc-Leu-Aib-m-ABA-OMe (I) (Aib, alpha-aminoisobutyric acid; m-ABA, meta-aminobenzoic acid) and Boc-Phe-Aib-m-ABA-OMe, (II) adopt a type-II beta-turn conformation, solely stabilized by co-operative steric interactions amongst the amino acid residues. This type of U-turn without any intramolecular hydrogen bonding is generally referred to as an open turn. Although there are some examples of constrained cyclic peptides in which o-substituted benzenes have been inserted to mimic the turn region of the neurotrophin, a nerve growth factor, peptides I and II present novel two examples where m-aminobenzoic acid has been incorporated in the beta-turn of acyclic tripeptides. The result also demonstrates the first crystallographic evidence of a beta-turn structure containing an inserted m-aminobenzoic acid, which can be considered as a rigid gamma-aminobutyric acid with an all-trans extended configuration. (c) 2005 Elsevier Ltd. All rights reserved.

3-and 3,4-substituted pyrroles and thiophenes and their corresponding polymers: a review

In the field of conducting polymers, both poly(pyrrole) and poly(thiophene) have been investigated extensively and are used currently in a wide variety of applications including microelectronics, electrode materials, sensors and optoelectronics. Amongst these polymers, 3- and 3,4- substituted poly(pyrroles) and poly(thiophenes) have received significant attention in recent years as demonstrated by the increase in the number of patents and publications that describe their use. This review covers the development in the synthesis of 3- and 3,4- Substituted poly(pyrroles) and poly(thiophenes) over the last 30 years, their polymerisation in addition to describing the material properties and applications of the resulting polymers. In particular, this review focuses upon the variety of methodologies employed for the synthesis of 3- and 3,4-substituted pyrroles and thiophenes as well as upon the broad range of functional groups that can be attached to the heterocyclic ring system in order to tailor the properties of the resulting polymers.

Inhibition of cellular proliferation by the genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone is mediated by DNA damage and activation of the ATR signalling pathway

The cellular actions of genistein, and its in vivo metabolites, are believed to mediate the decreased risk of breast cancer associated with high soy consumption. The genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone (THIF), induced G2-M cell cycle arrest in T47D tumorigenic breast epithelial cells via a mechanism involving the activation of ataxia telangiectasia and Rad3-related kinase (ATR) via its phosphorylation at Ser(428). This activation of ATR appeared to result from THIF-induced increases in intracellular oxidative stress, a depletion of cellular GSH and an increase in DNA strand breakage. THIF treatment also led to an inhibition of cdc2, which was accompanied by the phosphorylation of both p53 (Ser(15)) and Chk1 (Ser(296)) and the de-activation of cdc25C phosphatase. We suggest the anti-proliferative actions of THIF may be mediated by initial oxidative DNA damage, activation of ATR and downstream regulation of the p53 and Chk1 pathways leading to cell cycle arrest in G2-M. This may represent one mechanism by which genistein exerts its cellular activity in vivo. (c) 2007 Elsevier Inc. All rights reserved.

The intracellular genistein metabolite 5,7,3 ',4 '-tetrahydroxyisoflavone mediates G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling pathway

The cellular actions of genistein are believed to mediate the decreased risk of breast cancer associated with high soy consumption. We have investigated the intracellular metabolism of genistein in T47D tumorigenic and MCF-10A nontumorigenic cells and assessed the cellular actions of resultant metabolites. Genistein selectively induced growth arrest and G2-M phase cell cycle block in T47D but not MCF10A breast epithelial cells. These antiproliferative effects were paralleled by significant differences in the association of genistein to cells and in particular its intracellular metabolism. Genistein was selectively taken up into T47D cells and was subject to metabolism by CYP450 enzymes leading to the formation of both 5,7,3',4'-tetrahydroxyisoflavone (THIF) and two glutathionyl conjugates of THIF THIF inhibited cdc2 activation via the phosphorylation of p38 MAP kinase, suggesting that this species may mediate genistein's cellular actions. THIF exposure activated p38 and caused subsequent inhibition of cyclin B1 (Ser 147) and cdc2 (Thr 161) phosphorylation, two events critical for the correct functioning of the cdc2-cyclin B1 complex. We suggest that the formation of THIF may mediate the cellular actions of genistein in tumorigenic breast epithelial cells via the activation of signaling through p38. (c) 2006 Elsevier Inc. All rights reserved.

Assessment of long chain n-3 polyunsaturated fatty acid status and clinical outcome in adults receiving home parenteral nutrition

Background & aims: Long term parenteral nutrition rarely supplies the long chain n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA). The aim of this study was to assess long chain n-3 PUFA status in patients receiving home parenteral. nutrition (HPN). Methods: Plasma phospholipid fatty acids were measured in 64 adult HPN patients and compared with 54 age, sex and BMI matched controls. Logistic regression analysis was used to identify factors related to plasma fatty acid fractions in the HPN patients, and to identify factors associated with the risk of clinical. complications. Results: Plasma phospholipid fractions of EPA, DPA and DHA were significantly tower in patients receiving HPN. Factors independently associated with tow fractions included high parenteral energy provision, tow parenteral lipid intake, tow BMI and prolonged duration of HPN. Long chain n-3 PUFA fractions were not associated with incidence of either central venous catheter associated infection or central venous thrombosis. However, the fraction of EPA were inversely associated with plasma alkaline phosphatase concentrations. Conclusions: This study demonstrates abnormal long chain n-3 PUFA profiles in patients receiving HPN. Reduced fatty acid intake may be partly responsible. Fatty acid metabolism may also be altered. (C) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.