Shedding Light on the Interactions of Hydrocarbon Ester Substituents upon Formation of Dimeric Titanium(IV) Triscatecholates in DMSO Solution

The dissociation of hierarchically formed dimeric triple lithium bridged triscatecholate titanium(IV) helicates with hydrocarbyl esters as side groups is systematically investigated in DMSO. Primary alkyl, alkenyl, alkynyl as well as benzyl esters are studied in order to minimize steric effects close to the helicate core. The ¹H NMR dimerization constants for the monomer–dimer equilibrium show some solvent dependent influence of the side chains on the dimer stability. In the dimer, the ability of the hydrocarbyl ester groups to aggregate minimizes their contacts with the solvent molecules. Due to this, most solvophobic alkyl groups show the highest dimerization tendency followed by alkenyls, alkynyls and finally benzyls. Furthermore, trends within the different groups of compounds can be observed. For example, the dimer is destabilized by internal double or triple bonds due to π–π repulsion. A strong indication for solvent supported London dispersion interaction between the ester side groups is found by observation of an even/odd alternation of dimerization constants within the series of n-alkyls, n-Ω-alkenyls or n-Ω-alkynyls. This corresponds to the interaction of the parent hydrocarbons, as documented by an even/odd melting point alternation.     

How Ligand Binding Affects the Dynamical Transition Temperature in Proteins

The biochemical functions of proteins are activated at the protein glass transition temperature, which has been proposed to be dependent upon protein-water interactions. However, at the molecular level it is unclear how ligand binding to well-defined binding sites can influence this transition temperature. We thus report molecular dynamics (MD) simulations of the ϵ subunit from thermophilic Bacillus PS3 in the ATP-free and ligand-bound states over a range of temperatures from 20 to 300 K, to study the influence of ligand association upon the transition temperature. We also measure the protein mean square displacement (MSD) in each state, which is well established as a means to quantify this dynamical temperature dependence. We find that the transition temperature is largely unaffected by ligand association, but the MSD beyond the transition temperature increases more rapidly in the ATP-free state. Our data suggests that ligands can effectively “shield” a binding site from solvent, and hence stabilize protein domains with increasing temperature.     

Metabolism of Deuterated erythro‐Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones

Epoxides of fatty acids are hydrolyzed by epoxide hydrolases (EHs) into dihydroxy fatty acids which are of particular interest in the mammalian leukotriene pathway. In the present report, the analysis of the configuration of dihydroxy fatty acids via their respective hydroxylactones is described. In addition, the biotransformation of (±)‐erythro‐7,8‐ and ‐3,4‐dihydroxy fatty acids in the yeast Saccharomyces cerevisiae was characterized by GC/EI‐MS analysis. Biotransformation of chemically synthesized (±)‐erythro‐7,8‐dihydroxy(7,8‐²H₂)tetradecanoic acid ((±)‐erythro‐ 1 ) in the yeast S. cerevisiae resulted in the formation of 5,6‐dihydroxy(5,6‐²H₂)dodecanoic acid ( 6 ), which was lactonized into (5S,6R)‐6‐hydroxy(5,6‐²H₂)dodecano‐5‐lactone ((5S,6R)‐ 4 ) with 86% ee and into erythro‐5‐hydroxy(5,6‐²H₂)dodecano‐6‐lactone (erythro‐ 8 ). Additionally, the α‐ketols 7‐hydroxy‐8‐oxo(7‐²H₁)tetradecanoic acid ( 9a ) and 8‐hydroxy‐7‐oxo(8‐²H₁)tetradecanoic acid ( 9b ) were detected as intermediates. Further metabolism of 6 led to 3,4‐dihydroxy(3,4‐²H₂)decanoic acid ( 2 ) which was lactonized into 3‐hydroxy(3,4‐²H₂)decano‐4‐lactone ( 5 ) with (3R,4S)‐ 5 =88% ee. Chemical synthesis and incubation of (±)‐erythro‐3,4‐dihydroxy(3,4‐²H₂)decanoic acid ((±)‐erythro‐ 2 ) in yeast led to (3S,4R)‐ 5 with 10% ee. No decano‐4‐lactone was formed from the precursors 1 or 2 by yeast. The enantiomers (3S,4R)‐ and (3R,4S)‐3,4‐dihydroxy(3‐²H₁)nonanoic acid ((3S,4R)‐ and (3R,4S)‐ 3 ) were chemically synthesized and comparably degraded by yeast without formation of nonano‐4‐lactone. The major products of the transformation of (3S,4R)‐ and (3R,4S)‐ 3 were (3S,4R)‐ and (3R,4S)‐3‐hydroxy(3‐²H₁)nonano‐4‐lactones ((3S,4R)‐ and (3R,4S)‐ 7 ), respectively. The enantiomers of the hydroxylactones 4, 5 , and 7 were chemically synthesized and their GC‐elution sequence on Lipodex^® E chiral phase was determined.     

Nanoparticles positioning effect on properties of (PS-PANI/NiNPs) nanocomposite films

This work presents the effect of driven nickel nanoparticles (NiNPs) towards the surface of (PS-PANI)/NiNPs nanocomposite upon the application of a uniform magnetic field. The purpose is to obtain distinguishable optoelectronic and electrical properties. This process increases the surface roughness and its reactivity, and enables the tuning of the optical and electrical properties. Based on the results from X-ray photoelectron and Fourier-transform infrared spectroscopies, the magnetically-driven NiNPs to the surface are oxidized, forming NiONPs and NiOHNPs. This oxidation effect transforms the surface from a hydrophilic to a hydrophobic state. In addition, the optical bandgap energy decreases from 4.04 to 3.77 eV, and the electrical conductivity increases from 12.77 μS/cm to 57.80 μS/cm and 77.52 μS/cm, for 50 and 100 mT magnetic fields, respectively, which is attributed to the well-dispersed magnetic nanoparticles in the PS-PANI polymer matrix, resulting in a high homogeneous nanocomposite film.     

Vibrational Predissociation Spectra of C2N− and C3N−: Bending and Stretching Vibrations

We present infrared predissociation spectra of C₂N⁻(H₂) and C ₃N⁻(H₂) in the 300–1850 cm⁻¹ range. Measurements were performed using the FELion cryogenic ion trap end user station at the Free Electron Lasers for Infrared eXperiments (FELIX) laboratory. For C₂N⁻(H₂), we detected the CCN bending and CC−N stretching vibrations. For the C₃N⁻(H₂) system, we detected the CCN bending, the CC−CN stretching, and multiple overtones and/or combination bands. The assignment and interpretation of the presented experimental spectra is validated by calculations of anharmonic spectra within the vibrational configuration interaction (VCI) approach, based on potential energy surfaces calculated at explicitly correlated coupled cluster theory (CCSD(T)-F12/cc-pVTZ−F12). The H₂ tag acts as an innocent spectator, not significantly affecting the C_2,3N⁻ bending and stretching mode positions. The recorded infrared predissociation spectra can thus be used as a proxy for the vibrational spectra of the bare anions.     

Response of the jalpaite membrane copper(II) ion-selective electrode in marine waters

The response of the Orion 94-29 Cu^II ion-selective electrode (ISE) [employing a jalpaite membrane] in seawater has been related to levels of free Cu^II yielding results for the Derwent River and San Diego Bay that are 2 to 3 orders of magnitude higher than those for the Pacific Ocean. Response data for the electrode in acidified seawater at pH 2 are internally consistent with total Cu^II levels determined using differential pulse anodic stripping voltammetry (DPASV) and graphite furnace atomic absorption spectrometry (GFAAS). It has been found that, even in acidified seawater, the organic ligands influence the response of the electrode, and this effect can be compensated successfully by either analyzing UV-photooxidized seawater and/or using a standard addition technique. The assigned ISE results for total Cu^II in acidified seawater fall within ± (0.1–0.5) pCu unit of values determined using GFAAS. Electrode drift in seawater can be minimized by using a polished electrode that has been conditioned in seawater for 24 h. The improved response rate of a conditioned ISE minimizes electrode soaking times and sample contamination through membrane corrosion.     

Conductivity studies of aqueous solutions of stereoisomers of tartaric acids and tartrates. Part II: D-, L-, andmeso-tartaric acids

Conductivity measurements on aqueous solutions of D-tartaric acid, L-tartaric acid, andmeso-tartaric acid were performed in the temperature range 278.15–308.15 K. The equivalent limiting conductivity of the bitartrate anion, λ°(HTar^-), is evaluated with regard to the primary and secondary steps of dissociation of the acids in aqueous solutions by use of the Quint and Viallard equation for unsymmetrical electrolytes.     

Nature-inspired dimerization as a strategy to modulate neuropeptide pharmacology exemplified with vasopressin and oxytocin

Vasopressin (VP) and oxytocin (OT) are cyclic neuropeptides that regulate fundamental physiological functions via four G protein-coupled receptors, V_1aR, V_1bR, V₂R, and OTR. Ligand development remains challenging for these receptors due to complex structure–activity relationships. Here, we investigated dimerization as a strategy for developing ligands with novel pharmacology. We regioselectively synthesised and systematically studied parallel, antiparallel and N- to C-terminal cyclized homo- and heterodimer constructs of VP, OT and dVDAVP (1-deamino-4-valine-8-d-arginine-VP). All disulfide-linked dimers, except for the head-to-tail cyclized constructs, retained nanomolar potency despite the structural implications of dimerization. Our results support a single chain interaction for receptor activation. Dimer orientation had little impact on activity, except for the dVDAVP homodimers, where an antagonist to agonist switch was observed at the V_1aR. This study provides novel insights into the structural requirements of VP/OT receptor activation and spotlights dimerization as a strategy to modulate pharmacology, a concept also frequently observed in nature.

Structural and pharmacological study of parallel, antiparallel and N- to C-terminal cyclized homo- and heterodimers of vasopressin and oxytocin. This study spotlights dimerization as a strategy to modulate the pharmacology of neuropeptides.     

Synthesis and single-crystal X-ray diffraction studies of 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide and certain related nucleosides

1-β-D-Ribofuranosyl- 21 , 1-(2-deoxy-β-D-erytftro-pento fur anosyl)- 27 and 1-β-D-arabinofuranosyl- 29 derivatives of 1,2,4-triazole-3-sulfonamide ( 19 ) have been prepared. Glycosylation of the silylated 19 with 1,2,3,5-tetra-0-acetyl-β-D-ribofuranose ( 5 ) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleoside ( 20 ), which on ammonolysis afforded 1-β-D-ribofuranosyl-1,2,4-triazole-3-sulfonamide ( 21 ). Stereospecific glycosylation of the sodium salt of 19 with either 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 22 ) or 1-chloro-2,3,5-tri-0-benzyl-α-D-arabinofuranose ( 23 ) provided the corresponding protected nucleosides 26 and 28. Deprotection of 26 and 28 furnished 1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,4-triazole-3-sulfonamide ( 27 ) and 1-β-D-arabinofuranosyl-1,2,4-triazole-3-sulfonamide ( 29 ), respectively. 2-0-D-Ribofuranosyl-1,2,4-triazole-3(4H)-thione ( 7 ) and 4-β-D-ribofuranosyl-1,2,4-triazole-3(2H)-thione ( 9 ) were also prepared utilizing either an acid catalyzed fusion of 1,2,4-triazole-3(1H,2H)-thione ( 4 ) with 5 , the reaction of 5 with silylated 4 in the presence of trimethylsilyl triflate, or by ring closure of 4-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)thiosemicarbazide ( 10 ) with mixed anhydride and subsequent deacylation. The synthesis of 1-β-D-ribofuranosyl-3-benzylthio-1,2,4-triazole ( 15 ) has also been accomplished by the silylation procedure employing 3-benzylthio-1,2,4-triazole ( 13 ) and 5 to give 1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)-3-benzylthio-1,2,4-triazole ( 14 ). Deacetylation of 14 furnished 15 . The structural assignments of 7, 14 and 21 were made by single-crystal X-ray diffraction analysis and their hydrogen bonding characteristics have been studied. The sulfonamido-1,2,4-triazole nucleosides are devoid of any significant antiviral or antitumor activity in cell culture.     

Cure of epoxy resins with cyanoacetamides

Cyanoacetamides are a novel class of curing agents for epoxy resins. Since reaction products of epoxy compounds with cyanoacetamides have not yet been described, we investigated the reaction of phenyl-glycidylether (PGE) and N-isobutylcyanoacetamide (NICA) under the conditions of the epoxy cure (120–150°C). Twenty-two fractions of the reaction product have been separated by preparative TLC and characterized by FD and MS mass spectroscopy. The structures of 10 reaction product have been elucidated by MS, NMR, and IR techniques. They belong to the classes of cyclic urethanes, spiro-dilactones, cyclo-oxa-1-hepten-4-one-2, pyrimidones, aminocrotononitrile, and tertiary amine. This complex model reaction mixture does not enable us to propose a curing mechanism. However practical cure of Bisphenol A diglycidylether (BADGE) yields clear and tough solids with a glass transition temperature up to 200°C, good mechanical strength, and high adhesion to metal surface. Cyanoacetamides are latent hardeners requiring a curing initiator. Since N-4-chlorophenyl-N′-dimethylurea is a latent initiator, liquid, homogeneous, storage stable “one shot” systems can be formulated which harden quickly above 120°C. Heat aging properties of cured specimens are reported. A series of novel liquid, resinous, and crystalline cyanoacetamides and their potential as curing agent are described.