Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Tests of the CBM Rich readout and Daq prototype

The CBM RICH detector is an integral component of the future CBM experiment at FAIR, providing efficient electron identification and pion suppression necessary for the measurement of rare dileptonic probes in heavy ion collisions. An overview of the CBM RICH readout and DAQ system prototype is given, consisting of the PADIWA preamplifier-discriminator board, the TDC-HUB board TRBv3, and DAQ and analysis code in the CbmRoot framework. The laboratory setup built for studying the timing characteristics of the readout chain and the analysis results obtained using the laboratory measurements are presented. The fine time calibration and inter-channel delay correction techniques and their implementation and effect are discussed.     

Nitrostyrene Derivatives of Adenosine 5′-Glutarates as Selective Inhibitors of the Epidermal Growth Factor Receptor Protein Tyrosine Kinase

The syntheses and biological activities of some nitrostyrene derivatives of adenosine 5′-glutarates, a novel class of selective, bi-substrate-type inhibitors of the EGF receptor protein tyrosine kinase with IC₅₀ values around 1 μM . Only marginal inhibition of the tyrosine kinases v-able and c-src and of the serine/threonine kinase PKC was observed. Compounds 8, 9, 11 , and 12 – lacking the adenosine moiety – were ten times less active than the most potent derivatives, whereas 17 – lacking the nitrostyryl part – showed no inhibitory activity at all. Most of the compounds showed potent antiproliferative activity against an EGF-dependent mouse keratinocyte cell line.     

Synthesis of Modified Tripeptides and Tetrapeptides as potential bisubstrate inhibitors of the epidermal growth factor receptor protein tyrosine kinase

The synthesis of a series of bisubstrate inhibitors of the epidermal growth factor receptor protein kinase (EGF-R PTK) consisting of small pep tides linked covalently to adenosine via appropriate triphosphate substitutes is described. Boc-Glu(O^tBu)-Tyr-Leu-OBzl ( 5 ) and Ac-Glu(O^tBu)-Tyr-Leu-Arg(Pmc)-NH₂ ( 8 ; Pmc = 2,2,5,7,8-pentamethylchroman-6-sulfonyl) were prepared by standard peptide chemistry, (Scheme 1), then modified at the OH group of tyrosine either with adipic anhydride or with 4-(chlorosulfonyl)benzoic acid, 4-(chlorosulfonyl)-2-hydroxybenzoic acid, or benzene-1,4-disulfonyldichloride (Scheme 2), and finally coupled with the 5′-OH group of 2′,3′-O-isopropylideneadenosine (Scheme 3). In addition, N⁶-[(benzyloxy)carbonyl]-2′,3′-O-isopropylidene-adenosine 5′-(hydrogenhexanedioate) ( 26 ), an ATP substitute, was coupled with the morpholide of 5 (Scheme 4). Removal of the protecting groups gave the bisubstrate analogs 23, 24 , and 28. The compounds synthesized were tested as inhibitors of the EGF-R PTK. The most active bisubstrate-type inhibitor was 24 , composed of the tripeptide sequence H-Glu-Tyr-Leu-OBzl, the 2-hydroxy-4-sulfonylbenzoyl moiety, and adenosine; it showed an IC₅₀ value of 33 μM.     

Structure of the antibiotic Roridin E

Structure 1 has been established for roridin E (C₂₉H₃₈O₈), an antibiotic isolated from cultures of Myrothecium species. Base catalysed hydrolysis of 1 gave the known sesquiterpene alcohol verrucarol ( 4 ; C₁₅H₂₂O₄) and 2′-anhydrororidinic acid ( 6 ; C₁₄H₂₀O₆), a new dicarboxylic acid. The structure of 6 was determined by spectral analysis of its dimethyl ester 7 , dimethyl hexahydro-2′-anhydrororidinate ( 9 ), the acetyl derivative 10 , and the oxidation product 11 .     

A Thiazole-linked Covalent Organic Framework for Lithium-Sulphur Batteries

Lithium-sulphur (Li−S) batteries are a promising alternative power source, as they can provide a higher energy density than current lithium-ion batteries. Porous materials are often used as cathode materials as they can act as a host for sulphur in such batteries. Recently, covalent organic frameworks (COFs) have also been used, however they typically suffer from stability issues, resulting in limited and thus insufficient durability under practical conditions and applications. Herein, we report the synthesis of a crystalline and porous imine-linked triazine-based dimethoxybenzo-dithiophene functionalized COF (TTT-DMTD) incorporating high-density redox sites. The imine linkages were further post-synthetically transformed to yield a robust thiazole-linked COF (THZ-DMTD) by utilizing a sulphur-assisted chemical conversion method, while maintaining the crystallinity. As a synergistic effect of its high crystallinity, porosity and the presence of redox-active moieties, the thiazole-linked THZ-DMTD exhibited a high capacity and long-term stability (642 mAh g⁻¹ at 1.0 C; 78.9 % capacity retention after 200 cycles) when applied as a cathode material in a Li−S battery.     

A study of some parameters relevant to the response of harwell PMMA dosimeters to gamma and electron irradiation

The effects on the radiation response of Harwell polymethylmethacrylate (PMMA) dosimeters of dose-rate, radiation type, temperature during irradiation and post-irradiation storage, and post-irradiation stability, are of importance to the operators of commercial irradiation facilities.

This paper describes recent studies of the effects of some of these parameters on the radiation response of Harwell Red 4034, Amber 3042, and Gammachrome YR Perspex dosimeters, and provides data on batch to batch variation and shelf-life.