22 research outputs found
Synthesis of 5-azaindoles via a cycloaddition reaction between nitriles and donor-acceptor cyclopropanes.
A new method for the synthesis of 5-azaindole derivatives is reported. A [3+2] dipolar cycloaddition between nitriles and a 3,4-cyclopropanopiperidine followed by SeO(2) oxidation affords the target compounds in moderate to excellent yields. The divergent nature and cost effectiveness of this method makes it very suitable for combinatorial applications in the pharmaceutical industry
An optimised synthesis of high performance radiation-grafted anion-exchange membranes
High performance benzyltrimethylammonium-type alkaline anion-exchange membranes (AEM), for application in electrochemical devices such as anion-exchange membrane fuel cells (AEMFC), were prepared by the radiation grafting (RG) of vinylbenzyl chloride (VBC) onto 25 ÎŒm thick poly(ethylene-co-tetrafluoroethylene) (ETFE) films followed by amination with trimethylamine. Reductions in the electron-beam absorbed dose and amount of expensive, potentially hazardous VBC were achieved by using water as a diluent (reduced to 30â40 kGy absorbed dose and 5 vol% VBC) instead of the prior state-of-the-art method that used organic propan-2-ol diluent (required 70 kGy dose and 20 vol% VBC monomer). Furthermore, the water from the aqueous grafting mixture was easily separated from the residual monomer (after cooling) and was reused for a further grafting reaction: the resulting AEM exhibited an ion-exchange capacity of 2.1 mmol gâ1 (cf. 2.1 mmol gâ1 for the AEM made using a fresh grafting mixture). The lower irradiation doses resulted in mechanically stronger RG-AEMs compared to the reference RG-AEM synthesised using the prior state-of-the-art method. A further positive off-shoot of the optimisation process was the discovery that using water as a diluent resulted in an enhanced (i.e. more uniform) distribution of VBC grafts as proven by Raman microscopy and corroborated using EDX analysis: this led to enhancement in the Clâ anion-conductivities (up to 68 mS cmâ1 at 80 °C for the optimised fully hydrated RG-AEMs vs. 48 mS cmâ1 for the prior state-of-the-art RG-AEM reference). A down-selected RG-AEM with an ion-exchange capacity = 2.0 mmol gâ1, that was synthesised using the new greener protocol with a 30 kGy electron-beam absorbed dose, led to an exceptional beginning-of-life H2/O2 AEMFC peak power density of 1.16 W cmâ2 at 60 °C in a benchmark test using industrial standard Pt-based electrocatalysts and unpressurised gas supplies: this was higher than the 0.91 W cmâ1 obtained with the reference RG-AEM (IEC = 1.8 mmol gâ1) synthesised using the prior state-of-the-art protocol
Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization
We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2
An Optimised Synthesis of High Performance Radiation-Grafted Anion-Exchange Membranes
High performance benzyltrimethylammonium-type alkaline anion-exchange membranes (AEM), for application in electrochemical devices such as anion-exchange membrane fuel cells (AEMFC), were prepared by the radiation grafting (RG) of vinylbenzyl chloride (VBC) onto 25 ÎŒm thick poly(ethylene-co-tetrafluoroethylene) (ETFE) films followed by amination with trimethylamine. Reductions in the electron-beam absorbed dose and amount of expensive, potentially hazardous VBC were achieved by using water as a diluent (reduced to 30â40 kGy absorbed dose and 5 vol% VBC) instead of the prior state-of-the-art method that used organic propan-2-ol diluent (required 70 kGy dose and 20 vol% VBC monomer). Furthermore, the water from the aqueous grafting mixture was easily separated from the residual monomer (after cooling) and was reused for a further grafting reaction: the resulting AEM exhibited an ion-exchange capacity of 2.1 mmol gâ1 (cf. 2.1 mmol gâ1 for the AEM made using a fresh grafting mixture). The lower irradiation doses resulted in mechanically stronger RG-AEMs compared to the reference RG-AEM synthesised using the prior state-of-the-art method. A further positive off-shoot of the optimisation process was the discovery that using water as a diluent resulted in an enhanced (i.e. more uniform) distribution of VBC grafts as proven by Raman microscopy and corroborated using EDX analysis: this led to enhancement in the Clâ anion-conductivities (up to 68 mS cmâ1 at 80 °C for the optimised fully hydrated RG-AEMs vs. 48 mS cmâ1 for the prior state-of-the-art RG-AEM reference). A down-selected RG-AEM with an ion-exchange capacity = 2.0 mmol gâ1, that was synthesised using the new greener protocol with a 30 kGy electron-beam absorbed dose, led to an exceptional beginning-of-life H2/O2 AEMFC peak power density of 1.16 W cmâ2 at 60 °C in a benchmark test using industrial standard Pt-based electrocatalysts and unpressurised gas supplies: this was higher than the 0.91 W cmâ1obtained with the reference RG-AEM (IEC = 1.8 mmol gâ1) synthesised using the prior state-of-the-art protocol