Electron Paramagnetic Resonance for the Detection of Electrochemically Generated Hydroxyl Radicals: Issues Associated with Electrochemical Oxidation of the Spin Trap.

For the detection of electrochemically produced hydroxyl radicals (HO) from the oxidation of water on a boron-doped diamond (BDD) electrode, electron paramagnetic resonance spectroscopy (EPR) in combination with spin trap labels is a popular technique. Here, we show that quantification of the concentration of HO from water oxidation via spin trap electrochemical (EC)-EPR is problematic. This is primarily due to the spin trap oxidizing at potentials less positive than water, resulting in the same spin trap-OH adduct as formed from the solution reaction of OH with the spin trap.

Metallohelices that kill Gram-negative pathogens using intracellular antimicrobial peptide pathways.

A range of new water-compatible optically pure metallohelices - made by self-assembly of simple non-peptidic organic components around Fe ions - exhibit similar architecture to some natural cationic antimicrobial peptides (CAMPs) and are found to have high, structure-dependent activity against bacteria, including clinically problematic Gram-negative pathogens. A key compound is shown to freely enter rapidly dividing cells without significant membrane disruption, and localise in distinct foci near the poles. Several related observations of CAMP-like mechanisms are made biophysical measurements, whole genome sequencing of tolerance mutants and transcriptomic analysis.

Electrocardiographic characteristics in patients with heart failure and normal ejection fraction: A systematic review and meta-analysis.

Background: Little is known about ECG abnormalities in patients with heart failure and normal ejection fraction (HeFNEF) and how they relate to different etiologies or outcomes.

Methods And Results: We searched the literature for peer-reviewed studies describing ECG abnormalities in HeFNEF other than heart rhythm alone. Thirty five studies were identified and 32,006 participants.

NMR-based assignment of isoleucine vs. allo-isoleucine stereochemistry.

A simple H and C NMR spectrometric analysis is demonstrated that permits differentiation of isoleucine and allo-isoleucine residues by inspection of the chemical shift and coupling constants of the signals associated with the proton and carbon at the α-stereocentre. This is applied to the estimation of epimerisation during metal-free N-arylation and peptide coupling reactions.

Antifreeze Protein Mimetic Metallohelices with Potent Ice Recrystallization Inhibition Activity.

Antifreeze proteins are produced by extremophile species to control ice formation and growth, and they have potential applications in many fields. There are few examples of synthetic materials which can reproduce their potent ice recrystallization inhibition property. We report that self-assembled enantiomerically pure, amphipathic metallohelicies inhibited ice growth at just 20 μM.

Chronic total occlusion in an infarct-related coronary artery and the risk of appropriate ICD therapies.

Introduction: Risk stratification for ventricular arrhythmias in patients with ischemic cardiomyopathy needs to be improved. Coronary chronic total occlusions in an infarct-related artery (IRA-CTOs) have been associated with an increased arrhythmic risk. This study aimed to evaluate the association between IRA-CTOs and appropriate implantable cardioverter-defibrillator (ICD) therapies.

Synthesis and characterization of triangulene.

Triangulene, the smallest triplet-ground-state polybenzenoid (also known as Clar's hydrocarbon), has been an enigmatic molecule ever since its existence was first hypothesized. Despite containing an even number of carbons (22, in six fused benzene rings), it is not possible to draw Kekulé-style resonant structures for the whole molecule: any attempt results in two unpaired valence electrons. Synthesis and characterization of unsubstituted triangulene has not been achieved because of its extreme reactivity, although the addition of substituents has allowed the stabilization and synthesis of the triangulene core and verification of the triplet ground state via electron paramagnetic resonance measurements.

Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions.

The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG(⧧) rotation varied between <8.0 and 31.0 kcal mol(-1)).

Are Some Anticoagulants More Equal Than Others? - Evaluating the Role of Novel Oral Anticoagulants in AF Ablation.

Left atrial ablation strategies are being increasingly performed as a Class 1 therapeutic indication for drug refractory paroxysmal atrial fibrillation (AF). Traditionally AF ablation has been performed with patients on uninterrupted warfarin therapy, however over the last few years, novel oral anticoagulants (NOACs) have emerged as attractive alternatives to warfarin in order to reduce stroke risk due to AF. NOACs are therefore increasingly being used instead of warfarin in the management of AF.

Correction: Unique post-translational oxime formation in the biosynthesis of the azolemycin complex of novel ribosomal peptides from sp. FXJ1.264.

[This corrects the article DOI: 10.1039/C5SC03021H.].

Unique post-translational oxime formation in the biosynthesis of the azolemycin complex of novel ribosomal peptides from sp. FXJ1.264.

Streptomycetes are a rich source of bioactive specialized metabolites, including several examples of the rapidly growing class of ribosomally-biosynthesized and post-translationally-modified peptide (RiPP) natural products. Here we report the discovery from sp. FXJ1.

Total synthesis of the azolemycins.

The first total syntheses of newly isolated polyazole natural products azolemycins A-D, along with the synthesis of the tetra-oxazole non-natural analogue, are described.

Stereo- and Chemodivergent NHC-Promoted Functionalisation of Arylalkylketenes with Chloral.

Stereo- and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N-heterocyclic carbenes, giving selectively either β-lactones (up to 88:12 dr, up to 94 % ee) or α-chloroesters (up to 94 % ee). Either 2-arylsubstitution or an α-branched iPr alkyl substituent within the ketene favours the chlorination pathway, allowing chloral to be used as an electrophilic chlorinating reagent in asymmetric catalysis.

Ring closing metathesis reactions of α-methylene-β-lactams: application to the synthesis of a simplified phyllostictine analogue with herbicidal activity.

Ring closing metathesis (RCM) reactions of α-methylene-β-lactams are used to construct strained 11- and 12-membered macrocycles that mimic key structural elements of phyllostictine A. The highest yield and stereoselectivity was achieved making 12-membered macrocycle Z-19 with use of a p-methoxyphenyl group on the lactam nitrogen. Interestingly, substrate concentration had an important influence on the stereochemical course of the reaction.

Photo-induced living radical polymerization of acrylates utilizing a discrete copper(II)-formate complex.

A photo-polymerization protocol, utilizing a pre-formed and well-characterized Cu(II) formate complex, [Cu(Me6-Tren)(O2CH)](ClO4), mediated by UV light is described. In the absence of additional reducing agents and/or photosensitizers, ppm concentrations of the oxidatively stable [Cu(Me6-Tren)(O2CH)](ClO4), furnish near-quantitative conversions within 2 h, yielding poly(acrylates) with low dispersities (∼1.10) and exceptional end-group fidelity, capable of undergoing in situ chain extension and block copolymerization.

Synthesis of 1- and 4-substituted piperazin-2-ones via Jocic-type reactions with N-substituted diamines.

Enantiomerically-enriched trichloromethyl-containing alcohols, obtained by asymmetric reduction, can be transformed regioselectively into 1-substituted piperazinones by modified Jocic reactions with little or no loss of stereochemical integrity. This methodology can be easily used to synthesise important pharmaceutical compounds such as the fluorobenzyl intermediate of a known PGGTase-I inhibitor.

The synthesis and STM/AFM imaging of 'olympicene' benzo[cd]pyrenes.

H-Benzo[cd]pyrene ('Olympicene') is a polyaromatic hydrocarbon and non-Kekulé fragment of graphene. A new synthetic method has been developed for the formation of 6H-benzo[cd]pyrene and related ketones including the first time isolation of the unstable alcohol 6H-benzo[cd]pyren-6-ol. Molecular imaging of the reaction products with scanning tunnelling microscopy (STM) and non-contact atomic force microscopy (NC-AFM) characterised the 6H-benzo[cd]pyrene as well as the previously intangible and significantly less stable 5H-benzo[cd]pyrene, the fully conjugated benzo[cd]pyrenyl radical and the ketones as oxidation products.

How does Chronic Atrial Fibrillation Influence Mortality in the Modern Treatment Era?

Atrial fibrillation (AF) continues to impose a significant burden upon healthcare resources. A sustained increase in the ageing population and better survival from conditions such as ischaemic heart disease have ensured that both the incidence and prevalence of AF continue to increase significantly. AF can lead to complications such as embolism and heart failure and these acting in concert with its associated co-morbidities portend increased mortality risk.

Asymmetric triplex metallohelices with high and selective activity against cancer cells.

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens.

Trichloromethyl ketones: asymmetric transfer hydrogenation and subsequent Jocic-type reactions with amines.

Amino-amides are important pharmaceutical building-blocks. The enantioselective reduction of trichloromethyl ketones using ruthenium transfer hydrogenation catalysts is reported. The products react in a range of Jocic-type reactions to give enantiomerically enriched amino-amides.

New developments in cardiac resynchronization therapy.

Cardiac resynchronization therapy significantly reduces mortality and morbidity in patients with heart failure and ventricular dyssynchrony. This is a dynamic field with some exciting recent advances, and these future directions are discussed in this review.

Iron/tetramethylethylenediamine-catalyzed ambient-temperature coupling of alkyl Grignard reagents and aryl chlorides.

Tetramethylethylenediamine (TMEDA) acts as cheap and readily removed ligand in the iron-catalyzed coupling of alkyl Grignard reagents and activated aryl chlorides. The use of TMEDA allows for low ligand and iron catalyst loading as well as an increased reaction concentration and an ambient reaction temperature on a mole scale.

Oxidation of tertiary amine-derivatized surfaces to control protein adhesion.

Selective oxidation of ω-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM.