Lithium storage mechanisms in purpurin based organic lithium ion battery electrodes

Current lithium batteries operate on inorganic insertion compounds to power a diverse range of applications, but recently there is a surging demand to develop environmentally friendly green electrode materials. To develop sustainable and eco-friendly lithium ion batteries, we report reversible lithium ion storage properties of a naturally occurring and abundant organic compound purpurin, which is non-toxic and derived from the plant madder. The carbonyl/hydroxyl groups present in purpurin molecules act as redox centers and reacts electrochemically with Li-ions during the charge/discharge process. The mechanism of lithiation of purpurin is fully elucidated using NMR, UV and FTIR spectral studies. The formation of the most favored six membered binding core of lithium ion with carbonyl groups of purpurin and hydroxyl groups at C-1 and C-4 positions respectively facilitated lithiation process, whereas hydroxyl group at C-2 position remains unaltered

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

Inferior frontal sulcal hyperintensities on brain MRI are associated with amyloid positivity beyond Age—results from the multicentre observational DELCODE study

Inferior frontal sulcal hyperintensities (IFSHs) on fluid-attenuated inversion recovery (FLAIR) sequences have been proposed to be indicative of glymphatic dysfunction. Replication studies in large and diverse samples are nonetheless needed to confirm them as an imaging biomarker. We investigated whether IFSHs were tied to Alzheimer’s disease (AD) pathology and cognitive performance. We used data from 361 participants along the AD continuum, who were enrolled in the multicentre DELCODE study. The IFSHs were rated visually based on FLAIR magnetic resonance imaging. We performed ordinal regression to examine the relationship between the IFSHs and cerebrospinal fluid-derived amyloid positivity and tau positivity (Aβ42/40 ratio ≤ 0.08; pTau181 ≥ 73.65 pg/mL) and linear regression to examine the relationship between cognitive performance (i.e., Mini-Mental State Examination and global cognitive and domain-specific performance) and the IFSHs. We controlled the models for age, sex, years of education, and history of hypertension. The IFSH scores were higher in those participants with amyloid positivity (OR: 1.95, 95% CI: 1.05–3.59) but not tau positivity (OR: 1.12, 95% CI: 0.57–2.18). The IFSH scores were higher in older participants (OR: 1.05, 95% CI: 1.00–1.10) and lower in males compared to females (OR: 0.44, 95% CI: 0.26–0.76). We did not find sufficient evidence linking the IFSH scores with cognitive performance after correcting for demographics and AD biomarker positivity. IFSHs may reflect the aberrant accumulation of amyloid β beyond age

Cytokine secretion depends on Galalpha(1,3)Gal expression in a pig-to-human whole blood model

Transplants from alpha1,3-galactosyltransferase (Gal) gene-knockout pigs to nonhuman primates are largely protected from hyperacute but not acute humoral xenograft rejection. The present study investigates the role of Gal in cytokine responses using a novel pig-to-human whole blood in vitro model, developed for species-specific analysis of porcine and human cytokines. Porcine (n = 7) and human (n = 27) cytokines were measured using ELISA or multiplex technology, respectively. Porcine aortic endothelial cells from control (Gal(+/+)) and Gal-deficient (Gal(-/-)) pigs were incubated with human lepirudin anticoagulated whole blood from healthy donors. E-selectin expression was measured by flow cytometry. The C3 inhibitor compstatin and a C5aR antagonist were used to study the role of complement. Cytokine species specificity was documented, enabling detection of 2 of 7 porcine cytokines and 13 of 27 human cytokines in one single sample. Gal(+/+) porcine aortic endothelial cells incubated with human whole blood showed a marked complement C5b-9 dependent up-regulation of E-selectin and secretion of porcine IL-6 and IL-8. In contrast, Gal(-/-) cells responded with E-selectin and cytokine expression which was so weak that the role of complement could not be determined. Human IL-6, IL-8, IFN-gamma, MIP-1alpha, MIP-1beta, eotaxin, and RANTES were detected in the Gal(+/+) system, but virtually no responses were seen in the Gal(-/-) system (p = 0.03). The increase in human cytokine release was largely complement dependent and, in contrast to the porcine response, mediated through C5a. Species-specific analysis of cytokine release revealed a marked, complement-dependent response when Gal(+/+) pig cells were incubated with human whole blood, compared with Gal(-/-) cells which induced virtually no cytokine release

The influence of secondary structure on electron transfer in peptides

A series of synthetic peptides containing 0–5 α-aminoisobutyric acid (Aib) residues and a C-terminal redox-active ferrocene was synthesised and their conformations defined by NMR and circular dichroism. Each peptide was separately attached to an electrode for subsequent electrochemical analysis in order to investigate the effect of peptide chain length (distance dependence) and secondary structure on the mechanism of intramolecular electron transfer. While the shorter peptides (0–2 residues) do not adopt a well defined secondary structure, the longer peptides (3–5 residues) adopt a helical conformation, with associated intramolecular hydrogen bonding. The electrochemical results on these peptides clearly revealed a transition in the mechanism of intramolecular electron transfer on transitioning from the ill-defined shorter peptides to the longer helical peptides. The helical structures undergo electron transfer via a hopping mechanism, while the shorter ill-defined structures proceeded via an electron superexchange mechanism. Computational studies on two β-peptides PCB-(β3Val-β3Ala-β3Leu)n–NHC(CH3)2OOtBu (n = 1 and 2; PCB = p-cyanobenzamide) were consistent with these observations, where the n = 2 peptide adopts a helical conformation and the n = 1 peptide an ill-defined structure. These combined studies suggest that the mechanism of electron transfer is defined by the extent of secondary structure, rather than merely chain length as is commonly accepted. Jingxian Yu, John R. Horsley, and Andrew D. Abel

Organocatalytic Asymmetric Annulation of 1,3-Bis(alkoxycarbonyl)buta-1,3-dienes and Aldehydes

Asymmetric organocatalytic annulation of E/Z isomeric mixtures of bis(alkyl carboxylate)buta-1,3-dienes and aldehydes has been realized via enamine catalysis. In the presence of R,R-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether, excellent stereo- and enantioselectivities were achieved for a broad spectrum of substrates