Chemical Science Blog

The vaccine ingredients self-assemble into a liposome

A Streptococcus pneumonia vaccine with fewer sugar units and no antigenic protein is not only easier to produce but could also induce a superior immune response to the vaccine currently in clinical use.

Cells are sugar coated; bacteria, parasite and tumour cells often have different carbohydrates to host cells on their surface. Since the immune system recognises these, vaccines can be made of carbohydrates. However, to gain long-term immunity, a protein that provokes an immune response by activating T cells is usually included too. The protein is covalently attached to the carbohydrate, but synthesis of such vaccines can be tricky.

Shenglou Deng, of Brigham Young University in Utah, US, and co-workers, made two main changes with their new vaccine: instead of using the whole sugar on the pathogen’s coat they took a small section of it – an oligosaccharide – and instead of joining this to a protein, they combined it with a lipid that targets only one type of T cell – natural killer T (NKT) cells. Two long chain lipids, to give the vaccine structure, were also added to the vaccine’s ingredients.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science – it’s free to access until 19th March:
A peptide-free, liposome-based oligosaccharide vaccine, adjuvanted with a natural killer T cell antigen, generates robust antibody responses in vivo
S. Deng, L. Bai, R. Reboulet, R. Matthew, D. A. Engler, L. Teyton, A. Bendelac and P. B. Savage  
Chem. Sci., 2014, Advance Article, DOI: 10.1039/C3SC53471E

Immune-labelling combined with imaging MS has provided the first direct evidence of an iron–dopamine interaction in Parkinson's © Shutterstock

Neuron death is an obvious aspect of neurodegenerative disease but a complex puzzle of biological pathways and interactions needs to be teased apart to understand the underlying mechanisms.

Philip Doble, of the University of Technology in Sydney, Australia, and colleagues have unveiled an immune-labelling and imaging mass spectrometry technique to demonstrate the interaction of iron and dopamine in the brain of a Parkinson’s disease (PD) mouse model. They hope their findings may bring researchers closer to understanding and treating this debilitating condition.

PD is caused by the degeneration of dopaminergic neurons in the substantia nigra (SN) region of the brain, causing loss of function, in particular that linked with movement. Iron is known to be present in higher concentrations in the brains of PD patients. ‘We don’t know for certain if this is a cause or consequence of the disease,’ explains Doble, ‘but increasing evidence is pointing to iron playing a major role in the death of dopamine-producing neurons of the SN.’ The interaction of iron and dopamine has been proposed as a neurotoxic mechanism through a redox-couple, which produces free radicals; however, this interaction has proved difficult to study in situ.

By targeting tyrosine hydroxylase (TH), an enzyme involved in dopamine biosynthesis, using a metal-linked immunohistochemical approach, the team successfully quantified the co-localisation of TH and iron in the brain through simultaneous imaging of the two species in a PD model, providing the first direct evidence of this relationship.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science:
An iron-dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta
Dominic J. Hare, Peng Lei, Scott Ayton, Blaine R Roberts, Rudolf Grimm, Jessica L. George, David Bishop, Alison Beavis, Sarah J. Donovan, Gawain McColl, Irene Volitakis, Colin L. Masters, Paul A. Adlard, Robert A Cherny, Ashley Ian Bush, David I Finkelstein and Philip Doble  
Chem. Sci., 2014, Accepted Manuscript, DOI: 10.1039/C3SC53461H, Edge Article

The first fluorescent sensor for radioactive pertechnetate anions has been developed by researchers in Italy and Switzerland.

Technetium-99 (99Tc) is a radioactive product of nuclear fission, whose presence in nuclear waste is a significant concern due to its long half-life. It is mainly handled on an industrial scale as the pertechnetate anion (99TcO4-). If released accidentally, environmental contamination with 99TcO4- can last thousands of years and poses a serious hazard. Valeria Amendola and co-workers at the University of Pavia and the University of Zurich have designed the first supramolecular host molecule that can fluorescently sense the presence of 99TcO4-.

The fluorescence of the receptor is quenched by adding pertechnetate anions

The fluorescence of the receptor is quenched by adding pertechnetate anions

Using a fluorescent probe to sense 99TcO4- could have significant advantages over current radiometric methods using b-counting by liquid scintillation (LSC), explains Amendola. ‘Direct determination of 99Tc by LSC is hard to achieve because of the presence of complex matrices, and sometimes insufficient sensitivity. The high sensitivity of optical chemosensors would allow the detection of low levels of the target anion in contaminated water samples, without special instrumentation.’

Encapsulating 99TcO4- using non-covalent interactions is more challenging than encapsulating…

Read the full article in Chemistry World»

Read the original journal article in Chemical Science:
Fluorescent sensing of 99Tc pertechnetate in water
Valeria Amendola, Greta Bergamaschi, Massimo Boiocchi, Roger Alberto and Henrik Braband  
Chem. Sci., 2014, Accepted Manuscript, DOI: 10.1039/C3SC53504E, Edge Article

Synthesising cyclic carbonates could become easier and more efficient thanks to a sequential flow system developed by scientists in the US.

Cyclic carbonates are used as fuel additives and in lithium-ion batteries, and are key intermediates for pharmaceuticals. However, many current synthesis methods require expensive starting reagents and result in unwanted side products.

The method developed by Tim Jamison, of Massachusetts Institute of Technology in Boston, and coworkers, avoids many of these problems by starting from easily obtainable alkenes, rather than the corresponding epoxides, and the cheap and readily available carbon dioxide. The starting alkene is treated with water and N-bromosuccinimide (NBS), a source of bromide ions, which converts the alkene to a bromohydrin. 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), a base, is then added, followed by CO₂, leading to the formation of the cyclic carbonate.

Introducing reagents at specific stages prevents them from interacting with each other or with reaction intermediates

Read the full article in Chemistry World»

Read the original journal article in Chemical Science:
Mechanism-guided design of flow systems for multicomponent reactions: conversion of CO2 and olefins to cyclic carbonates
Jie Wu, Jennifer A. Kozak, Fritz Simeon, T. Alan Hatton and Timothy F. Jamison  
Chem. Sci., 2014, Advance Article, DOI: 10.1039/C3SC53422G, Edge Article

The movement of molecules in and out of cells is fundamental to the chemistry of life. The process is facilitated by other molecules, specifically designed (or perhaps evolved!) to assist in transportation across the cell wall. It is a complicated process and remains poorly understood yet it is known that disruption of the process is linked to many debilitating diseases, such as cystic fibrosis. As a result, there is significant interest in increasing our understanding of the chemistry involved. Only by doing this will it be possible to create treatments which could, for example, use synthetic carriers to improve transportation in cases where it is restricted.

(a) Varying the position of the anion-binding group (b) Transport activities in synthetic vesicles are measured via the quenching of lucigenin fluorescence by incoming chloride.

Insight into transport of anions across cell membranes is reported in back-to-back Edge Articles in Chemical Science by Philip Gale and his network of collaborators at the University of Southampton, the University of Sydney, the University of Ljubljana and the NMR centre at the National Institute of Chemistry in Slovenia, and the University of Bristol.  In the first paper, Gale’s group and the team of Anthony Davis at Bristol address a new principle, which they refer to as ‘lipophilic balance’.  Anion carriers must have an affinity for the ions they need to transport but, as they discover, the location of that anion receptor within the molecule is also critical.  A central or balanced location with the transport carrier results in a much faster transportation of the anion.

In the second paper, Gale and co-workers team up with Katrina Jolliffe (Sydney), Janez Plavec (Slovenia), and their respective groups to examine transport of a poorly studied anion – sulphate. To do this, they explain how they developed a new method based upon sulphur NMR spectroscopy. This has allowed them to monitor sulphate transportation through differences they observe, both inside and outside of the vesicle. Furthermore, they establish that the movement is assisted by small cyclic molecules that are able to wrap around the sulphate.

The work is also reported through an exciting new website called Kudos – a prototype site which works with selected authors to test the effect on download and social media activity of collating and creating multimedia and additional metadata around articles.  The pilot project, supported by the Royal Society of Chemistry and other publishers, is designed to help scientists enhance the impact of their published work, increasing visibility and discoverability. This is achieved by providing a framework to include supplementary information which is often not possible to include in a journal submission, such as a discussion of the work in lay terms, the wider impact of the work and supplementary information such as videos. The greater accessibility of the work therefore allows the researchers to engage a wider audience and maximise their impact.

Access these two Chemical Science Edge Articles on Kudos today – FREE to read!

Lipophilic balance – a new design principle for transmembrane anion carriers
Hennie Valkenier, Cally J. E. Haynes, Julie Herniman, Philip A. Gale and Anthony P. Davis
Chem. Sci., 2014, Advance Article
DOI: 10.1039/C3SC52962B

Synthetic transporters for sulfate: a new method for the direct detection of lipid bilayer sulfate transport
Nathalie Busschaert, Louise E. Karagiannidis, Marco Wenzel, Cally J. E. Haynes, Neil J. Wells, Philip G. Young, Damjan Makuc, Janez Plavec, Katrina A. Jolliffe and  Philip A. Gale
Chem. Sci., 2014, Advance Article
DOI: 10.1039/C3SC52006D

Ruaraidh McIntosh is a guest web-writer for Chemical Science.  His research interests include supramolecular chemistry and catalysis.  When not working as a Research Fellow at Heriot-Watt University, Ruaraidh can usually be found in the kitchen where he has found a secondary application for his redoubtable skills in burning and profanity.

Researchers in the UK have developed a new method that uses surface enhanced Raman scattering (SERS) to quickly identify which meningitis causing bacteria is responsible for an infection.

Neisseria meningitidis is one of three pathogens that the technique can detect © Shutterstock

Onset of meningitis is often rapid and severe, particularly when a bacterial infection is the cause. Several types of bacteria cause meningitis and each is sensitive to different antibiotics.

The faster the type of bacteria can be identified by DNA analysis, the faster patients can receive the most effective antibiotic for their condition. This also reduces the need for broadband antibiotics, overuse of which is increasing bacterial resistance.

Karen Faulds’ group at the University of Strathclyde, Glasgow, used SERS, a spectroscopic imaging technique, to identify which of Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidisis were present in a single sample, with a view to analysing cerebral spinal fluid from patients suspected to have meningitis. A series of DNA probes containing dyes detectable by SERS make it possible to single out the different pathogens.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science:
Simultaneous detection and quantification of three bacterial meningitis pathogens by SERS
Kirsten Gracie, Elon Correa, Samuel Mabbott, Jennifer A. Dougan, Duncan Graham, Royston Goodacre and Karen Faulds  
Chem. Sci., 2014, Advance Article, DOI: 10.1039/C3SC52875H, Edge Article

© Shutterstock

German scientists searching for a sustainable source of medically important polyunsaturated fatty acids (PUFAs) have shown they can be manufactured by soil-dwelling bacteria.

Research is ongoing to pinpoint who would benefit most from taking a fish oil supplement but there’s no denying that PUFAs – the good fats in fish and fish oil – have clear health benefits. However, overfishing, climate change and ocean acidification have left global fish populations, and supplies of high quality fish oil, in decline.

Rolf Müller and colleagues at Saarland University have identified that certain species of myxobacteria, also known as slime bacteria after the slime they produce to aid their movement, have the genes to synthesise certain omega-3 long-chain PUFAs de novo by employing enzymes known as PUFA synthases.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science:
Polyunsaturated fatty acid biosynthesis in myxobacteria: Different PUFA synthases and their product diversity
Katja Gemperlein, Shwan Rachid, Ronald O. Garcia, Silke C. Wenzel and Rolf Mueller  
Chem. Sci., 2013, Accepted Manuscript, DOI: 10.1039/C3SC53163E, Edge Article

Everyone knows that like charges repel one another. But unusual coordination compounds bearing cationic ligands bound to cationic metals have been prepared by scientists in Israel, opening up fresh opportunities for organic transformations.

Gandelman's team have successfully made rhodium (pictured) and platinum forms of the unusual complexes

When two positively charged chemical species are brought together they experience counteracting forces. One is Coulombic repulsion, and the other is attraction due to the bonding interactions between the nuclei of one cation and the electrons of the other. Thermodynamically unstable bonds ensue from the interplay of these opposing interactions.

Rather than being thermodynamically stable, the transition metal complexes made by Mark Gandelman from the Israel Institute of Technology in Haifa and colleagues manage to be kinetically stable. Pincer-type ligands with nitrenium moieties at their centre, that are essentially the nitrogen analogues of N-heterocyclic carbenes, are central to the complexes’ creation. Computational investigations reveal that the coordination geometry of the pincer ligand provides the kinetic barrier to dissociation of the nitrogen–metal bond; the two phosphine arms aid coordination by bringing the metal within close proximity of the central nitrogen.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science:
Cation-Cation Bonding in Nitrenium Metal Complexes
Mark Gandelman, Yuri Tulchinsky, Prasenjit Saha, Sebastian Kozuch, Mark M Botoshansky and Linda Shimon  
Chem. Sci., 2013, Accepted Manuscript, DOI: 10.1039/C3SC53083C, Edge Article