Chemical Science Blog

The self-assembled multivalent complexes (blue) can induce blood clotting by binding to heparin (green)

Recovering from operations could become easier thanks to a self-assembling multivalent heparin binding agent being developed by scientists in the UK, Italy and Spain. 

During some surgical procedures, heparin is given to patients to prevent blood clots from forming by thinning their blood. Protamine is then given following surgery to inactivate heparin and allow healing to begin. However, this drug can have dangerous side-effects, so is often only used in small doses but this can lead to bleeding and further surgery being required. Spending time at the hospital after his husband’s lung transplant gave David Smith at the University of York personal insight into the problems of using protamine and inspired him and his team to devise an alternative. 

The Self-Assembled Multivalent complexes they have created, called SAMul in honour of Smith’s husband, Sam, are made up of molecules containing an ionic heparin binding part and a hydrophobic part. In biological media, the hydrophobic section induces the individual molecules to aggregate into micelles, with multiple heparin binding sites exposed on the micelle surface. This multivalency increases the micelles’ ability to bind heparin. Incorporating an ester linker into the molecules mean they will slowly degrade via hydrolysis if an excess is used, minimising any side effects. 

Read the full article in Chemistry World» 

Read the original journal article in Chemical Science – it’s free to download until 26th March:
Nanoscale self-assembled multivalent (SAMul) heparin binders in highly competitive, biologically relevant, aqueous media
Stephen M. Bromfield, Paola Posocco, Ching W. Chan, Marcelo Calderon, Scott E. Guimond, Jeremy E. Turnbull, Sabrina Pricl and David K. Smith  
Chem. Sci., 2014, Advance Article, DOI: 10.1039/C4SC00298A, Edge Article

An international team of scientists have made a material capable of both piezoelectric and ferromagnetic behaviour. The discovery opens up the possibility of a new class of polarisable and magnetic compounds, and could lead to better devices for storing electronic information.

New data storage techniques are in demand to meet the ever-increasing use of digital information. Present methods rely on the writing and reading of computer bits by electricity, and require a high electrical current. This generates heat so the amount of data that can be stored on a drive is limited by how efficiently the device can be cooled.

The alternating layers of YFeO3 and LaFeO3 give the structure its unusual polarisation properties

One possible solution is to read the bits electronically but write them magnetically, thereby removing the need for high electrical currents and cooling mechanisms. This method requires a material in which the electrical polarisation can be controlled by changing the magnetic field, but so far no such materials have been discovered.

A crucial first step is to find materials that can display both electrical polarisation and magnetisation at the same time, known as multiferroic materials. Multiferroic materials are challenging to make as there is often competition between their electronic structure requirements, which give rise to each property, and they also have strict symmetry conditions for the overall crystal structure of the material, which must be fulfilled.

Electrical polarisation is impossible in materials with a centre of inversion, so breaking the inversion symmetry of the material is crucial for electrical polarisation to occur. As this is a very common property of many materials’ crystal structures, this limits the number of potential compounds capable of showing multiferroic behaviour, and remains a barrier to the possibility of magnetic data writing.

However, the new approach described by Matthew Rosseinsky, from the University of Liverpool in the UK, and colleagues, side-steps this problem by showing how two centrosymmetric perovskite materials can be combined in such a way as to break the inversion symmetry of the whole material. Depositing alternating layers of yttrium iron oxide (YFeO₃) and lanthanum iron oxide (LaFeO₃) using a laser produces a larger heterostructure in which the alternating layers of Y³⁺ and La³⁺ cations combine with the tilting of the FeO₆ octahedra to remove the centre of inversion symmetry.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science – it’s free to download until 25th March:
Engineered spatial inversion symmetry breaking in an oxide heterostructure built from isosymmetric room-temperature magnetically ordered components
J. Alaria, P. Borisov, M. S. Dyer, T. D. Manning, S. Lepadatu, M. G. Cain, E. D. Mishina, N. E. Sherstyuk, N. A. Ilyin, J. Hadermann, D. Lederman, J. B. Claridge and M. J. Rosseinsky  
Chem. Sci., 2014, Advance Article, DOI: 10.1039/C3SC53248H, Edge Article

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

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