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Early Alzheimer’s diagnosis compound

20 Dec 2012

Alzheimer’s disease is the most common form of dementia and, as there is no cure, early diagnosis is crucial for treatment to be effective. To this end, UK and US scientists have developed a labelled tracer compound that binds to plaques closely associated with Alzheimer’s disease (AD) so that the plaques can be picked up by a medical imaging technique.

The tracer compound is a [¹⁸F]-labelled barbiturate and is used with the imaging technique positron emission tomography (PET). Although other radiolabelled compounds have been used as PET tracers, using [¹⁸F]-labelled barbiturates for molecular imaging in AD has distinct advantages, such as good blood-brain barrier crossing ability, metabolic stability and easy accessibility.

Tree that looks like a face with some leaves blowing away to represent memory loss in Alzheimer's disease As Alzheimer’s disease advances, symptoms can include confusion, irritability and aggression, and long-term memory loss © Shutterstock

Matteo Zanda at the University of Aberdeen and colleagues, in conjunction with Pfizer in the US, developed several fluorinated barbiturate analogues. The key to developing an effective molecular imaging radiotracer is the ability to distinguish between a healthy individual and someone suffering from a neurological disease, such as AD, they say. Barbiturates have a strong capacity for forming structures with biopolymers and are effective metal ion chelators. As such, the team thought that they would bind to AD-related plaques, which consist of the biopolymer β-amyloid and metal cations, such as Zn(II) and Cu(II).

See the Chemistry World story in full or read the Chem Comm article:

18 F-barbiturates are PET tracers with diagnostic potential in Alzheimer’s disease
Elisa Calamai , Sergio Dall’Angelo , David Koss , Juozas Domarkas , Timothy J. McCarthy , Marco Mingarelli , Gernot Riedel , Lutz F. Schweiger , Andy Welch , Bettina Platt and Matteo Zanda
Chem. Commun., 2013,49, 792-794
DOI: 10.1039/C2CC38443D

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Nanoconfinement leads to increased catalytic stability

29 Nov 2012

Steam reforming, where hydrogen gas is produced from hydrocarbon fuels such as natural gas, is an important industrial catalytic process. Nickel is the catalyst of choice due to its low cost and high C-C bond rupture activity, and zirconia (ZrO₂) is widely used as the catalytic support due to its thermal and chemical stability, moderate acidity and surface oxygen mobility. The same supported Ni/ZrO₂ catalyst is a promising candidate for ethanol steam reforming (ESR), but its deactivation caused by sintering and coke deposition remains a problem.

Jinlong Gong and researchers from Tianjin University used a surfactant-assisted method to prepare a nanocomposite Ni@ZrO₂ catalyst made up of nickel nanoparticles distributed evenly throughout a similarly sized zirconia matrix. The new catalyst demonstrated higher activity and selectivity for the conversion of ethanol into CO₂ and H₂. Almost complete conversion of ethanol over a 50 hour period was observed, while the activity of the traditional Ni/ZrO₂ catalyst decreased continually after just six hours.

The even distribution of metal nanoparticles throughout the matrix allows the pore structure of the solid to be maintained while increasing the accessibility of the catalytically active nickel. The larger metal-oxide interface promotes the removal of carbon deposits while the “confinement effect” prevents the nickel metal from sintering. As highlighted in a recent C&EN article, these promising catalytic properties suggest that the synthetic methodology may be useful for the design of metal catalysts for other processes, such as dehydrogenation, that encounter similar problems.

Read this HOT Chem Comm article today (free to access until the 27th December):

A Ni@ZrO₂ nanocomposite for ethanol steam reforming: enhanced stability via a strong metal-oxide interaction
Shuirong Li, Chengxi Zhang, Zhiqi Huang, Gaowei Wu and Jinlong Gong
Chem Commun., 2013, Advance Article
DOI: 10.1039/C2CC37109J

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Spinks Symposium 2013: Regenerative Medicine – registration open

28 Nov 2012

28 January 2013

Chemistry Centre, Burlington House, London

The therapeutic promise of regenerative medicine, as a way to restore aging or damaged tissues and organs, is one of the most exciting areas of medicines research. With the proportion of older people increasing, degenerative and chronic diseases are a major challenge. To move forward, the chemical sciences have a vital role to play in understanding

disease mechanisms
signalling of stem cells
cellular differentiation
new methodologies for surface modification

The 2013 Spinks Symposium will explore the critical issues that underpin developments in regenerative medicine and provide a clear understanding of the challenges involved in translating research outputs into application. Particular emphasis will be put on how medicinal chemistry/chemical biology research might provide a springboard to therapeutic development. Researchers from industry, academia and the wider health sciences sectors will join together for this stimulating workshop, including oral presentations discussion groups, flash presentations and a comprehensive poster session.

How can I get involved?

Abstracts for the poster programme are now invited. Take full advantage of this exceptional opportunity to present your work and submit before Friday 21st December.
Registration is also open and if you would like to benefit from the early bird rates be sure to secure your place before Friday 21st December

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Cooperative Effects Enhance Biphasic Catalysis

28 Nov 2012

Commodity chemicals are often produced using catalysts. Despite the many advantages of using catalysts (such as faster conversion, improved selectivity) a major difficulty is separating them from the product at the end of the reaction. Such is the significance of this problem, heterogeneous catalysts are often chosen ahead of their homogeneous brothers because they are simpler to remove at the end of the reaction, despite the homogeneous catalysts generally having better performance.

Figure 1 Crystal packing diagram of a POM-phosphazene aggregate.

An alternative solution to the separation problem is to utilise a biphasic solvent system. Partitioning the catalyst and product into different phases provides inherent separation and removes the need for expensive procedures like distillations. Ivan Kozhevnikov and Alexander Steiner at the University of Liverpool have collaborated to join their respective areas of expertise together and create catalytically active polyoxometalate (POM)-phosphazene aggregates (Figure 1) which can operate in a biphasic environment. Their communication reports rapid oxidation of test substrates by enhancing the transfer of the catalytically active POM across the two phases. Furthermore, the chemistry is “green” as it utilises relatively environmentally benign conditions.

The components of the aggregates are independently soluble in the different phases; therefore defining how this catalyst operates will be paramount to understanding and developing the system further. For example, reporting the performance of the POM or the phosphazene independently in the biphasic system would provide essential support to the claim that these aesthetically pleasing aggregates are responsible for the observed catalytic activity and remove some of the alternative potential sources.

Read the ‘HOT’ Chem Comm article today (Free to access until the 27th of December):

Novel polyoxometalate–phosphazene aggregates and their use as catalysts for biphasic oxidations with hydrogen peroxide

Michael Craven, Rana Yahya, Elena Kozhevnikova, Ramamoorthy Boomishankar, Craig M. Robertson, Alexander Steiner and Ivan Kozhevnikov
Chem. Commun., 2012, 48, Advance Article
DOI: 10.1039/c2cc36793a

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Drug delivery: implications of gold-protein interactions

19 Nov 2012

Researchers in Italy have shown that medicinal gold compounds interact strongly with the proteins of the copper trafficking system, which could have implications for drug delivery.

The copper trafficking system consists of proteins that help the uptake of copper into cells and then promote its transfer and delivery to copper-dependent cellular proteins. One of these ‘chaperones’ is known as Atox-1.

Previous work has shown that platinum-based anticancer drugs strongly interact with copper trafficking system proteins and Messori and co-workers hypothesised that medicinal gold compounds might also do the same, especially in the +1 oxidation state; soft lewis acids, such as gold (I) ions react eagerly with Atox-1.

The interactions of three gold (III) compounds with Atox-1 were analysed through ESI-MS and revealed the formation of metal-protein adducts. The same major adduct was invariantly formed, matching the protein binding of a single gold (I) ion. Formation of this adduct implied that the gold (III) complex had broken down, a loss of ligands and reduction to a gold (I) species. ESI-MS also displayed peaks that corresponded to protein binding with two gold (I) ions. A stability study showed that one of the three gold-protein adducts was stable over 72 hours.

From their findings, the authors conclude that the cytotoxic gold compounds investigated form stable adducts with copper chaperone, Atox-1. These results have implications for medicinal drug design and our little friend, Atox-1 stays in a job.

Read this HOT Chem Comm article today (free to access until the 14th of December 2012):

Medicinal gold compounds form tight adducts with the copper chaperone Atox-1: biological and pharmacological implications
Chiara Gabbiani, Federica Scaletti, Lara Massai, Elena Michelucci, Maria A. Cinellu and Luigi Messori
Chem. Commun., 2012, 48, 11623-11625

Published on behalf of Sarah Brown, Chemical Communications web science writer.

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Metal Free Thiolation Reactions of a Series of Heteroaromatics

12 Nov 2012

Aromatic compounds substituted with a C-S bond are of importance for pharmaceutical and medicinal chemistry, and materials science. A widely employed route to such compounds is a cross coupling reaction, between an aryl halide and a thiol, to yield a thioether. The reaction is usually mediated and catalysed by a metal centre such as palladium, indium or nickel, present as a salt or complex. In this communication, the authors report a high yielding, transition metal free route to aryl thioethers, using just a disulfide and a weak base, in a suitable solvent, under an inert gas.

The authors proved early in their study that a metal salt was not required for reactivity, with better yields being recorded for such reactions, versus a metal salt containing control. A further control reaction was carried out, to disprove the presence or effect of any trace transition metal by using ultrapure caesium carbonate (99.994% purity) and freshly distilled solvent.

The model reaction investigated and optimised was the thiolation of 2-phenyl-1,3,4-oxadiazole with di-p-tolyl disulfide. Reaction conditions which gave the best yields involved the use of 2 equivalents of base and 1,4-dioxane as solvent, under an argon atmosphere, for typically 18-24 h. 5 equivalents of disulfide were found to be the most effective. Using 7 equivalents gave no benefit to the final yield. Coincidently, the excess disulfide proved easily recoverable from the reaction mixture.

Electronic effects proved to be important in the reactivity of the phenyl-oxadiazoles with electron donating groups present on the arene promoting the reaction and electron withdrawing groups having a negative effect. The reaction also shows a good degree of robustness in being effective in thiolating indole and 5-methyl-indole at the 3 positions in excellent yield, as well as other substrates such as caffeine and benzimidazole.

This synthetic methodology represents an important simplification in the preparation of heteroaromatic thioethers, and should prove of interest to synthetic chemists, particularly in the areas of medicinal chemistry, materials science and total synthesis.

Read this HOT Chem Comm article today (free to access until the 7th of December 2012):

Transition metal-free direct C–H bond thiolation of 1,3,4-oxadiazoles and related heteroarenes

Liang-Hua Zou, Jens Reball, Jakob Mottweiler and Carsten Bolm, Chem. Commun., 2012, 48, 11307–11309

Published on behalf of Kevin Murnaghan, Chemical Communications web science writer.

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Origami, without the papercut, visualised

07 Nov 2012

Researchers in China have been able to visualize the intracellular location of DNA origami with a label-free fluorescent probe.

But let’s unfold a few things first and figure out what that means. DNA origami is the folding of a strand of DNA to make arbitrary 2 or 3 dimensional shapes; this serves as a ‘scaffold’ for shorter DNA strands that help hold the structure in its folded shape. These structures may be used for drug delivery, biosensors and more. I once made an origami frog; I wonder if there are any similarities…

Direct visualisation of the distribution and stability of DNA origami in live, cellular systems has not been achieved. Fluorescent labels can be attached to DNA strands but these have their drawbacks, such as weak emission intensity, photobleaching and expensive. Ding and co-workers looked at alternatives to visualize DNA origami in live cells.

The group were inspired by research on a series of carbazole-based cyanine fluorescence probes, which have a weak emission when they are monomolecularly dissolved but switch to a strong luminescent state upon binding to DNA or protein molecules. The significant enhancement is attributed to restricted intramolecular rotational (RIR) motions by anchoring the DNA molecules, which causes the large reduction in the non-radiative decay of fluorescence molecules.

Follow the instructions (a) and you too won’t make DNA-origami visualised in cells (b)

Ding and co-workers then took some tubular DNA origami, the cyanine fluorophore and found that the carbazole-based cyanine molecules could be used as a sensitive optical switch, turned on when DNA origami is detected and turned off when the nanostructure degrades. After incorporating the cyanine probe molecules, the DNA origami-probe complex was administered to live cells. Excitingly, the green-yellow frog… erm, I mean, fluorescence was visible inside the cells treated with the probe. The group went further to try and understand the internalization mechanism of the DNA origami and found the probe localized in lysosomes. Finally, degradation studies showed that most DNA origami were dissociated after 60 hours, also a bit like my origami frog.

Unlike my attempts at origami, Ding and co-workers have demonstrated an exciting step in scaffolded DNA origami and its future applications in nanomedicine.

Read this HOT Chem Comm article today (free to access until the 5th of December 2012):

Visualization of the intracellular location and stability of DNA origami with a label-free fluorescent probe
Xibo Shen, Qiao Jiang, Jinye Wang, Luru Dai, Guozhang Zou, Zhen-Gang Wang, Wei-Qiang Chen, Wei Jiang and Baoquan Ding
Chem. Commun., 2012, 48, 11301-11303

Published on behalf of Sarah Brown, Chemical Communications web science writer.

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Flexible post-synthetic approach to functionalised MOFs

06 Nov 2012

Metal-organic frameworks (MOFs), formed from the assembly of metal ions and organic bridging ligands, often have large pores and high surface areas. Such properties are attractive for various potential applications from gas storage to catalysis. The diverse structures and properties of MOFs can be extended by incorportaing functional groups onto the organic linker after MOF formation through post-synthetic modification.

MIL-101(Cr), a MOF first reported by Ferey et al. in 2005, exhibits mesoporous cages with accessible metal sites as well as high chemical and hydrothermal stability. Amine functionalisation of the framework’s benzene dicarboxylate ligands has been reported for analagous iron and aluminium frameworks, but has so far proven elusive for MIL-101(Cr).

Burrows et al. from the University of Bath have synthesised MIL-101(Cr)-NH₂ using a hydrothermal method, and found that the resultant framework is stable up to 250 °C and, most interestingly, is stable to acids. This unusual stability has allowed them to post-synthetically transform the amine group into an arenediazonium salt which they used in situ to generate a variety of functional groups. MIL-101(Cr)-azo, in particular, showed excellent CO₂ selectivity at low pressure.

This new approach to post-synthetic modification has provided a flexible route to functionalised MIL-101 materials, with further studies concentrating on selected frameworks already underway.

Read this HOT Chem Comm article today (free to access until the 7th of December 2012):

Synthesis and post-synthetic modification of MIL-101(Cr-NH₂) via a tandem diazotisation process

Dongmei Jiang, Luke L. Keenan, Andrew D. Burrows and Karen J. Edler
Chem. Commun., 2012, Advance Article
DOI: 10.1039/c2cc36344e

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The Cram Lehn Pedersen Prize in Supramolecular Chemistry – Nominations Open

26 Oct 2012

2013 ISMSC-8 Crystal City, Virginia 7 July – 11 July, 2013

The International Committee of the International Symposium on Macrocyclic and Supramolecular Chemistry is pleased to invite nominations for the Cram Lehn Pedersen Prize for young supramolecular chemists.

The Cram Lehn Pedersen Prize, named in honour of the winners of the 1987 Nobel Prize in Chemistry, will recognise signicant original and independent work in supramolecular chemistry.

Those who are within 10 years of receiving their PhD on 31st December 2012 are eligible for the 2013 award. The winner will receive a prize of £2000 and free registration for the ISMSC meeting in Crystal City, Virginia. In addition to giving a lecture at ISMSC, a short lecture tour will be organised after the meeting in consultation with the Editor of Chemical Communications, the sponsor of the award.

Nomination Details:

Please send your CV, list of publications (divided into publications from your PhD and post-doc and those form your independent work), and if desired, letter of support, or these materials for someone you wish to nominate to Prof. Roger Harrison (ISMSC Secretary) at rgharris@chem.byu.ed by 31st January 2013.

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Medicinal hope for injectable hydrogels

08 Oct 2012

Injectable hydrogels with dual ionic properties, biodegradability and low cytotoxicity have been developed by South Korean scientists to deliver proteins therapeutically.

Doo Sung Lee and colleagues from Sungkyunkwan University developed an amphoteric copolymer to form dually cationic and anionic hydrogels, in response to pH and temperature changes. The amphoteric nature of the polymer means it should bind to both cationic and anionic biomolecules, and helps sustained co-delivery of them.

The copolymer changing from sol to gel

Read more in Chemistry World or download Lee’s communication in ChemComm.

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