Author Archive

Probing cells’ power generators

UK scientists have developed a probe to monitor bicarbonate concentrations in mitochondria – components in living cells that generate chemical energy. Monitoring bicarbonate levels will improve researchers’ understanding of its role in cellular reaction mechanisms. 

A challenge when designing cellular probes is ensuring that the probe is not only selective for its target but can also be delivered to the site of interest within the cell. A team of scientists led by David Parker at the University of Durham has made a probe that can overcome this challenge. 

Stained HeLa cellsThe luminescent probe features an azaxanthone moiety, which is linked to a europium complex by an amide bond. The azaxanthone allows the probe’s uptake into cells and localisation within the mitochondria, and the europium complex has an affinity for bicarbonate ions. The ability to probe bicarbonate levels ‘can offer an unprecedented insight into signalling mechanisms’, says Parker.

Read the rest of this story in Chemistry World and download Professor Parker’s ChemComm communication, which is free to access for a limited period.

Also of interest:
Definition of the uptake mechanism and sub-cellular localisation profile of emissive lanthanide complexes as cellular optical probes
Elizabeth J. New, Aileen Congreve and David Parker, Chem. Sci., 2010, 1, 111-118

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Across the barrier for tumour imaging

Brain and structure of nanoprobeA probe that can cross the blood-brain barrier to allow high sensitivity brain tumour imaging has been made by Chinese scientists. The probe could be used to pinpoint the location and extent of a tumour before an operation and be used for image-guided tumour removal. 

Establishing the position, extent and structure of brain tumours is crucial for their successful removal. But, current tumour imaging agents used in magnetic resonance imaging are limited by short circulation lifetimes, non-targeted specificity and poor blood-brain barrier permeability. The results of these limitations are that low grade tumours and 20-30 per cent of advanced brain tumours with an intact blood-brain barrier go unnoticed.

Cong Li from Fudan University, Shanghai, and his team made the probe starting with a dendrimer – a branched molecule with a long circulation lifetime – and attached functional groups with different tasks. One such group, a lipoprotein ligand angiopep-2, helps to deliver the probe across the blood-brain barrier and targets the lipoprotein’s receptors, which are present in increased amounts on tumour cells. High-resolution images can be generated thanks to imaging reporters, including fluorescence dyes, attached to the dendrimer. 

Read the rest of this story in Chemistry World and download Li’s ChemComm communication, which is free to access for the rest of the month.

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New sensor for naked-eye fluoride detection

Fluoride, in its organic and inorganic forms, has been increasingly present in the food and beverage chain over the years. It has been added to toothpastes to prevent cavities; different forms of fluoride have been included in pesticides; several categories of food, including cereals, have been fortified with fluoride and even water for public consumption has been artificially fluorinated for decades.

Graphical abstract: A highly selective colorimetric and ratiometric fluorescent chemodosimeter for imaging fluoride ions in living cellsDespite being a useful supplement to support the healthy growth of hair, nails and teeth and the strengthening of bones, an excessive intake of fluorine can lead to adverse effects on development. It can cause mottling of teeth and skeletal fluorosis (causing joint pain and abnormalities in the skeletal structure). Other effects have only been studied in animal models and at concentrations unlikely to be encountered by humans.

Regardless of the debate about its toxicity, it cannot be denied that as such a ubiquitous chemical in the human food chain, the development of simple methodologies and techniques to accurately detect the concentration of this anion in vivo plays an important role in biochemical research.

One of these techniques employs the use of fluorescent indicators that detect the presence of fluoride anions in solution.

Recent research by the Chinese group of Ma, Du and Zhang has been focused on the realisation of a novel “chemodosimeter” for fluoride that responds to the requisites of ease of synthesis, activity in highly aqueous solutions and buffers, cell permeability, quantitative response and high selectivity.

Their sensor, incorporating benzothiazolium hemicyanine as the fluorophore, was tested in fluorine detection in water:ethanol solutions (7:3) containing phosphate buffered saline at a pH of 7.4. In these conditions, the fluorescence of the sensor was not only quantitatively responsive to changes in fluoride concentration, but showed a change in the fluorescence spectrum, with emission at a different wavelength when in presence of the analyte and even noticeable to the naked eye. The versatility and selectivity of the system was also assessed by performing competition experiments in the presence of other anions, such as CO32-, SO42-, NO3, Cl, I and selected aminoacids and proteins like cysteine and human serum albumin, demonstrating a remarkable preferential response for fluoride.

Tests were also performed on living cells in order to determine the cytotoxicity of the chemodosimeter, using HeLa cells as the test substrate, showing low toxicity under the operational conditions.

The selectivity over different anions and analytes of biological relevance, the ability to operate in strongly aqueous solutions, the reliability and quantitative response and the applicability to living cells may make this new chemodosimeter a beneficial tool for biomedical researchers.

To find out more, read the full article:

A highly selective colorimetric and ratiometric fluorescent chemodosimeter for imaging fluoride ions in living cells
Baocun Zhu, Fang Yuan, Rongxia Li, Yamin Li, Qin Wei, Zhenmin Ma, Bin Du and Xiaoling Zhang
Chem. Commun., 2011, DOI: 10.1039/C1CC11308A

Posted on behalf of Dr. Giorgio De Faveri, Web Writer for Catalysis Science & Technology.

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Cram Lehn Pedersen Prize – now open for nominations

 

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Imaging brain tumours

A new probe for imaging brain tumours could offer increased hope for cancer patients, say Chinese chemists.

Den-Angio visualizes an orthotopic U87MG tumor non-invasively in vivo. (A) NIR fluorescence and X-ray/color coded NIR fluorescence images of a mouse head at 2 h PI of Den-Angio. Arrows point to the tumor. (B) T1-weighted MR images of a mouse brain (coronal plane) at 2 h PI of Den-Angio or Gd3+–DTPA with the same gadolinium dose (0.05 mmol kg−1). White arrows point to the tumor and red arrows point to the cerebral ventricle. (C) Histological H&E staining of identical brains in panel B. Scale bar, 2 mm.Cong Li, at Fudan University, Shanghai, and colleagues have made a dendrimer-based nanoprobe called Den-Angio that can cross the blood-brain barrier. It can be used in the magnetic resonance imaging of brain tumours and should make it easier for doctors to distinguish cancerous tissue from healthy cells when cutting out the tumour.

To find out more, read Li’s ChemComm communication.

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Ibuprofen: anticancer drug

Scientists in the UK have moved a step closer to understanding how ibuprofen could help treat cancer. The findings could lead to the drug being used as a preventative treatment for prostate cancer, in the future.

Ibuprofen – a common painkiller – can help reduce the risk of prostate cancer, but the mechanism by which it inhibits tumour cells is still not fully understood. Now, Matthew Lloyd and his team from the University of Bath in the UK, in collaboration with Cancer Research UK, have uncovered a mechanism suggesting that the chiral inversion of ibuprofen inhibits the activity of the protein alpha-methylacyl-CoA racemase (AMACR), levels of which are increased in the presence of prostate, some colon and other cancers.

To find out more, read the full news story in Chemistry World and download Lloyd’s ChemComm communication.

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Macrocycles for in vivo zinc sensing

Graphical abstract: Modular ‘click’ sensors for zinc and their application in vivoZinc anions are ubiquitously present in the body and involved in many metabolic pathways affecting the proper functioning of the immune system, DNA transcription, reproduction, sexual development, brain function, and more roles are uncovered by studies worldwide.

The presence of abnormally high or low level of zinc in specific organs and areas has been linked to several diseases and conditions, including Alzheimer’s disease, stroke and epilepsy. In the light of these considerations, it is not surprising that many efforts have been devoted to in vivo zinc sensing and quantification.

A significant portion of the research to uncover the correlations between the concentration of metal ions, pathologies and development is performed on animal models such as zebrafish (Danio rerio). Due to their fast development, they can be grown outside the mother’s body, and their embryos are transparent, allowing for a clear observation of their organs without the need for dissection.

Watkinson and Goldup, from Queen Mary University of London, recently focused their effort to the development of a fluorescent sensor for zinc to be used in model studies on zebrafish. The sensor is based on macrocyclic nitrogen-containing rings (cyclen or cyclam) equipped with a fluorescent pendant arm, introduced using a widely known and applied “click” cycloaddition. The sensor’s fluorescence is activated upon coordination of the zinc anion in a scorpionate fashion.

The sensors proved reliable and stable in a wide range of pH, ideal for in vivo use, and a remarkable selectivity for zinc over other possible anions. Competition experiments with twelve different anions showed that only in the presence of Fe3+ and Cu2+ in threefold excess (in relation to zinc) the sensor failed to discriminate between the metals.

To test their performance in biological models, zebrafish eggs were grown in solutions of the sensors and the distribution of fluorescence monitored during their growth, proving not toxic to the subjects. The accumulation of fluorescence concentrated in the eye, the gall bladder and the biliary system, all regions not highlighted by previous sensors, suggesting a different mechanism of absorption for these macrocyclic compounds and different cell permeability.

Although those reported are preliminary results, the characteristics of these sensors may make them a viable candidate for future applications in vivo sensing of zinc pools.

Read the article online or access the ESI (free).

Modular ‘click’ sensors for zinc and their application in vivo
Kajally Jobe, Caroline H. Brennan, Majid Motevalli, Stephen M. Goldup and Michael Watkinson
Chem. Commun., 2011, 47, 6036-6038

Posted on behalf of Dr. Giorgio De Faveri, Web Writer for Catalysis Science & Technology 

This communication is part of the ChemComm Supramolecular Chemistry web themed issue. Check out the web theme page to download other contributions from this exciting issue.

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Supramolecular Chemistry—Introducing the latest web themed issue

Graphical abstract: Supramolecular Chemistry—Introducing the latest web themed issueChemComm issue 21 is now online and includes an Editorial from Philip Gale, Jonathan Sessler and Jonathan Steed, guest editors of the recent Supramolecular Chemistry web themed issue.

Featuring over 60 articles (and growing!), the web theme showcases a collection of cutting edge contributions by international leaders in the field of supramolecular chemistry to mark the International Year of Chemistry 2011.

Browse this exciting web theme today to read the latest urgent communications. You can also catch up on a decade’s worth of progress in supramolecular chemistry by reading the issue’s Highlights in Chemistry.

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Call for communications: Artificial Photosynthesis

We are delighted to announce a forthcoming web themed issue:

Artificial Photosynthesis

Guest editor: Andrew Benniston (Newcastle University)

Submission deadline: 15th August 2011 EXTENDED TO 30TH SEPTEMBER!!

We are now welcoming submissions for this web theme, which will be a celebration of current achievements and future perspectives in this exciting field of research. Communications covering all aspects of the following areas are encouraged:

  • new materials and photocatalysts for solar photochemistry
  • hydrogen production and water splitting
  • nitrogen and carbon dioxide functionalisation
  • light harvesting and energy transfer
  • electron transfer (tunnelling vs hopping)
  • coupled proton/electron transfer
  • long-range electron transport
  • multi-electron redox processes
  • bioinspired molecular systems
  • nanostructures for solar energy usage

All manuscripts will undergo strict peer review and should be very important and conceptually significant in accord with the ChemComm mandate.

Publication of the peer-reviewed articles will occur without delay to ensure the timely dissemination of the work. The articles will then be assembled on the ChemComm website as a web-based thematic issue, to permit readers to consult and download individual contributions from the entire series.

Communications for this web theme can be submitted anytime from now until 30th September using our web submission system. Please add the phrase ‘artifical photosynthesis’ in the comments to the editor field.

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New nerve agent sensor to join fight against terror

Graphical abstract: Chemical functionalization of electrodes for detection of gaseous nerve agents with carbon nanotube field-effect transistorsA new sensor for detecting nerve agents has been developed by scientists in France.

Organophosphorus (OP) compounds, such as sarin, are extremely neurotoxic compounds that have been used both in the battlefield and in terrorist attacks, including the Tokyo subway attack in 1995.

Current technologies for detecting OPs are not very practical, say Jean-Pierre Simonato (CEA Grenoble) and colleagues, so they’ve developed a new sensor based on carbon nanotube field-effect transistors.

Find out more in Simonato’s recently published ChemComm communication, free to download until 2nd June.

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