Author Archive

The first direct metalation of indazoles

Paul Knochel from the Ludwig Maximilians University in Munich has developed a method to directly metalate and then functionalise N-protected indazoles.

Indazole heterocycles are important molecules in medicinal chemistry and methods to functionalise them are widely sought after. Direct metalation of indazoles at their 3 position is often problematic as this can quite easily lead to ring opening and formation of an aminonitrile product. Knochel overcame this problem by using a zinc reagent to form a bis-indazoylzinc compound.

The bis-indazoylzinc compound reacts with a wide range of electrophiles and can also undergo arylation in a Negishi cross-coupling reaction.  In general, such reactions are not possible using normal metalation reagents. Future work will concentrate on the synthesis of biologically active molecules using this methodology.

If you want to find out more then download the ChemComm article, free for a limited period.

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Meet our author… Matthew Gibson

Matthew Gibson is a chemist working at the University of Warwick, UK. His research interests focus on the design of macromolecular structures which can interface with biological systems, and consequently all the work in his group is cross-disciplinary. Matthew took time out from his work to talk to ChemComm…  
 
What initially inspired you to become a scientist?
I was always interested in the natural world, but really only became interested in chemistry during my A-levels. I had two very enthusiastic chemistry teachers who strongly encouraged me. We were able to undertake an extended lab project, and I found myself enjoying the challenge. At university I found myself drawn to the creativity of synthesis and how creative solutions can be used to gain fundamental understanding and innovative solutions.   

What was your motivation behind the work described in your ChemComm article?
In my group, we are very interested in interfacing materials with biological systems. A key challenge is making these materials ‘smarter’, so that they have triggerable/programmable activity, but also to introduce degradability. A major hurdle to this is that the synthetic methodologies to obtain degradable materials are not tolerant to introducing functional groups e.g. biological ligands. Conversely, controlled radical polymerisations are tolerant of most functional groups, but these polymers are inherently non-degradable. To overcome these limitations we developed a methodology to introduce bioreducible (-S-S-) linkages into polymers derived from controlled radical polymerisation. We demonstrated that these polymers have interesting thermoresponsive behaviour, which can be ‘switched off’ by degradation.

Why did you choose ChemComm to publish your work?
I felt that both the synthetic methodology and also the applications of the materials we describe in the article would be of interest to readers with both chemistry and bioscience backgrounds. Considering the broad readership of ChemComm and the rapid publication times, it was really the best place to disseminate this work.

Where do you see your research heading next?
We are now extending the technology from our recent ChemComm paper to develop increasingly complex materials which have triggerable interactions with cell membranes. We are broadening the scope of the monomers used and also undertaking biological studies.

What do enjoy doing in your spare time?
Since I lived in Switzerland for 3 years, skiing and alpine hiking are always top of my list! Otherwise, reading a good book or heading to the movies.

If you could not be a scientist, but could be anything else, what would you be?
It would be something outdoor such as a national park warden, or alternatively running a pub/brewery – in an ideal world, I’d combine the two.

Matthew has recently published two communications in ChemComm touching on the degradable thermoresponsive polymers described here and another on gold and micelle-based polymer nanoparticles.

Degradable thermoresponsive polymers which display redox-responsive LCST Behaviour
Daniel J. Phillips and Matthew I. Gibson
Chem. Commun., 2012, 48, 1054-1056

The critical importance of size on thermoresponsive nanoparticle transition temperatures: gold and micelle-based polymer nanoparticles
Nga Sze Ieong, Konstantinos Brebis, Laura E. Daniel, Rachel K. O’Reilly and Matthew I. Gibson
Chem. Commun., 2011, 47, 11627-11629

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Extension of Hirsch’s rule opens the door on spherical aromaticity

Miquel Solà and Jordi Poater working University of Girona in Spain have put forward an extension of Hirsch’s rule to open-shell spherical species. 

The famous Hückel rule allows one to estimate whether or not a planar ring molecule would have aromatic properties. When the molecule has 4N + 2 π-electrons then it follows Hückel’s rule. In 2000 Andreas Hirsch found a rule to predict the aromaticity of fullerenes, known as the 2(N +1)2 rule and now Solà has extended this rule to spherical systems with an open-shell.

They found that spherical compounds with a half filled last energy level, e.g. those with 2N2 + 2N + 1 electrons, are aromatic. This was backed up with computational evidence and showed that for example C6019+ and C601- both have strong aromatic character.

Solà speculates that this finding could be an important tool for those working in the in stable high spin molecules such as molecular magnets. 

Interested in finding out more? Then download the full ChemComm article for free today.

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Yeast cell wall particles for multi-modal imaging

Scientists based in Italy and Portugal have developed a new carrier system for Magnetic Resonance Imaging (MRI) based on yeast cell wall particles (YCWPs).

YCWPs are well tolerated in vivo because they have a cell wall based on a glucan polymer. However, previous attempts at using it as a carrier of hydrophilic and amphiphilic chemicals have failed due to the porous and hydrophilic nature of the membrane.

In this work the team, led by Enzo Terreno at the University of Turin, realised that they could use the YCWPs as microreactors. Once loaded with an imaging agent the particles were exposed to a sudden change in solvent polarity therefore forming a micro-emulsion inside the particles. Importantly this traps the imaging agent in the particle core.

When loaded with gadolinium, the particles were found to have an increased paramagnetic density and also enhanced relaxivity per paramagnetic centre. In all, this should lead to better contrast when used for imaging. In the future Terreno envisages potential applications in cell tracking experiments and particularly for cells found in the immune system.

Want to find out more? Then download the full ChemComm article for free today.

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Meet our author… Weiping Wang

Weiping Wang is now a Ph.D. student under the supervision of Professor Ying Chau at the Hong Kong University of Science and Technology. He has just passed his Ph.D. thesis defense and has been accepted into a postdoctoral position in Boston area. Weiping took some time out from his work to talk to ChemComm

Chau and Wang’s recent ChemComm article, Efficient and facile formation of two-component nanoparticles via aromatic moiety directed self-assembly,  presents a self assembling system based around Fmoc groups for the construction of nanoparticles.

What initially inspired you to become a scientist?

I grew up in a family of teachers and was influenced by my parents. I became interested in the natural sciences from a very young age. I spent my childhood making simple circuits, performing oil combustion, observing ant behavior. Becoming a scientist was a very natural path for me. After I started my Ph.D. my desire to become a scientist was consolidated. For me, scientific research is the best career in the world. You can accelerate societal development and bring benefits to the human race by investigating topics that interest you.

What was your motivation behind the research described in your ChemComm communication?

Aromatic groups conjugated with small molecules can engage in specific interactions to facilitate self-assembly. However, most synthetic small aromatic molecules self-assemble into nanofibrous structures, which are not suitable as drug delivery carriers. Inspired from the natural protein clathrin, we envisioned that a simple trigonal core molecule conjugated with three aromatic groups may achieve a rapid and efficient assembly into nanoparticles. Moreover, as drug delivery carriers, nanoparticles need to be well-dispersed at physiological conditions. This further motivated us to design this two-component self-assembling system employing aromatic interactions.

Where do you see your research heading next?

The two-step aromatic-directed self-assembling process allows us to introduce biofunctional peptides on the surface of nanoparticles. We have successfully prepared two-component nanoparticles functionalized by Fmoc-modified targeting peptides. The nanoparticles have shown attractive physicochemical and biofunctional properties for drug delivery application. Now the nanoparticles are being evaluated for encapsulating poorly soluble anticancer drugs and in vitro cytotoxicity. The idea of the self-assembling system may also inspire the construction of functional nanomaterials using other aromatic moieties. Other aromatic groups or even aromatic drug molecules may be formulated into a promising drug delivery system using a similar approach.

What advice would you have for young scientists considering a career in science research?

Passion is the most important factor to consider.

What do enjoy doing in your spare time?

Travelling, hiking, swimming and photography

If you could not be a scientist, but could be anything else, what would you be?

I think I would be an entrepreneur and start up a company with friends. I would like to know whether I can run a company well.

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Meet our author… Daniela Iacopino

Daniela Iacopino, a chemist working on organic nanostructures at the Tyndall National Institute, in the Republic of Ireland, takes some time away from her research to speak with us… 

Iacopino’s recent communication in ChemComm reports an advance in the field of photoswitchable nanomaterials and in particular polymer nanotubes: Reversible modulation of photoluminescence from conjugated polymer nanotubes by incorporation of photochromic spirooxazine molecules.

 

What initially inspired you to become a scientist?

I was inspired by my chemistry teacher in school.

What was your motivation behind the research described in your ChemComm communication?

When we started working on the photoswitiching paper we had been working on polymer nanostructures for a while, exploring their photophysical characteristics. We were then interested in observing different functionalities and also studying possible energy transfer processes in novel doped systems.

Where do you see your research heading next?

At the moment we are investigating the manipulation and functionalisation of metal nanorods. We are also working on dark field spectroscopy of single metal nanostructures for sensing applications.

What advice do you have for young scientists considering a career in science research?

Be curious and be patient, I haven’t always been patient but I have always been curious.

What do enjoy doing in your spare time?

I read, run, swim and practise yoga.

If you could not be a scientist, but could be anything else, what would you be?

I’d seriously consider becoming a midwife.

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A step forward for photodynamic therapy

Scientists in the US have developed a new photodynamic therapeutic reagent that works in the absence of oxygen.

Photodynamic therapy (PDT) is an emerging treatment used to eradicate premalignant and early-stage cancer, and also reduces tumour size in end-stage cancers. PDT works by exposing the tissue sample to a light source, which excites the PDT reagent causing singlet oxygen to form due to a reaction with the more common triplet oxygen. The resulting singlet oxygen then invokes cell death in tumour cells. 

The PDT reagent has been designed by Karen Brewer and co-workers from Virginia Tech, where they have shown its capabilities for binding and photocleaving DNA under red light irradiation. The anti-cancer complex [(bpy)2Os(dpp)RhCl)2(phen)]3+ has two metal centres; the osmium portion is capable of photocleaving DNA by singlet oxygen generation and the rhodium part is capable of binding to the DNA in the first place.

Crucially, this is the first complex that works in the absence of oxygen. Tumour cells are often oxygen-depleted environments and therefore a treatment that functions in the absence of oxygen is an important step forward. Future investigations will centre on the bioreactivity of this and other related complexes.

Interested in finding out more? Then download the ChemComm article, which will be free to access until 25th July 2011.

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The first hydroamination reaction with a zincocene complex

Peter Roesky, Siegfried Blechert and co-workers at the Karlsruhe Institute of Technology and the Berlin University of Technology have reported the first use of a dizinc complex as the catalyst in a hydroamination reaction.

Hydroamination is the addition of an N–H bond of an amine to an unsaturated C–C bond to give a molecule that contains nitrogen in one step. This is particularly important because many current amine syntheses are multi-step processes. Zinc complexes are advantageous for hydroamination as they are relatively cheap, air and moisture stable and tolerant to a wide variety of functional groups.

With this in mind Roesky and Blechert decided to test the zincocene complex, Zn25-C5Me5)2, for its hydroamination activity. This complex was discovered in 2004 but it is the first time that it has been used as a catalyst. The team found that the catalyst worked well with good yields and conversions and that it tolerates many functional groups.

Want to find out more? Then download the ChemComm article for free today and leave a comment below.

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New template has potential for bone tissue engineering

British scientists at working at Imperial College, London have synthesised a macroporous hydroxyapatite bioceramic with potential uses in bone regeneration.

Porous hydroxyapatite (HA) bioceramics are widely studied for their potential use in bone regeneration. These materials are biocompatible and have a structure that contains many connected pores. This allows fluid to flow through the material and provides nucleation points for bone growth. The best results are obtained when the the pores are smaller than 1 μm and therefore synthetic methods that give good control over the pore size and material structure are highly desirable.

Prof. Molly Stevens and her team have now demonstrated a way of making an HA bioceramic with a 3D ordered (DOM) macroporous structure. They used an ordered macroporous carbon template (OMC)  in combination with a sol-gel method to form the desired bioceramic. They found that the DOM HA, when compared with HA material made without the OMC template, allowed the nucleation of calcium phosphate on the surface of the pores, thus demonstrating that the template method used affects the crystallisation of material.

hydroxyapatite bioceramics

The team hopes that these materials will find applications not only in the generation of bone but also in the generation of other materials. Want to find out more? Then download the ChemComm article for free today and leave a comment below to let us know what you think.

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New acetylene polymerisation catalyst is best yet

A team of chemists working in the UK and Australia have developed a new, highly active catalyst for acetylene polymerisation.

Polyacetylene is an important material as it has a degree of conjugation that leads to good conductive properties. It has found uses in areas such as synthetic metals and plastic electronics. New routes to make this polymer are constantly sought and, to date, the majority of catalysts for this task have low activities.

This problem has now been solved by two teams at the University of Tasmania and Imperial College London led by David McGuinness and George Britovsek, respectively. They took a bis(imino)pyridine iron catalyst, normally used for ethylene polymerisation, along with methylaluminoxane and successfully produced polyacetylene.

Graphical abstract: High activity acetylene polymerisation with a bis(imino)pyridine iron(ii) catalyst

An activity of 62 500 h-1 (turn over frequency; TOF) was obtained, which compares excellently with the 100  h-1 TOF obtained when using a standard existing acetylene polymerisation catalyst under the same conditions. This represents the most active acetylene polymerisation reported to date. Curently, the team are studying the effects of ligand modification and chain transfer reagents on the reaction.

Want to find out more? Then download  the full ChemComm article for free today.

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