Archive for the ‘Chemistry World articles’ Category

Organic chemistry’s complexity conundrum

Organic synthesis is often heralded as more art than science. An organic chemist’s eye for complexity, breaking down structures into simpler forms, is honed and nurtured over decades. But, is it possible to take this seemingly intangible skill and quantify it, putting a simple number on how complex a chemical structure actually is?

Process chemists Martin Eastgate and Jun Li, at Bristol-Myers Squibb (B-MS) in the US have developed a tool to do just that, generating a unique index they have termed a molecule’s current complexity, which also accounts for changes over time due to the impact of new technologies.


Read the full Chemistry World story»

Read the original Organic & Biomolecular Chemistry article – it’s free to access until 2nd July:
Current complexity: a tool for assessing the complexity of organic molecules

Jun Lia and Martin D. Eastgate
Org. Biomol. Chem., 2015, DOI: 10.1039/C5OB00709G

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Cyanide test for cassava

A new sensing system that changes colour to indicate if a cassava-based foodstuff is safe to eat by checking for hydrogen cyanide has been devised by researchers in Switzerland and Mozambique.

Cassava, an edible root that grows well in poor conditions, is the third largest source of calories for people in the tropics. However, as a self-defence mechanism against attack from pests and predators, cassava releases hydrogen cyanide upon damage to its cells. Sun-drying, fermentation and other traditional processing techniques can successfully eliminate the hydrogen cyanide but it may remain and cause a variety of illnesses, including tropical ataxic neuropathy and epidemic spastic paraparesis, if pre-consumption treatment is substandard…..

Read the full article in Chemistry World»


Read the original journal article in Organic & Biomolecular Chemistry – it’s free to access until 4 December:
Corrin-based chemosensors for the ASSURED detection of endogenous cyanide
Felix Zelder and Lucas Tivana
DOI: 10.1039/C4OB01889C

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How green tea helps lower cholesterol

(–)-epigallocatechin-3-gallate (EGCG) fitting into triangular binding pockets within three different enzymes to inhibit cholesterol biosynthesis

ECG and EGCG (shown) fit into triangular binding pockets within three different enzymes to inhibit cholesterol biosynthesis

Green tea is good for you, but why? Scientists in China are trying to answer one aspect of this huge question by pinpointing which components of green tea help lower cholesterol levels, as well as how they do it.

Green tea has been used in traditional Chinese Medicine for centuries and many studies have demonstrated its numerous health benefits, including its positive action against cardiovascular and neurodegenerative diseases. Polyphenolic compounds constitute most of green tea’s chemical content and have been linked to the disruption of cholesterol biosynthesis in vivo. However, there are so many different compounds in green tea that it has been difficult to work out which ones are active and exactly how these affect biological function.

Jun Xu and colleagues at Sun Yat-Sen University tested the activity of three enzymes that are essential for cholesterol biosynthesis in vitro in the presence of four different polyphenols found in green tea. They found that two polyphenols, (–)-epicatechin-3-gallate (ECG) and (–)-epigallocatechin-3-gallate (EGCG), could inhibit all three enzymes simultaneously, whereas the other two polyphenols had no effect.

Read the full Chemistry World story, including expert comments,

and,

Download the paper for free until 12 June 2014:

Mechanistic studies for tri-targeted inhibition of enzymes involved in cholesterol biosynthesis by green tea polyphenols

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Oliver Kappe: Freedom to explore

Oliver Kappe is professor of chemistry at the University of Graz in Austria. Research in the Kappe group focuses on enabling technologies for synthesis, including microwave and continuous flow methods.

Read some of his recent work in OBC and Green Chemistry:

A three step continuous flow synthesis of the biaryl unit of the HIV protease inhibitor Atazanavir

Design and evaluation of improved magnetic stir bars for single-mode microwave reactors

On the mechanism of the Dakin–West reaction

Nanocatalysis in continuous flow: supported iron oxide nanoparticles for the heterogeneous aerobic oxidation of benzyl alcohol

Direct aerobic oxidation of 2-benzylpyridines in a gas–liquid continuous-flow regime using propylene carbonate as a solvent

Can you tell us what inspired you to become a scientist?

In my case it was pretty straightforward since my father was also a professor of organic chemistry at the University of Graz. It’s a family affair!

What led you towards microwave chemistry in particular?

At a conference in 1998 in Hungary I heard a lecture by Professor Rajender Varma, now at the US EPA, highlighting the benefits of doing organic chemistry under microwave conditions. At that time it was all kitchen microwaves, there was almost nothing else available. That same year we started our collaboration and the following year published our first joint paper together.

I liked it so much that we continued in many different areas. We studied fundamental issues, such as the occurrence of special microwave effects, as well as the application of microwave chemistry in organic synthesis and fields like peptide chemistry, nanomaterials, polymer synthesis. And of course, finally, we looked at how to scale-up microwave chemistry.

Expand to read more of this interview…

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Mutant enzymes help break cocaine habit

An enzyme modified to hydrolyse cocaine 1000 faster than it did before could form the basis of the first medicinal treatment for cocaine addiction. Not only can the enzyme swiftly chop cocaine into inactive metabolites but modification of the enzyme has not affected its selectivity towards other natural substrates.

A treatment for cocaine abuse could be on the horizon © Shutterstock

A treatment for cocaine abuse could be on the horizon © Shutterstock

Cocaine is one the most widely used illegal drugs in the world. Unlike many other commonly abused substances, there are no proven medications available to treat cocaine addition. The health consequences of cocaine abuse are severe and addicts can cause significant societal problems. Finding an addiction treatment is therefore of the utmost importance.

Substrate selectivity of high-activity mutants of human butyrylcholinesterase
Chang-Guo Zhan et al.
Org. Biomol. Chem., 2013, Advance Article
DOI: 10.1039/C3OB41713A

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Hydrogel treatment targets tumours

Hydrogels of cancer drug taxol injected directly into tumours have been shown to be more effective at inhibiting tumour growth than intravenous taxol injections of four times the dosage.

target-injection-bullseye_shutterstock_101348851_300

Taxol is used to treat many forms of cancer, including breast, lung and ovarian cancer. Its administration is typically every three weeks by intravenous injection and it can take several hours to achieve the required dose.

Hydrogels have great potential to reduce the dosing frequency of chemotherapy. They can hold exceptionally high drug loadings that are released in a controlled and sustained manner. However, synthesising such hydrogels is complex, ultimately resulting in low yields.

Zhimou Yang and fellow researchers at Nankai University in China have successfully simplified the synthesis of taxol hydrogels. Their hydrogel contains taxol conjugated to folic acid. The folic acid facilitates tumour targeting as many cancer cells have folic acid receptors so the hydrogels will sustainably release their taxol cargo through ester bond hydrolysis at the site of cancer cells.

Read the full article on Chemistry World.

Disulfide bond reduction-triggered molecular hydrogels of Folic acid-Taxol conjugates
Chengbiao Yang et al.
DOI: 10.1039/C3OB40969D

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Antigenic sugars identified for Chagas disease

Scientists in the US and Spain have synthesised the combinations of sugars from the surface of the Chagas disease parasite that trigger the human immune response to it. This could help establish better diagnostic tests for the disease, and even a vaccine.

The triatomine beetles that transmit Chagas disease are known as kissing bugs because they tend to feed on people’s faces

The triatomine beetles that transmit Chagas disease are known as kissing bugs because they tend to feed on people’s faces

Chagas disease is caused by the parasite Trypanosoma cruzi. The parasite is transmitted by contaminated food, blood transfusions and blood sucking beetles commonly known as kissing bugs. After a phase of acute local infection, the disease becomes chronic and can eventually lead to life-threatening heart and digestive system disorders. Already endemic in Latin America, Chagas disease is also becoming more of a health issue in Europe and the US with blood banks now screening for it.

Currently, Chagas diagnosis involves spotting the parasite during microscopic investigation of blood samples or checking to see if antibodies in blood samples of infected patients bind to a lysate of Chagas parasites, but these tests are not very sensitive. As treatment is only effective at the acute stage of infection, better diagnostics are highly desirable.

The surface of the parasite is garnished with unusual sugars, but until now it has not been clear which ones elicit antibodies to the parasite. Sugar chemist Katja Michael and glycobiologist Igor Almeida from the University of Texas at El Paso and colleagues have synthesised combinations of α-galactose sugars from the Chagas parasites’ surface to solve the mystery. Sera of blood samples from infected patients were added to fluorescent immunoassays of the different sugar combinations. The assay revealed the disaccharide Galα(1,3)–Galβ as the immunodominant glycotope on the parasite’s cell surface.

Read the full article in Chemistry World

Potential use of synthetic α-galactosyl-containing glycotopes of the parasite Trypanosoma cruzi as diagnostic antigens for Chagas disease
R A Ashmus et al
Org. Biomol. Chem., 2013, Advance Article
DOI: 10.1039/C3OB40887F

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A chemical approach to biological antifreeze

Scientists in New Zealand and the US have synthesised a protein that helps inhibit ice crystal growth in Antarctic fish.

Antifreezes are chemical additives used to lower the freezing point of water. While ethylene glycol is widely used in motor vehicles, it is too toxic for use in foodstuffs. Antifreeze proteins are a non-toxic alternative and are currently added to some brands of ice cream to improve the ice cream’s texture by controlling the growth of ice crystals.

A 132 amino acid protein called antifreeze potentiating protein (AFPP) was recently identified in Antarctic fish. AFPP enhances the antifreeze effects of known antifreeze glycoproteins by binding to ice crystals, but is difficult to isolate and purify in quantities sufficient for more widespread use. A chemical synthesis of AFPP would enable the large-scale production of AFPP. It would also give researchers a way to make labelled versions of AFPP for further studies

Margaret Brimble and Clive Evans at the University of Auckland, and their co-workers, have devised a convergent chemical strategy to prepare AFPP. A solubilising tag to improve the handling and purification of intermediate peptides was used in the synthesis as AFPP is not very soluble in aqueous solution and prone to aggregation.

Read the full story on Chemistry World

Chemical synthesis of a masked analogue of the fish antifreeze potentiating protein (AFPP)
Sung-Hyun Yang, Joanna M. Wojnar, Paul W. R. Harris, Arthur L. DeVries, Clive W. Evansd and Margaret A. Brimble
DOI: 10.1039/c3ob41066h

Free to access for 6 weeks!

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Never shut down another person’s ideas

Vy Dong is a professor at the University of California at Irvine, US. Her group investigates better tools for organic synthesis, including new reagents, catalysts and strategies.

What inspired you to study science?

During university, I was interested in both the sciences and the humanities, and so I took an advanced English course. After long discussions on different ways to interpret the story, I was frustrated because the instructor would never say whose interpretation was the right one. This frustration solidified that science suited me better, because you can come up with creative proposals and there’s this opportunity to test them and see if they’re valid or not.

What led you to chemistry in particular?

Taking Larry Overman’s sophomore organic chemistry class at the University of California at Irvine was a big turning point for me. Before that I was studying a major between biology and social science, called applied ecology. Larry is an amazing teacher.

A focus of your research is catalysis – could you tell us about a key project you’re running right now in your lab and why you find catalysis so attractive?

One of the major projects in my group right now is focused on catalytic hydroacylation. We want to find ways to selectively activate aldehyde C–H bonds to synthesise ketones, esters and amides. Our goal is to use this C–H activation strategy as a unified approach to all sorts of different heterocycles and polyketides and be able to do this in a way that is regio-, enantio- and chemo-selective. There’s something very attractive about catalysis – you can get things to transform that normally wouldn’t by adding a bit of this magical powder.  

What would you say is the major challenge in catalysis?

For my group, the challenge is: how do we bridge that gap from finding something that is novel in reactivity to something that’s going to be wide in applications? It is a difficult challenge, but inspiring to see how catalytic transformations, like metathesis or hydrogenation or cross-coupling, have changed the way people make molecules.

Where do you look for ideas?

I wish there was a journal we could just flip through. Initially I worried that coming up with ideas was impossible, but new ideas pop up all the time through interactions with my students. My students will suggest something and I’ll suggest something else and this going back and forth is what generates and refines our ideas. It’s important for both sides to never shut down the other person’s ideas, but rather build upon them.

One of my students suggested an experiment and instead of saying ‘that’s known with a different catalyst, let’s not do it,’ I said ‘sure, try it and see what happens.’ The result was not what either of us expected. Instead of saying ‘well, this result is interesting but maybe not that interesting,’ we tried to realise the potential in the result, thinking of all the possible ways that we could take it in different directions. That’s how we got started on the ketone hydroacylation project!

Read the full story on Chemistry World.

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Thalidomide teams-up with turmeric to kill myeloma cells

Cancer researchers in the US and China have combined the turmeric spice pigment curcumin and the drug thalidomide to create hybrid compounds that can kill multiple myeloma cells.

curcumin-thalidomide-hybrid-structure_300Multiple myeloma is the second most common type of blood cancer, killing 20% of affected patients each year. The drug thalidomide, banned after causing birth defects when given during pregnancy in the 1950s, was recently rediscovered and approved for the treatment of multiple myeloma. Thalidomide works by disturbing the microenvironment of tumour cells in bone marrow. However, it disintegrates in the body. Curcumin, a yellow pigment from the common spice turmeric, is also active against cancers, including myeloma, but is limited by its poor water solubility.

Shijun Zhang at Virginia Commonwealth University, US, and colleagues, have synthesised compounds combining structural features from both thalidomide and curcumin. ‘The hybrids have enhanced solubility, and higher toxicity against myeloma cells than curcumin, thalidomide, or a mixture of both,’ explains Zhang, ‘so our design rational is going in the right direction.’ Zhang says the hybrids kill myeloma cells through combined mechanisms of action that include the generation of reactive oxygen species and cell cycle inhibition.

Read the full story on Chemistry World.

K Liu et al, Org. Biomol. Chem., 2013, DOI: 10.1039/c3ob40595h

Free to access for 4 weeks!

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