A catalyst for axial chirality

by Lars Fischer in EuCheMS 2010 Blog

Axial-chirality or atropisomerism is a very useful property as demonstrated by various chiral catalysts containing BINOL, BINAP and similar groups, but not only there. Many important natural products like e.g. the antibiotic Vancomycin are also atropisomers, which makes this property a very important aspect of stereoselective chemical synthesis. Which is extremely difficult to achieve synthetically [...]... Read more »

Sugar-Sweetened Beverages: Bane of Mankind?

by Steve Parker, M.D. in Diabetic Mediterranean Diet Blog

Over the last 30 years in the U.S., consumption of sugar-sweetened beverages (SSBs) has increased from3.9% of total calories to 9.2% (in 2001).  In that same time span, the percentage of overweight American adults increased from 47% to 66%.  The obesity percentage rose from15 to 33% of adults.  [Did the beverages cause the weight gain, or [...]... Read more »

A Biochemical Assay that May Help Predict Adolescent Suicide Risk

by Michael Long in Phased

Damir Janigro (Cleveland Clinic, United States) and coworkers have developed a biochemical assay that may help predict the risk of suicide among psychotic adolescents, enabling preventive care to be focused on those most in need of early intervention. This news feature was written on June 16, 2010.... Read more »

Reflections on the Gulf Oil Spill - Conversations With My Grandpa

by Christie Wilcox in Observations of a Nerd

Yes, it would be great if we never spilled a drop of oil. No matter how hard we may try, though, the fact is that nobody is perfect, and oil spills are an inevitable consequence of our widespread use of oil. The question is, once the oil is out there, how do we clean it up? Perhaps my grandfather put it best, when I asked him what he thought about how BP and the US is responding to the spill.

"They're friggin' idiots."... Read more »

The origin of life cannot escape basic organic chemistry

by The Curious Wavefunction in The Curious Wavefunction

One of the key challenges facing any theories of the molecular origins of life concerns the synthesis, stability polymerization and self-assembly of early life's molecular components. If you cannot explain the chemical origin of these components, you cannot really explain the origin of life. In case of life as we know it, this boils down to explaining the origin of the building blocks of living organisms, namely nucleotides and amino acids.The simplest principles and quirks of chemistry could have had an influence on how life could have evolved. A neat paper in ACS Chemical Biology offers a potential explanation based on basic organic chemistry for why a certain class of phosphorylated nucleotides formed in preference to others, even though 'conventional' organic chemistry would dictate the opposite.An anhydroarabinonucleoside has been postulated as an important potential precursor to further nucleotide synthesis. A key step is the phosphorylation of this nucleoside to yield an activated cyclic nucleoside phosphate. Having an activated molecule makes all the difference since activation primes the molecule to be attacked by further nucleophiles, thus triggering polymerization and growth.However, the phosphorylation of the arabinose nucleoside raises a fundamental question (hopefully) familiar to sophomore organic chemistry students. Why does phosphorylation take place preferentially on the secondary 3'-OH while sterically, as every student of organic chemistry knows, it should be preferred much more on the primary 5'-OH?To tackle this question, the authors get a crystal structure of the nucleoside in question. This x-ray structure shows an unusually short distance between the 2'-OH oxygen and the C2 carbon (2.7 A). Energy optimization using quantum chemical techniques surprisingly does not get rid of the short distance. Because of this proximity, the 2'-OH can undergo an internal attack on this carbon to generate a reactive intermediate, whose ring can be opened in turn by a 3'-OH phosphate to form the activated phosphate product. Now, the 5'-OH also gets phosphorylated; it's just that it cannot attack the C3 carbon of the activated intermediate the way the 2'-OH can because it's not in proximity to this carbon the way the 2'-OH is.The authors explain the short distance between the 2'-OH and the C3 carbon by postulating an interaction between the lone pair of the 2'-OH oxygen and the pi* orbital of the C2=N bond. This kind of interaction is quite familiar to organic chemists; it is invoked in the famous Burgi-Dunitz trajectory that enables nucleophilic attack on carbonyl carbons. Indeed, the authors perform a theoretical analysis that shows the angle of attack for the 2'-OH to be about a 100 degrees, close enough to the Burgi-Dunitz trajectory.This is a classic case of there being two competing pathways in chemistry, one of which is preferred to the other because of a subsequent low-energy route that can be traversed. It's a common theme in chemistry and biochemistry and illustrates how otherwise counter-intuitive reactions can be accelerated by putting them at the top of the right energy cliffs. No matter how complex life may be, it still cannot get around the basic laws of organic chemistry. Score one for thermodynamics.Choudhary, A., Kamer, K., Powner, M., Sutherland, J., & Raines, R. (2010). A Stereoelectronic Effect in Prebiotic Nucleotide Synthesis ACS Chemical Biology DOI: 10.1021/cb100093g... Read more »

“As Close to a ‘Polluting Plant’ As One Can Find”

by Promega Corporation in Promega Connections

Far Eastern vines Run from the clay banks they are Supposed to keep from eroding. Up telephone poles, Which rear, half out of leafage As though they would shriek, Like things smothered by their own Green, mindless, unkillable ghosts. In Georgia, the legend says That you must close your windows At night to keep it [...]... Read more »

by Lars Fischer in EuCheMS 2010 Blog

With increasing demand for effective separation of small-molecule gases – think of carbon caption and storage – there has been a lot of research recently into strategies and materials suitable for those applications. The traditional way to separate gases like nitrogen, oxygen or carbon dioxide is to freeze them out one by one, which is [...]... Read more »

Towards a Charge-Shift Bond with a Presumed Inert Atom

by Michael Long in Phased

Henry Rzepa (Imperial College London) has presented theoretical investigations which may lead to the synthesis of rigorously provable bonds to helium, an atom commonly thought to be inert. This news feature was written on June 6, 2010.... Read more »

The smell of baking bread: Entity of the Month

by Duncan Hull in O'Really?

Release 69 of Chemical Entities of Biological Interest (ChEBI) is now available, with 584,456 total entities, of which 21,369 are fully annotated to three star level. This months Entity of the Month is the smell of baking bread, or more precisely 6-acetyl-2,3,4,5-tetrahydropyridine. The text below is reproduced from the ChEBI website where data is available [...]... Read more »

A Flexible Zinc-Carbon Battery: Towards Cheap Intelligent Clothing

by Michael Long in Phased

Pritesh Hiralal (University of Cambridge, United Kingdom) and coworkers have worked towards incorporating cheap batteries directly into clothing. This news feature was written on June 2, 2010.... Read more »

Amino acid crystallisation and the origin of life

by Lars Fischer in EuCheMS 2010 Blog

Recently I came across a number of attempts to explain the “handedness” of life – the fact that proteins consist only of L-amino acids – by the crystallization behavior of amino acids. The general idea is that something that happens at the transition between solution and crystal that favors one of the enantiomers over the [...]... Read more »

Synthesisng Soufflés

by Akshat Rathi in Contemplation

Why does a soufflé rise so much? How can you make the perfect soft boiled egg? Why should we not store raspberries in a copper vessel? Akshat Rathi investigates the science that can answer these questions. Continue reading →... Read more »

Pharmacological Interrogation of Individual Cells

by Michael Long in Phased

Aldo Jesorka (Chalmers University of Technology, Sweden) and coworkers have developed a micropipette that can quantitatively probe drug action against individual cells, in a reversible manner, without perturbing neighboring cells. This news feature was written on May 29, 2010.... Read more »

Ballistics experts of the bug world

by Katie Kline in EcoTone

Meet the ballistics experts of the bug world: A quick draw beetle that fires volatile liquids with the pulse of a Tommy Gun, aphids that self-combust at the threat of a predator and a double-pistoled worm that sprays its victim with streams of goo. Of course, these insects are not the only invertebrates carrying chemical artillery—bees are maybe the most famous projectile-launching bugs around. The below insects, however, give a unique look into chemical warfare on a small scale.

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A shot in the arm for antimalarial drug discovery?

by The Curious Wavefunction in The Curious Wavefunction

While heart disease, cancer and Alzheimer's continue to grab the headlines, malaria and tuberculosis continue to quietly do their deadly work behind the scenes. Diseases that disproportionately affect sub-Saharan Africa are not exactly priorities for drug companies. But they pose a tremendous unmet need. Especially malaria, which kills an unbelievable 800,000 people every year, has fought back against almost every traditional drug. The fight against the disease has boiled down to one class of drugs- the artemisinins. If the parasite develops resistance against these, nobody knows how fast and wide it will spread.Since pharma companies often get bad press for neglecting....neglected diseases, this makes the duo of papers in this week's issue of Nature especially impressive. The papers talk about GSK collaborating with a host of academic laboratories to discover literally hundreds of hits against malaria through phenotypic screening. The sheer multidisciplinary effort put into this endeavor is laudable. Phenotypic screening is an effective method for drug discovery since it does not care about the target of a drug, at least in the beginning. It's a more top down approach that complements bottom-up rational drug design. The goal is to simply watch out for a particular kind of response, which could be anything from fluorescence to cell shrinkage. In this case it was 80% inhibition of growth of the parasite in the asexual stage in red blood cells. Target identification can come later.The company screened its proprietary collection of about 2 million compounds. The compound library was chosen for diversity of scaffolds and novel chemotypes. The assay looked for 80% inhibition of the P. falciparum parasite, and came up with hundreds of diverse compounds. The scientists seemed to have taken due care to minimize false positives. They sought to eliminate promiscuous, lipophilic compounds from the list. They also screened their compounds against well known targets and processes that the malarial parasite exploits to subdue its host. One of these was particularly eye-opening for me; apparently, the insidious little weasel can hack up the amino acids from hemoglobin molecules in the host to assemble its own proteins. Now that's stealth for you. More interestingly, the group then screened the selected molecules against seven novel malarial targets and found encouraging inhibition profiles against these targets. Infectious disease are best treated when you can hit the causative agent in multiple places. Paucity of targets has especially been an issue for malaria and TB, and these chemotypes along with their suggested targets provide promising leads. As a final act, the first paper co-authored by Guiguemde et al. also demonstrates favorable pharmacokinetic properties for one of their hits.Especially interesting is the report in the second paper authored by Gamo et al. where the authors follow a similar procedure but discover that the novel target list for the purported antimalarial candidates is enriched in kinases. They take due care to investigate that this enrichment is not a chance enrichment. Unlike the human genome which has about 500 kinases, the malarial genome has about 80. But finding kinases among the targets of these novel chemotypes has rich implications, since kinases have already been intensely investigated, the targets are well-understood and there are literally thousands of kinase inhibitors out there waiting to be tested. Testing kinase inhibitors against malaria would open up a whole new chapter for antimalarial drug discovery.Finally, and this is the kicker most talked about, GSK has made the entire list of hits freely available to the public. This is a very laudable act. In an age where corporations are routinely derided for their emphasis on secrecy and profit-making, such a decision should drive home the good work that corporations can potentially do. It also underscores the tremendous opportunities for drug discovery against neglected diseases gained from academic-corporate collaboration. While it remains to be seen how many of these promising candidates become bona fide drugs, it provides many promising starting points for further efforts. Malaria is about as insidious a disease as you can have, lurking in the shadows and waiting to pounce on you. The more the hands that try to squeeze its neck, the better.Guiguemde, W., Shelat, A., Bouck, D., Duffy, S., Crowther, G., Davis, P., Smithson, D., Connelly, M., Clark, J., Zhu, F., Jiménez-Díaz, M., Martinez, M., Wilson, E., Tripathi, A., Gut, J., Sharlow, E., Bathurst, I., Mazouni, F., Fowble, J., Forquer, I., McGinley, P., Castro, S., Angulo-Barturen, I., Ferrer, S., Rosenthal, P., DeRisi, J., Sullivan, D., Lazo, J., Roos, D., Riscoe, M., Phillips, M., Rathod, P., Van Voorhis, W., Avery, V., & Guy, R. (2010). Chemical genetics of Plasmodium falciparum Nature, 465 (7296), 311-315 DOI: 10.1038/nature09099Gamo, F., Sanz, L., Vidal, J., de Cozar, C., Alvarez, E., Lavandera, J., Vanderwall, D., Green, D., Kumar, V., Hasan, S., Brown, J., Peishoff, C., Cardon, L., & Garcia-Bustos, J. (2010). Thousands of chemical starting points for antimalarial lead identification Nature, 465 (7296), 305-310 DOI: 10.1038/nature09107... Read more »

The amazing spider silk

by Lars Fischer in EuCheMS 2010 Blog

Even if you don’t follow materials research closely you may have come across the amazing properties of spider silk. The stuff is stronger than steel, yet more elastic than most artificial fibres, despite being made of proteins only. It owes its remarkable strength to hydrogen bonds and its microstructure of amorphous and crystalline domains. But [...]... Read more »

A Beneficial Effect of Hurricanes Katrina and Rita

by Michael Long in Phased

Howard Mielke (Tulane University, United States) and coworkers have shown that Hurricanes Katrina and Rita dramatically reduced the amount of lead in New Orleans soil, and consequently in the blood of local children. This news feature was written on May 24, 2010.... Read more »

Brazil Eucalyptus Laboratory: Modelling Productivity

by Gus in EUCALYPTOLOGICS: Information Resources on Sustainable Eucalyptus Cultivation Around the World

Eucalyptus Ecology & Environmental Sustainability : it is about Science

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Probing the Biology of Cell-To-Cell Variability

by Michael Long in Phased

Andreas Schmid (Leibniz-Institut fur Analytische Wissenschaften and Technische Universitat Dortmund, Germany) and coworkers have reviewed progress and future challenges associated with interrogating single cells to extract information that is typically lost in the average behavior of many cells. This news feature was written on May 15, 2010.... Read more »