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Moon formed by nuclear explosion

20 May 2013 - It is true.

My favorite Dutch newspaper (NRC) writes about it and the scientists are Dutch so it has to be true. In the most recent edition of the journal Chemical Geology (we temporarily lift the Elsevier ban) Wim van Westrenen et al. explain that our moon was formed not by collision of Earth with an extraterrestrial body but by a nuclear explosion somewhere at Earth's core-mantle boundary (DOI). In the early development of Earth when the crust began to cool, heavy elements such as uranium collected deeper in the core at the so-called D-layer. Impact of a small planetoid could have triggered nuclear fission. One of the main selling points for the theory is the identical isotopic composition of Earth and Moon for several light elements and heavy elements. Georeactors are also nothing new.
From the NRC article it becomes clear that van Westrenen had a hard time getting his work published. Thus far he had only written about it in the popular press. Even in the published article the explosive thesis is somewhat buried, you have to get to the second part of the abstract for the nuclear stuff.

The tetracycline challenge

18 May 2013 - Industrial chemistry

In what must be the single most important organic chemistry journal, each issue of Organic Process Research & Development features brave organic chemists doing brave organic chemistry on kilogram scale with chemicals that really matter. Take the guys from Tetraphase Pharmaceuticals who report on a grand-scale synthesis of a fluorinated tetracycline in the most recent issue (DOI) . It will come as no surprise the mission on the whole was a success but more interestingly is it to read about the setbacks and failures encountered on the way. That is what the journal is good at.
In this tetracycline story several challenges stood out. A simple Dieckmann condensation proved difficult because successful deprotonation in step one was found to depend on the quality of the particular batch of n-butyllithium. Remarkably in a trial with different BuLi batches the batch with the most solid floating around was most effective. This on account of LiCl present. Addition of Et3N.HCl neutralised the effect.
Next the scheme required a tert-butyldimethylsilyl group deprotection and efforts were made to have HF replaced by a more homonid-friendly alternative. Alas, many were tried (trifluoroacetic acid, p-toluenesulfonic acid, HF-pyridine, TBAF) but all failed due to non-performing conversion or purity. The HF had to stay.
Then more issues with commercial grade chemicals and consistency. How hard can it be to supply HCl/methanol with a consistent molality? Tetraphase's supplier apparently was not up to the job but it mattered greatly because not concentrated enough triggered premature precipitation of an intermediate in the next hydrogenolysis. As a workaround the team made their own HCl/MeOH from the concentrated acid.

Troubles not yet over but with the finish line in sight one of the final steps was an acid chloride acylation to a tetracycline intermediate with no less than 6 potential acylation anchors. Solubility of the reactant was found to depend on the reaction scale (how?) but by a stroke of luck at just the right pH the overacylated sites were reversed to the original state.

Final result: half a kilo of eravacycline ready for the next clinical trial.

Nanotube meets Microwave oven

16 May 2013 - Tweaking

The combination of nanotubes and microwaves is irresistible. Scientists have been analysing, functionalising and destroying nanotubes inside a microwave for a long time. Actually synthesising them using microwaves has attracted less attention. In 2011 a US collective with first author Liu ( DOI) introduced a poptube method for fast synthesis of nantubes with microwave irradiation. All that was required was a mixture of ferrocene and a certain conductive polymer.

In a recent development another US team with first author Nie discovered that the polymer can be replaced by a single nanotube as a kind of seed ( DOI). That is good news because the Nie team felt that synthesising the required polymer was too complex anyway. If the Nie team has tried to reproduce the Liu effort remains unclear but with the new nanotubes-create-more-nanotubes scheme it did not really have to.

A single 3-4 cm nanotube strand is placed in a vial together with 100 mg of ferrocene. Inside the microwave oven heavy sparking originates from the tip of the strand and temperatures reach up to 1000°C finally resulting in a black soot. Iron as nanoparticles catalyse the conversion. 40% yield with just 20 seconds of exposure.

This blog is not convinced though that it really requires a nanotube strand to get the job done. Already in 2003 Hong et al. reported that nanotubes could be synthesised from any surface be it carbon black, silica powder or teflon (DOI).

Alkanes reinvented

11 May 2013 - Green chemistry

Nonane synthesis Sutton 2013  The gradual replacement of fossil fuels by biofuels requires the reinvention of many chemicals that now also rely on fossil fuel feedstock. Sutton et al. point out that the conversion of highly functionalised biomaterials to typically non-functionalized hydrocarbons requires special chemistry. They report the synthesis of nonane from hydroxymethylfurfural and acetone as a proof of concept (DOI).

Step 1 is a chain extension and an aldol reaction, step 2 is a one-pot reaction and a combination of hydrogenation and deoxygenation. Challenge encountered: the furan ring has open before furan hydogenation because that leads to a further non-reactive product.

Amidation via borate esters

09 May 2013 - Organic chemistry

Amidation Lanigan 2013  Lanigan et al. report a new reagent for coupling an amine with a carboxylic acid to form an amide (DOI). The reagent is the borate ester of trifluoroethanol B(OCH2CF3)3 for which they offer a new recipe starting from boron trioxide.
The yield of the reaction with boron trioxide alone is poor, chirality is retained with protected amino acids.

Acrylonitrile spill hits Belgian town

07 May 2013 - Risk assessment

An ongoing chemical disaster in Belgium is getting people worried. Each day a train loaded with acrylonitrile makes a journey from the Dutch port of Rotterdam to the Belgian city of Ghent and its port. On May 4 one of those trains derailed (cause: overspeeding) just outside the Belgian town of Wetteren and caught fire (NOS News BBC News). This fire was quickly dealt with but the disaster had yet to start.

Large amounts of acrylonitrile together with partial-combustion product hydrogen cyanide made it's way into the town's sewage system partly due to the use of water in the fire fighting operation. But then toxic fumes made it back up into local houses causing the death of one resident and his dog. Ironically in the event of chemical disasters, authorities (in this part of the world) advise and expect residents to stay indoors with the windows shut.

Now three days later lethal concentrations of hydrogen cyanide still come up from the sewer and a large evacuation is anticipated (De Morgen). The arrival of rain does not help.

Update 08-05-2013: Evacuation not needed after all.

Exploring chemical space

06 May 2013 - Boldly go ... yeah yeah we get it

unexplored chemical space.PNGAn intriguing map as published by Virshup et al. in JACS (DOI). But what is it? The Virshup article describes an algorithm for generating a universal library of small molecules optimised for diversity. Apparently a lot of chemical space is left unexplored. This blog made an honest attempt at fleshing out the details but the article proved stubborn.
The take-off point is surprisingly simple: The algorithm starts with just two molecules: benzene and cyclohexane. In each new generation atoms are then substituted, bonds broken or formed and molecules joined as fragments. The new molecular set is then filtered for things like synthetic feasibility, conformational stability and drug likeness. In addition to that, in each generation only a set of maximum diverse molecules makes it to the next round. So far so good, the final set contains 9 million very diverse molecules.
The article then describes diversity being assessed by comparing molecular topology into 40 dimensions and then converting to a vector representation. The 9 million molecules (existing or non-existing) are positioned on a grid with each section sharing some topological traits. The final thing to do then is plotting all existing molecules from lets say the Pubchem database on the same grid. It then emerges that they all appear to cluster together in a vast mountain range leaving most of the grid eerily empty. But then again the article proved stubborn.

A boy and his molecule

02 May 2013 - Movie time

Moving an atom.PNGThe new movie produced by IBM research should of course not be called "A boy and his atom" but "a boy and his molecule" because the movie was created by moving around molecules of carbon monoxide and not discrete atoms. Some complaints were logged on the youtube comments section and twitter.

On the other hand it is fascinating that this didactic flaw can be spotted by simple visual inspection.