Friday, December 29, 2006

Last post of 2006

I am going to do family things for the next couple of days, so this will be the last post of this year. I left the lab early, the other two guys left as well and I can not work alone, so I am going to make my wife and kids happy.

A final top 5 of 2006:

Top 5 of discussed topics in Blogshire

1) J.J. La Clair (no explanation needed)
2) Chemblogging (no explanation needed)
3) Polonium 210 (no explanation needed)
4) Tenderbutton's death (see comments on 1, 2 and 3)
5) cooking (see for instance 'In the pipeline' and 'Dylan's collumn'; too lazy to add links)

I wish all my readers of this blog (all three of you) a great 2007 with beautiful crystals. good IC50 and nice physchem props.

Thursday, December 28, 2006

Alcohol abuse

A nice review in the Lancet : Alcohol abuse in the critically ill patient. It contains an overview of what becomes of your body when you drink too much.

Right.. They mean you will become a smelly and mentally unstable begger when you drink too much.

They give a definition of alcohol abuse.

Alcohol abuse or harmful use is defined as a pattern of drinking that leads to clinically significant physical or psychological harm within a 12 month period.
The maximum drinking limit for healthy men aged up to 65 years is no more than four drinks in a day, and no more than 14 drinks in a week. For women and healthy men aged over 65 years, the maximum drinking limit is no more than three drinks a day, and no more than 7 drinks in a week.

I am glad Christmas is only two day, and New year's eve only one evening. It opened my eyes, so from now on I will drink only 14 pints of cask strength single malt a week.

Friday, December 22, 2006

Christmas cactus

In addidtion to the previous post I decided to run another word through the sciencedirect search engine.

Nice to have this in a Bioorg. Med. Chem. article in December.

Tuesday, December 19, 2006

Article Titles Analysis

ATA (Article Titles Analysis) may become a new way to discover trends in science. Article titles of Tetrahedron and Tettrahedron Letters, for instance, give a nice view on how things are going on in synthetic organic chemistry. The frequency of occurence of certain words in titles reflects trends in chemistry. Words in article titles of Tetrahedron and Tet. Lett. of the last 6 years were counted.

How good was the chemistry in 2006?

The greatest thing is that the efficiency of the chemistry is increasing every year.

Efficient chemistry was done almost 300 times in 2006. It almost doubled in 6 years!

Although the efficiency is increasing rapidly, it did not make the chemistry more convenient and not easier. The versatility has been quite steady.

If I were in management I would say that a target for 2007 is to try to translate the obtained efficiancy into more convenient and easy synthesis.

What was done exactly in 2006?

As we can see the best years for metathesis are over, and Suzuki-coupling managed to recover from the 2003 Suzuki-depression and is now taking a lead.

In what medium is the chemistry done?

Apparently conventional solvents are losing terrain. The ionic-liquid mania is still going on, and aqueous and solvent-free reations are increasing rapidly as well. The green guys seem to be winning.

Conclusion: Efficient Suzuki-couplings were done in an environmental friendly manner but it did not make life easier.

Saturday, December 16, 2006


This is not a picture of moonshine on the surface of juptier. It is my round-bottom flask.

(click pic's for large pic's)

I had to clean my glassware because some amoebic sediment was having a party in my flask. The glassware had been in my shed for three weeks.

I found other weird things there...

No, it is not my haute cuisine insect soup. It is my oil bath.

Three weeks ago I distilled the last batch for this year. It takes some time before you can get drunk.

Starting with inexpensive and readily available sugar, the show begins.

You need : from left to right:
citric acid, yeast, yeast nutrient (diammonium phosphate), and sometimes activated coal.

The sugar is cooked in water with citric acid to hydrolyse the glycosidic bond of sucrose turning it into invert sugar. The monosaccharides are fermented much better than the disaccharides. Oxygen rich water is added together with the nutrients and the yeast. The yeast starts to multiply. Ofcourse you use something like TurboYeast to obtain as much ethanol as possible (up to 18% can be reached using these types of yeast). The fermentation is done under anaerobic conditions.

People say : "It is dangerous, watch out for the methanol. If you drink it, you will not be able to read the newspaper anymore!!" That is bullshit, methanol can not be formed when using pure sugar. It can be formed when fermenting fruit (pectins), but with a good still you can remove it with the the first fractions of the distillation.

With the TurboYeast it takes about two weeks to complete the fermentation. Now in December it is too cold here to do this. I usually ferment 10 litres every time. After fermentation you decantate the solution to remove the dead yeast and the first destillation is done. I have a three litre flask so I have to distill 4 times. (I do this in about 4 times 50 minutes). The 10 litres give about 1.7 litre of 70% ethanol after the first distillation. Sometimes you have a bit of nasty sulphur smell in it. This is often occuring when the yeast was too old, or the fermentation was left for too long. You can remove the nasty smell with activated coal (or by using a real copper still).

The purity of the ethanol is meassured with a density meter.

Let it float in the distillate, and read the percentage.

This one is only for ethanol water mixtures, so it will not work for wine wich has other ingredients. The water ethanol mixture can be diluted to about 40% to have a nasty shot of vodka.

I do not like vodka, so I flavour the ethanol with herbs. Crush the herbs in a mortar like an alchemist, and let it stand in the ethanol for a week.

I like (from left to right) : juniper berry, rosemary, tyme, nutmeg and pepper.

After a week the herbs are filtered out and the ethanol is distilled again. I usually get 1.4 litres 80% flavoured ethanol. I dilute this to 40% to have 2.8 litres of nice jenever. Optionally you can mature the jenever on roasted chips of oak wood.

This will give the jenever a nice color and an extra flavour.

The 2.8 litre of korenwijn-like spirit will cost you about $50 in a shop. The used ingredients for my 2.8 litre cost about $3 and an additional $5 for the butane/propane mixture to heat my oil bath. All the stuff can be bought easily. Biggest problem is the lab-glassware. You can make a still yourself from an old copper boiler, or milk can. Or search for real lab glassware on E-bay. You can not walk out of your lab with a 3 litre round bottom flask under your arm, I presume (you might want to keep your job).

I have 9 bottles of this stuff right now, so I hope I can get through the winter. In april the show can begin again

Tuesday, December 12, 2006

Top 5 scandals in medicine and chemistry

1) Henk Buck/Jaap Goudsmit

Using the antisense method with phosphate-methylated DNA, Buck and Goudsmit claimed to have found a cure for AIDS and published their findings in a Science article. They held a press conference for the media to present their findings. The massive media attention made the scandal only worse. Colleagues discovered errors in their research, and it turned out that the phosphate-methylated DNA was not a stable compound, and the used samples could not have been pure.

It is said that Buck was a stubborn man who did not tolerate any resistance. His university did not immediately investigate the allegations of Buck’s colleagues, so the colleagues decided to go to the media with the supposed fraud in order to diminish the public optimism in the fight against AIDS. After this media attention the whole case was investigated. Buck was fired and Goudsmit rebuked.

2) Elias A. K. Alsabti

An Iraqi cancer specialist who published about 60 plagiarized papers in obscure journals with probably non-existing colleagues in order to boost his CV. While working in the USA it became clear that he had no real scientific knowledge. Eventually it seemed to be that his whole career was falsified.

3) Vijay Soman/Philip Felig

As peer reviewers for ‘The New England Journal of Medicine’ they rejected an article by Helena Wachslicht-Rodbard. They copied the paper with their own names on it and submitted it for publication in ‘The American Journal of Medicine’. Unfortunately for them, Helena Wachslicht-Rodbard was asked to peer review her own (stolen) article.

4) Jacques Benveniste

Benveniste published a paper in Nature that a homeopathically diluted solution of antibodies could activate white blood cells by the so-called ‘memory of water’. Benveniste failed in reproducing the results when John Maddox and James Randi investigated the work in Benveniste's lab.

Benveniste also claimed that the information that is stored by the ‘memory water’ could be transmitted over the internet or telephone lines. Benveniste was awarded the IgNobel prize twice.

5) Guido Zadel

He published a paper 'Enantioselective Reactions in a Static Magnetic Field‘ in Angewandte Chemie in 1994. It turned out that his results were falsified. Even results of his colleagues were falsified by replacement of samples. The results were part of his dissertation, and his PhD was eventually withdrawn.

Elena Ceauşescu

A few years ago, before I got into industry, I was relaxing in the university library. Tired of defending my glassware and fighting over the last 100 ml of dichloromethane I usually went there to read Chemische Berichte of 1897 or the first issue of Nature. This time I found a book called: ‘Stereospecific Polymerization of Isoprene’ (1982). It caught my attention because of the name of the writer; Elena Ceauşescu.

I didn’t read the book (polymer chemistry is no expertise of mine), but I saw the book came from Romania, and was indeed a book by THE Elena Ceauşescu. I rembered seeing her execution on TV a few years before. Inside the books of the library were lists of all people who borrowed it. This list was empty.

Fascinated by this historic document I searched the catalog and found out that almost all European university libraries had a copy of the book. It turned out that Ceauşescu had sent the book herself to the libraries.

Elena Ceauşescu was seeking for status, and with her husband’s influence she was able to obtain it. Her PhD in chemistry is probably false. It is disputed that she wrote the book herself, and it is said that she didn’t have the intellectual capabilities to obtain a PhD.

Scifinder gives 90 hits on her name. Starting with a patent, filed in 1964 with her name on the second place.

In 1965 the Romanian communist leader Gheorghe Gheorghiu-Dej died, and Nicolae Ceauşescu came to power. After that point, all other 89 patents and publications (Materiale Plastice/Revue Roumaine de Chimie) name Elena as the first author. Finally she had obtained a status as a scientist, and a status as the most hated person in Romania as well.

The last book she published (Dostizheniia v khimii i tekhnologii polimerov) appeared in 1988. A year later she probably sang : "Last Christmas".

Monday, December 11, 2006

Top 5 : Executed Chemists

1) Antoine Lavoisier
Guillotined on May 8 1794 because of his job as a tax collector.

2) Elena Ceauşescu
Shot with a sub-machine-gun on December 25 1989, after the fall of her husband’s dictatorship in Romania.

3) Masami Tsuchiya
Sentenced to death on Januari 30 2004 because of his role in the Sarin gas attack on the Tokyo subway by Aum Shinrikyo.

4) Bruno Tesch
Executed on 16 May 1946 because of the production of Zyklon B for 'The Third Reich'.

5) Ernst Cohen
Executed (murdered) March 5 1944 in the gas chamber of Auschwitz.

Thursday, December 7, 2006

Evolution versus Creation

Nature published a news article about an open letter from Polish scientists to protest against an anti-evolution campaign launched by the creationists of the League of Polish Families (LPR).
The Polish scientific community is concerned that this will effect biology teaching in schools through LPR-leader and Polish minister of education Roman Giertych and his father and LPR member of the European Parlaiment Maciej Giertych, the latter holds a PhD in tree physiology.

The article states that “neither Roman nor Maciej responded to Nature’s request for comment.”
Maciej Giertych however did comment in a later issue with the usual evolution criticism. Maciej Giertych’s correspondence received lot of criticism from the scientific community. His arguments are called pseudoscientific, and other arguments are said to be untrue. Several people state that Nature should not have published Maciej Giertych’s correspondence.

It is a difficult problem I think. On one hand Giertych should be able to comment on an article that mentions him, even if his comment contains scientific errors. On the other hand : Should Nature provide Giertych an audience to tell his pseudoscientific views that have political implications as well?

I don not know…
Pseudoscience can evolve into science. Alchemy became chemistry, although I can not see where this anti-evolution must lead to.

The Giertych’s contemptuous homophobic and aniti-Semitic opinion makes me think that you should ignore those guys. Unfortunately the Giertych-clan can not be ignored because of the positions they have.

My conclusion is that I hate it when science, religion and politics are mingling. It goes well when they live together. You can prove that the earth is not the centre of the universe while being a devout Christian. It goes wrong when the church and state interfere in your discovery, then you are silenced and can only mumble :”Eppur si muove”.

I think that both evolution and creation have to be taught in school, which of the theories is supported is up to the pupil. Both theories are important because of their value. Whether is a cultural, historic, religious or scientific value is not important for curriculum inclusion. Politics should not determine what is believed to be true.

Monday, December 4, 2006

Stupid things to do as a (Med.) Chemist

- Synthesize a reference compound and discover afterwards that senior management decided to stop the project without telling you.

- Be a sales representative for Pfizer.

- Publish your optimized Suzuki reaction in water and tell the chemistry is oh so green, and hide the experimental procedure with the 5 litres dichloromethane extraction as a note between the references.

- Try to explain the biologist why the unreliable 6 step synthesis of the compound with 5 chiral centres takes much more time than the straightforward 8 step synthesis of another symmetrical compound.

- Explain your peasant neighbor what you do for a living.

- Criticize the senior management.

- Be honest about your trust in the validation of your target.

- After finishing a successful project, tell the boss that a project was much easier than expected.

Saturday, November 25, 2006

Spinning side band spectrometry

It is very frustrating when machines are down. Sometimes you can see perfomance decline over a period, and it has to be really bad before it is fixed.

We had a problem with our NMR this week. The magnetic field homogeneity got worse within a few days resulting in the same spectrum for all our compounds : 9-0 ppm, multiplet, all H's. One TMS peak became three, and after a week we couldn't count the number of TMS peaks anymore.
We are so lucky it got so bad. The manufacturer came yesterday and fixed the problem after a day kicking the magnets and a few hours of shimming.

Wednesday, November 22, 2006

Top 5 chemistry relics

Draft for the first version of the periodic table, February 17, 1869
Oesper Collection, University of Cincinnati, USA

Models of assymmetric molecules, 1874
Museum Boerhaave in Leiden, the Netherlands

"Photo 51" Sodium deoxyribose nucleate from calf thymus, Structure B, May 2, 1952
Oregon State University's Special Collections, USA

Mercury gasometer, used to identify chemical properties of oxygen, 1774
Musée des arts et métiers - Cnam, Paris, France

Original botlle of mauve dye, 1856
Science Museum London, UK
This sample is most likely not the real first sample; "it cannot be earlier than 1862"

Tuesday, November 21, 2006

For the kids.

For the kids there are some cuddly toys available here. E-coli, Hepatitis, Black Death or one of these. Very nice for your kids to have in bed. Sweet dreams.

Monday, November 20, 2006

Saturday, November 18, 2006

Some aqueous solution

The most horrible aqueous solution we have is the dark rubbish from some dispensing robot. People refer to this solution as coffee. Lack of something decent makes me drink this stuff about a litre a day resulting in headaches and trembling limbs. Trying to find out what it is that I poison myself with, I did a LCMS analysis of it.

click pic for larger view

It turned out that caffeine gave a dominant peak in the chromatogram, and was the only peak with a clear MS-spectrum.

It will not surprise me if our boss just wants to make sure we work as fast as possible.

Friday, November 17, 2006

Kill your project ASAP

This month Nature Reviews Drug Discovery contains an article about Tufts CSDD Impact Report. Bayer, AstraZeneca, Allergan, Boehringer Ingelheim and Merck turn out to be the speed-demons of pharmaceutical industry.

"These five companies, according to the report "deliver as much as a 17-month speed advantage over average performers"."

The reason is clear why other are so slow.

"Decisions still tend to be made at the highest possible level, which means decision-makers have less insight into what people are working on. Project teams go to the decision-makers fighting for their compounds as much as possible, and are reluctant to give up on their project, in the hope that a project will succeed through perseverance. This makes it easy for projects to run beyond the point where the team knows they are not going to work."

Wow.. What a conclusion… We all knew that already. This is how it works in all industries, and in politics as well.

Thursday, November 16, 2006

Who is who in chemicals and labware

Could not find H. Vigreux, E.W. Dean and D. D. Stark

Alfred Nobel / Chester Fischer / John Baker / Irénée du Pont / Gilbert Lewis
Johannes Brønsted / Hugo Schiff / Sir Geoffrey Wilkinson / Louis Fieser / Paul Ehrlich / Erhard Mettler
Richard Perkin / Charles Elmer / Russel Varian / Warren Gilson / Walter Büchi
Friedrich Beilstein / Sir William Perkin / Arnold Beckman / Robert Bunsen / Justus von Liebig

Georg Büchner / Wilhelm Schlenk / Emil Erlenmeyer / Sir James Dewar / Ludwig Rainer Claisen

Wednesday, November 15, 2006

Mr. Vigreux

Henri Vigreux gave his name to a piece of glassware, biographic facts are unfortunately hard to find.. Vigreux, a glassblowing chef from Paris, published a book about their instruments in 1920; Le soufflage du verre dans les laboratoires scientifiques et industriels
Browsing through the book I see nice equipent I would like to have in my shed to prepare my own mooshine.

Some illustration represent glassware that makes me wonder what it is used for. Unforntunately my French is far from perfect, and my fluently French speaking wife is not prepared to translate the 280 pages of instrument descriptions.

Looking at all the glassware in this book I realize how spoiled we are in industry. Specific glassware becomes a rarity on our labs. The last vigreux I touched was last year, cracking dicyclopentadiene wich was the last destillation I did as well. You have to search the whole building for a complete destillation-set on the right scale. There is some mini-scale glassware that becomes mouldy and almost starts to decompose We are so spoiled we buy dry solvents, stored under nitrogen on molsieves. Ground-glass jointless glassware can nott be found here. Reagents like diazomethane are almost prohibited, we need 523 signatures and fill in 735 forms to be allowed to use such reagents. Apart from LDA we buy everything that can be made easily, because we have the presumptuous idea that our time is more expensive than the commercial reagents. It is a miracle we are able to synthesize anything at all.

Tuesday, November 14, 2006

Who is who in pharmaceutical industry

Adolf von Baeyer/Charles Pfizer/John Smith/Mahlon Kline

Ernest Solvay /Albert Boehringer /Robert Johnson/Edward Johnson

Fritz Hoffman-La-Roche/Wallace Abbot/Eli Lilly/John Wyeth/Chobei Takeda I

William Bristol /John Myers/Edward Squibb/Emanuel Merck/Ernst Schering

in vivo pH measurement


Organic Chemistry : An Intermediate Text 2Nd Ed.
by Hoffman, Robert V.
Publication: Hoboken, N.J John Wiley & Sons, Inc. (US), 2004.