Tuesday, October 22, 2019

The Antistatic Portal

For a change I had to leave the office, put on a lab coat and go to the lab to weigh out some compound. I had a nice fluffy freeze dried substance that had to be transferred from one vial to another. I was faced with usual static electricity problem. The easy solution is to take your plastic gloves off and hope that your compound doesn't fly around the hood when you try to transfer it. However, as often as not this will not do the trick. For the same reason the antistatic gun has been developed (see picture).
If you "shoot" your vials a couple of times this will help, sometimes, maybe. I find it a bit of a lottery whether this works even without gloves on. Which brings me to the point of this post, the Mettler Toledo™ U-shaped Ionizer Antistatic System or as I call it "The Antistatic Portal". It reminds me of the movie Stargate as it's standing there next to your balance humming with electricity (see picture below). Basically the idea is that you just move the stuff that is being weighed through the portal and voila the problem is solved without travelling to distant planets and fighting Egyptian Gods.
Pretty neat and the damn thing actually works with plastic gloves and all so I can recommend this addtion to your lab (if you can afford it). D!

Tuesday, June 26, 2018

The Disconnection Approach - Automated!

In my time as a synthetic organic chemist the most important advance in the field was definitely the introduction of searchable databases such as SciFinder and Reaxys. Life before these involved spending days on end in the library flipping though dusty tomes of chemical abstracts and Beilstein. And at the end you weren't even sure if you missed something of critical importance. The introduction of open access LC-MS and high field NMR has also had a big impact for me by speeding things up considerably. However, besides these milestones I think that I have pretty much been doing chemistry the same way >25 years. Anyway, what I am getting at is "what will the next BIG thing be?" It's been a considerable time since we had a major technical breakthrough for the synthetic organic chemist. My colleagues and I have been discussing this for more than a decade and now I think I am spotting the next big thing - Chematica! Chematica was developed by Polish scientist Grzybowski and has been around for quite a while. Basically it is a computer programme that disconnects your molecule and suggests ways for you to synthesise it. What's changed since I first heard mention of Chematica ~5 years ago is that apparently now it works the way you would like it to. Recently Grzybowski and co-workers published an impressive paper where they synthesise 8 very different and rather challenging molecules. The abstract from the paper nicely summarises the achievement:

"Multistep synthetic routes to eight structurally diverse and medicinally relevant targets were planned autonomously by the Chematica computer program, which combines expert chemical knowledge with network-search and artificial intelligence algorithms. All of the proposed syntheses were successfully executed in the laboratory and offer substantial yield improvements and cost savings over previous approaches or provide the first documented route to a given target. These results provide the long-awaited validation of a computer program in practically relevant synthetic design."

You really should read this paper. These are not simple syntheses and would have taken quite some time to come up with if at all. Now it is still early days and Chematica is only for those with deep pockets. I am personally waiting for a quote right now and am very curious to see exactly how deep my pockets need to be. BUT it has started and I believe that now it's just a question of time (I'm guessing  less than 10 years) before you simply hit the disconnect button in ChemDraw, look through the suggestions that appear on your screen and pick the one that you like best.
And there is more. Another game changer is already here and everyone with a PC can do this: Machine Learning. My next post will be on this topic that we are already using to great effect at my work place. D!

Thursday, June 21, 2018

Transfer of nasty stuff with a syringe and needle

Synthetic organic chemists often have to transfer something pyrophoric, toxic, volatile, smelly etc. from a commercially acquired sealed bottle such as a Sigma-Aldrich Sure/Seal bottle using a needle and syringe. Even with great care it has a tendency to drip from the needle tip, which is the last thing you are interested in. Now a Danish team has published a simple DIY solution that should be adapted broadly since it solves the problem and increases lab safety.
Basically they have developed a 3D printed mount for the sealed bottle that makes is easy and safe to remove what you need (using both hands) and the needle tip is contained inside a small airlock during transport to the reaction vessel. I have taken the liberty of inserting a figure from the paper above that describes the set-up nicely. If you use this set-up and remember to always employ Luer locked syringes I believe that most accidents can be eliminated and that we can avoid another Sheri Sangji incident in the future. D! 

Wednesday, June 20, 2018

Quitting Academia

In my previous post I promised sharing my reasons for quitting academia. I just celebrated my 1 year anniversary in big pharma and boy did I make the right decision. So what was the problem for me? First of all my problem was not isolated to my geographical location. I have former academic colleagues all over the world and things are pretty much the same all over the place. In fact, relatively speaking I had it pretty good in Denmark compared to other countries. For the record the places I have heard about are limited to Europe, Asia, Australia and North America. Maybe things are fantastic in South America and Africa. I sincerely hope so but I would be surprised.
For context: I am male (born 1971) and held a position as a non-tenured Associate Professor in medicinal chemistry at the University of Copenhagen.
So in brief of the top of my head here are 10 things I was fed up with:
  1. Writing grant applications ad nauseam and having them rejected
  2. Applying for money for just about any insane idea that anyone could come up with (the curse of no tenure. You can’t be picky. Money is money.)
  3. Not getting funding for your application in the field where you are a specialist, either because a) it is not innovative (just more of the same), or b) it is too innovative and high risk and they don’t believe you can pull it off. (I have tried getting both answers for the same application depending on which funding body I sent it to)
  4. Finally getting funding for the totally insane project idea that you know close to nothing about. I was rather good at getting these
  5. Top-tuning my CV to fulfill criteria set by funding bodies and governments. I cannot begin to tell you how much I detest the H-index and other ridiculous systems that determines how good you are (can you believe that this was my main motivation for staring to write reviews? You gotta pump that H-index!)
  6. Submitting you manuscripts to journals where you believe they will get rejected only in the hope that you might get a better impact factor
  7. Submitting your good manuscript to a completely reasonable journal and having it rejected due to poor peer-review. When will someone come up with a smart solution to that problem?
  8. Receiving manuscripts for peer-review that should never have made it past the editorial office. I should note that the difference between journals is huge. Some editors take their job seriously and spend the required time on it. I have much better experience with the society owned journals from the RSC and the ACS than the rest
  9. That being a great teacher despite what they may say counts for absolutely nothing where it matters (i.e. tenure and $ £ €). Here I must be fair and say that this is not universal. Some of the best universities in the world prioritise and reward teaching (whilst others pretend they do so)
  10. That the infrastructure is terrible. Constantly instruments breaking down and me attempting to fix it so that the research projects can keep going. Obviously not a problem at the top universities or if you are a Professor with lots of money
Well that’s enough ranting for now :-) I’ll try to post something more cheerful next time.

Do I miss anything? Yes, I miss my students. My greatest pleasure was to train the guys in the lab to become independent research scientists. But pretty much everything else you can stick where the sun don’t shine. D!

Monday, April 23, 2018

Industrial Postdoc in Chemical Development of Green Solid-Phase Peptide Synthesis

It's been awfully quiet here in recent years. However, you readers are still very active on the blog and it clearly continues to be a good resource for synthetic organic chemistry students, which is great. Last year I decided to say goodbye to my University career and move on to a position in the pharmaceutical industry. I've had a lot of questions regarding why I did so. It's a rather long story so I will reserve that for another time. Anyway, to get to the point the reason for posting is that I am looking for a Postdoc for our department. If you are an experienced peptide chemist interested in joining our team and can see yourself having a career at Novo Nordisk in Denmark in the long term you should have a look at our job ad hereD!

Friday, April 28, 2017

Catalytic Hydrogenation - A Farewell to Alcohol(s)

We have a project in my group on bitopic ligands targeting the adrenergic receptors. We recently published a perspective paper on the topic that you can check out here. Anyway, today we had a project meeting regarding the synthesis of bitopic salbutamol analogues.
To this end, one of the guys wanted to synthesise an epoxide as outlined above. However, to his (and everyone else surprise) even under mild conditions he managed to loose both of his benzylic alcohols in the process. The crude product is of excellent purity and he isolated the over-reduced phenol in >90% yield.

This is a common problem but it really is trial and error. I would say that the case above is the most extreme example I have seen considering that it was run at atmospheric pressure and room temperature. It brought memories back from when I was a PhD student. The very last reaction I did in the lab was an attempt to reduce an alkene, however, as you can probably guess what I got out as the major product was the deoxygentaed molecule. However, this reaction was somewhat more messy than that above and the desired molecule may have been hiding in the mixture as well. D!

Wednesday, March 01, 2017


I guess it is old news but it only caught my eye today at the BBC website. Apparently Nature did a survey last summer (2016) were scientist were asked if they had "failed to reproduce another scientist's experiments"? What really surprised me was that only 70% on average said yes to that question. Obviously, scientists from all disciplines participated in the survey and chemistry did better in reproducibility than biology and medicine (when judged by themselves) but it looks pretty bleak overall. In synthetic organic chemistry, I would estimate that >95% of chemists have been unable to reproduce a published synthesis (as in get any of the desired molecule and not necessarily just the same high yield). Personally, I have had methods across the impact factor landscape fail in my hands, from Synlett to Nature Methods. On more than one occasion everything has just decomposed and gone black. Unless it is published in Organic Syntheses it's a bit of a lottery. Anyway, both articles are quite interesting and worth reading (although they are somewhat depressing). D! 

Monday, February 20, 2017

Dry Column Vacuum Chromatography (DCVC) - The Movie!

I have on several occasions been asked to make a DCVC video tutorial and quite liked the idea of doing so. Thus, I have started my acting career as you can see in the video below. I think the video will be a useful guide for first time DCVCers. For more info you should consult this and this blog post on DCVC. Many thanks to the University of Copenhagen's Communication Department, in particular Jacob Lejbach Sørensen, for investing some time in making this possible. D!

Friday, September 05, 2014

Total Recall - Synthetic organic chemistry is kinda slow and complicated!

To everyone's surprise I spent a day in the lab the other day doing some actual real life research. I forgot how hard, slow and complicated that stuff is. It would probably not be a bad idea for supervisors to leave the office and spend a day doing some lab work occasionally. I certainly appreciate what the guys are doing more after that ordeal. During my brief lab exposure I was reminded of the common messy lab balance problem. It is almost more common to find the balance littered with chemicals, dirty spatulas etc. than in a clean and tidy state. Anyway, the guys in my lab have sorted this out. A panda seems to do the trick. D!

Friday, December 27, 2013

Curly Arrow - Established 18th October 2006

It really is becoming the rule rather than the exception that I forget Curly Arrow's birthday. Its been running for 7 years now and as always here are some stats on the year that has passed. As you can see the lack of new posts really isn't deterring people from using all the info posted here over the years (Although visitor numbers are in decline for the first time). Hopefully I can squeeze a few post out in between everything else in 2014. D! 

From 18th October 2012 to 18th October 2013:
Absolute unique visitors: 36,032
Total visits: 42,428 ( 116 visits/day)
Page views: 68,627
Average time on site: 2:24 min
Top 10 most frequent visitors identifiable:
(1) University of California San Diego
(2) Oxford University
(3) Universite de Liege
(4) Johannes Gutenberg-Iniversitaet Mainz
(5) The Scripps Research Institute
(6) University of Cambridge
(7) University of California Irvine
(8) Stanford University
(9) ETH Zürich
(10) Columbia University
Top 10 countries that visit the blog:
(1) United States
(2) United Kingdom
(3) India
(4) Germany
(5) Canada
(6) Australia
(7) Japan
(8) Denmark
(9) France
(10) Netherlands