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!

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! 

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!