Reproducibility!

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! 

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!

Green

This is what 40 g of the depicted indole looks like after one recrystallisation. It really shouldn't be green but it is very pretty and even better it's analytically pure. D!
Okay, okay people. Is the photo more to your satisfaction? D!

100th Anniversary

Wow, I just realised that I've passed the 100 posts mark a while back.

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The Coffee Break section has been updated with a new comic website called The Perry Bible Fellowship. Fantastic stuff that you really should check out. Also there's been a fair bit of activity at Electra Lady Land so that's worth a visit if your into the arty stuff. D!

Hard Science

There's some seriously hard science in the latest issue of ChemComm. D!

The History of Curly Arrows

Christmas is approaching rapidly and I am off from work until 4th January. I will try my very, very best to do nothing work related for the next 2 weeks (Could be tricky. Fingers crossed)
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This years Christmas post is a tribute to Robert Robinson for inventing the curly arrow. It really is fascinating to think how recently we have have come to think about molecules the way we do now. The whole idea of bonds between atoms and sharing of electrons to make up covalent bonds really isn't as old as one would think. So hats off to Robinson who published some fantastic papers back in the 1920s where he introduced the concept. Back in the 20s Robinson was the first to draw stuff that we would recognise as curly arrows today using curly arrows to explain (and successfully predict) the outcome of reactions. Ingold was another champion in this area of chemistry who embraced the ideas put forth by Robinson (but apparently forgot to credit him for it!) and expanded it to include resonance effects and introduced stuff such as SN1, SN2, E1, E2 etc.
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Merry Christmas and Happy New Year to all the Curly Arrow readers and to Robinson and Ingold for being on top of things. See you all again in 2010. D!

The Colour of Chemistry Part II

Yesterday one of the PhD students was having a bit of fun iodinating with Iodine monochloride. D!

The Colour of Organic Chemistry

As a synthetic organic chemist what I would like at the end of the day are some white or colourless crystals. However, off-white, tan or yellow amorphous solid is more or less what you expect to end up with. But when I get bright pink, purple and green stuff I really don't know what to make of it. D!

Butt-in-diol?

Old school 1,4-butynediol. A wondeful and cheap building block. D!

Stereogenofobia and Electra's Art

I have previosuly been moaning about the fear of stereogenic centers that industry seems to suffer from here. So it was with great pleasure that I read Derek Lowe's latest contribution to Chemistry World were he appears to share some of my views.

Derek Lowe is a medicinal chemist running the hugely succesfull blog In the Pipeline. If you don't already frequent this blog you should get started. He shares interesting stuff about all aspects from synthetic organic chemistry, science and society, what's going on in industry etc.
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On a completely different note, I have added a new link to the Coffee Break section (Bottom right of the page) called Electra Lady Land. A friend of mine is an artist and I am a great fan of her work so I have decided to promovate her stuff here. Go have a look at her paintings. D!

Coffee Break

I'm having coffee and missed having some some Curly Arrow links to fun stuff. So a list of links has been added (bottom right on the front page). Chemical Stick Figures and xkcd are personal favourites. Also Org Prep Daily has started posting again and so has been upgraded from a chemistry resource to a blog.
Have a nice weekend, D!

A Cyclopropane Amino Acid Bites the Dust

"Ceterum autem censeo,

Carthaginem esse delendam"

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In recent years I have been getting somewhat annoyed with this fear of chirality that is quite widespread in industry and to some extent in academia. Stereogenic centers tend to make synthesis, purification and characterisation more complicated so I can see why it is convenient to avoid it all together and just Sonogashira yourself to death? The compounds that come out of all this tend to be very flat and aromatic and yet industry is puzzled why they aren't getting more new drugs to market. I strongly suspect that there is a very finite number of potential drugs in the flat aromatic category and that we may be getting to the end of the line.

Nature is asymmetric and three-dimensional (nucleosides, amino acids, carbohydrates...etc.) so why are we not devoting more energy to chiral molecules in drug discovery? By now there are many robust and general asymmetric processes and there is the chiral pool (more like a chiral ocean really) so getting into some exciting chiral medchem isn't really that difficult.

Anyway, the reason for this tantrum is the sad news that  Eli Lilly's very cool cyclopropane glutamate analogue LY2140023 has failed phase II trials. This class of compounds has been under way for a long time against a very difficult target and the culmination at Lilly is a densely functionalised beast with 4 contiguous stereocenters. Well CNS is a horrible area to do drug discovery. First time around the drug did really well but this time around placebo was more effective than LY2140023! Hence, Lilly is giving it another shot in clinical trials. Hopefully they will get this sucker back on track. I'd love to see something like this make it all the way. D!

What is a liquid?

I recently had dinner with some chemists and after a bit of red wine the question "What is a liquid?" popped up. The reason the question popped up is the gas sulfur hexaflouride. I had never heard of this stuff before but allegedly you can float solid objects on top of it. Intuitively, I would say that if a ship can sail in it it's a liquid but things clearly aren't that simple. There's quite a few videos with this stuff on the web. In this particular video they float an object on some SF6 in a fish tank (I'm assuming the video is not a hoax). So what is the definition of a gas/liquid? Obviously it' a density thing. Did anyone out there pay attention when they had physical chemistry and would they care to explain it to a simple preparative chemist? Also what is the least dense liquid out there? Besides pentane (0.626 g/cm3) I can't come up with much that has a density below 0.7. D!

The Periodic Table of Elements

One of my non-chemist friends recently introduced me to The Periodic Table of Videos. This is a very cool and informative website.
I've learned lots of stuff since I started watching these videos. Thumbs up to the University of Nottingham for this excellent initiative. D!

Cisplatin is my friend!

One of my best friends has just recovered 100% from cancer because Cisplatin rocks. Here's a bit of inorganic chemistry courtesy of Wikipedia:

Cisplatin was first described by M. Peyrone in 1845 and this year it celebrates its 30th FDA approval anniversary. D!

Guidelines for giving a truly terrible talk

I'm giving a presentation in a month's time which reminded me of the stuff below. Unfortunately, I can't remember what web site I got this stuff from but apparentely it's from "35-mm Slides: A Manual for Technical Presentations", by Dan Pratt og Lev Ropes. Surprisingly many scientists seem to use these guidelines. Here we go:

"Strict adherence to the following time-tested guidelines will ensure that both you and your work remain obscure and will guarantee an audience of minimum size at your next talk. Continuity of effort may result in being awarded the coveted 5:00 P.M. Friday speaking time at the next national meeting." Slides:
(1) Use lots of slides. A rule of thumb is one slide for each 10 seconds of time allotted for your talk. If you don’t have enough, borrow the rest from the previous speaker, or cycle back and forth between slides.
(2) Put as much information on each slide as possible. Graphs with a dozen or so crossing lines, tables with at least 100 entries, and maps with 20 or 30 units are especially effective; but equations, particularly if they contain at least 15 terms and 20 variables, are almost as good. A high density of detailed and marginally relevant data usually prevents penetrating questions from the audience.
(3) Use small print. Anyone who has not had the foresight to either sit in the front row or bring a set of binoculars is probably not smart enough to understand your talk anyway.
(4) Use figures and tables directly from publications. They will help you accomplish goals 2 and 3 above and minimize the amount of preparation for the talk. If you haven’t published the work, use illustrations from an old publication. Only a few people in the audience will notice anyway.
Presentation:
(1) Don’t organize your talk in advance. It is usually best not to even think about it until your name has been announced by the session chair. Above all, don’t write the talk out, it may fall into enemy hands.
(2) Never, ever, rehearse, even briefly. Talks are best when they arise spontaneously and in random order. Leave it as an exercise for the listener to assemble your thoughts properly and make some sense out of what you say.
(3) Discuss each slide in complete detail, especially those parts irrelevant to the main points of our talk. If you suspect that there is anyone in the audience who is not asleep, return to a previous slide and discuss it again.
(4) Face the projection screen, mumble, and talk as fast as possible, especially while making important points. An alternative strategy is to speak very slowly, leave every other sentence uncompleted, and punctuate each thought with "ahhh", "unhh", or something equally informative.
(5) Wave the lights pointer around the room, or at least move the beam rapidly about the slide image in small circles. If this is done properly, it will make 50 % of the people in the front three rows (and those with binoculars) sick.
(6) Use up all of your allotted time and at least half, if not all, of the next speaker’s. This avoids foolish and annoying questions and forces the chairman to ride herd on the following speakers. Remember, the rest of the speakers don’t have anything important to say anyway. If they had, they would have been assigned times earlier than yours. D!

Farewell Australia

Goodbye and thanks for all the sunshine, chicken parmis, red wine and last but not least all the fish. Blogging will resume again sometime in July. D!

The Robots are Coming

Posting on Curly Arrow is already a very erratic affair and things will not be improving for a while. There is less than two months til the big move back to Denmark. I'm experiencing total organisational chaos and trying desperately to obtain some results in the lab before it is too late. So please be patient.

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I'm sure that the following paper from Journal of Medicinal Chemistry is great (I haven't read it). The title is certainly great.

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Designing Active Template Molecules by Combining Computational De Novo Design and Human Chemist's Expertise

Eric-Wubbo Lameijer, Reynier A. Tromp, Ronald F. Spanjersberg, Johannes Brussee, and Adriaan P. IJzerman

J. Med. Chem., 2007, 50, 1925-1932

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D!

100% Edible

Finally, I'm returning to normal. I'm back at the University working at full force and I've got the energy to do a bit of blogging again. Let's start with a nice and easy post. One of the new people at the University turned up with the following Fluka product the other day. Pretty sweet and good quality chocolates too. Apparently, Fluka is a Swiss based company and once a year (around Christmas I believe) they give their customers a truck load of these containers.One of the guys in the lab immediately grabbed the phone and gave Fluka Australia a call to hear if they stocked this item too. Unfortunately, this appears to be a Switzerland only bonus. The product also isn't listed in their catalogues.

Also my "great" idea of introducing Google adds on Curly Arrow was short lived. A lot of the adds where completely irrelevant to this blog so it's all been deleted again. D!

Open Access Journals - Beilstein Journal of Organic Chemistry

It's amazing how unpredictable life is. Only four months after I started my job in biotech I'm heading back to academia. Not that there was anything wrong with the job but I've been given an opportunity to return to Denmark (which always has been the long term plan) so I'm going with the flow. I recently had a post on open access journals and was moaning a fair bit about how we don't have any decent chemistry open access journals yet. Well I was wrong. A colleague alerted my attention to Beilstein Journal of Organic Chemistry (BJOC). This is the best attempt I've seen yet. They are publishing a reasonable number of papers, the quality of the material is good, the journal gets indexed by all the important organisations and it is absolutely free. The impact factor is still low (ISI WoK: 0.35) but this should improve with time. So check it out.

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The past year I've been involved in setting two labs up and whilst searching for information on equipment etc. I've been quite pleased with the Google adds people have on their web sites. I found a fair bit of the stuff I needed this way so I've decided to give it a go here at Curly Arrow. So sometime in the very near future adds will start appearing on Curly Arrow that should be useful to people interested in purchasing lab equipment. D!