Sunday, 30 June 2013

#chemclub Roundup 12

Once again, here's a roundup of the best of the #chemclub Twitter feed from the last two weeks. (Confused? Read this.) The second review will go online early in this week; this unfortunately coincides with the death of Google Reader tomorrow. If somehow you both use this reader and live under a rock, you may need a replacement; personally I'm using Feedly, which now has a pretty green button on this page.

Tuesday, 18 June 2013

Acc. Chem. Fail.

Last week there was an online campaign to create pressure to publish negative results. The potential benefits are obvious, and are nicely summed up in the cartoon by Nik Papageorgiou: if we had a database (like Reaxys) of "stuff that doesn't work", we could all save time, effort, and money going down futile routes. Much of it has been coming from biological quarters, but it's something that chemists have proposed too.

(Quick disclaimer: I've not really been part of this conversation, so if my comments have been rebutted elsewhere please do correct me.)

I'm a little skeptical of whether it's really as simple as "publish your negative results!", at least when it comes to chemistry*. It's not enough to say "we tried these conditions and it didn't work". This isn't going to be too helpful; there are a million reasons why a particular reaction might not work in your hands (look at BlogSyn for a detailed example of this). For such a resource to be useful it has to be thorough: you have to try to pin down why your reaction doesn't work, and that's not a trivial matter.

The journal behind last week's campaign even say as much:
"For negative and null results, it is especially important to ensure that the outcome is a genuine finding generated by a well executed experiment, and not simply the result of poorly conducted work.  We have been talking to our Editorial Board about how to try to avoid the publication of the latter type of result and will be addressing this topic and asking for your input in a further post in the next few days."
I don't know how it is in the biomedical sciences, but in chemistry I'm not sure it's going to be clear up front why a reaction doesn't work. Ensuring that it is a genuinely negative result will take time, and is likely to be of limited interest to the wider community; understanding why the reaction doesn't work is yet more work, but will be much more useful.

Who is going to take the time and effort to really thoroughly study a failed reaction and figure out why it works except a methodology group that is already studying that chemistry in depth?

To illustrate my point I'll use an example from my own area, self-replicating molecules. In 2008, Vidonne and Philp reported an attempt to make a self-replicating rotaxane. I'm going to stop here to express my sincere admiration at the scale of a project like this. I'm not aware of any other attempts to achieve something like this; it blows my mind a little bit.

From Tetrahedron 2008, 64, 8464–8475.
The paper is a thorough study of the system and runs to 12 pages. They report careful planning and a detailed kinetic model; the synthesis and analysis of the system; and experiments to figure out exactly what is occurring in this complex system and why it didn't behave as expected. Judging by the abstract, this represents a huge portion of Vidonne's thesis.

This is the kind of detailed work needed to make negative results worthwhile - both to publishers and to other researchers. Anyone can break a reaction, but it takes time and attention to detail to turn that into useful knowledge.

That said, there are lesser steps that can be taken to get useful negative results into the literature without expending so much effort. For example, methodology papers could include tables of substrates or conditions that didn't work in their SI; synthesis papers could (and often do) discuss methods that failed for them.

An interesting alternative is the robustness screen recently proposed by Collins and Glorius. They describe a standardised 'kit' that may allow chemists to quickly get an idea of whether a particular set of reaction conditions is likely to tolerate functional groups and so on. One strength of this idea is that it would require chemists to report negative results: "our conditions tolerate A, B, and C, but are shut down by X, Y, and Z".

To sum up: it's easy to say "publish your negative results!", but in chemistry at least it's not clear that it's that straightforward. To be worth publishing, or worth anything, you have to have an idea why the results are negative, or negative results need to routinely reported alongside positive results.

What do you think negative results could contribute to chemistry? What information would you need for a negative result to be useful to you?

* to clarify: none of my comments are meant to generalise to all of science, or beyond organic chemistry, really. In other fields this may well be more straightforward.
** thanks a big huggy bunch to @PeONor and @craigdc1983 for having a look over this post before it went up.

Sunday, 16 June 2013

#chemclub Roundup 11

Here's the usual roundup of papers from the #chemclub Twitter feed and various chemistry blogs in the last fortnight. If you're not sure what #chemclub is, click here.

Tuesday, 4 June 2013

#chemclub Roundup 10

Here are some highlights from the #chemclub Twitter feed in the last two weeks. The eagle-eyed amongst you might have noticed that #chemclub was featured in the Blogroll column of this month's Nature Chemistry. Thanks to Dr. Jay for the kind writeup!

Starting this month I've expanded the scope of #chemclub to include monthly articles about different topics in chemistry by various authors. The first is about protocells and can be found here. If you'd like to get involved in this project, get in touch!

On the blogs, Derek Lowe has discussed a few papers, including a Nature paper that uses microwave spectroscopy to determine absolute configuration (check out the comments for a great explanation of the physics of this in chemist-speak) and a paper which images the probability distributions of hydrogen - take that, anti-realism.

If you're into med chem, the OSDD Malaria team have put out a call for input on their open-source drug discovery project. They want advice on which of their candidate molecules they ought to focus on for the next round of synthesis and evaluation. Even if this isn't your area, it's an interesting project and worth checking out.

Jan Jensen offered some insight into the process of peer review, including full comments from reviewers on two papers. Both have now been accepted (to PLOS ONE and J. Chem. Ed.).

Finally, at Open Flask, Dane asks: what's your favourite journal?

Onto some papers: Nessa posted an Org. Lett. describing the synthesis of nitriles by the cleavage of internal alkynes. It's a cool and somewhat unexpected transformation - Derek Lowe describes it as one of those "reactions you probably wouldn't have thought of".
James shared a paper from Nat. Chem. about the templated synthesis of carbon nanotubes. This new method allows control of the chirality of the product, and produces tubes of diameter very close to that of the template.
Fellow protocell fan Vittorio posted another Nat. Chem. paper from Adamala & Szostak. Here, a dipeptide catalyst contained within a vesicle catalyses the formation of a different dipeptide. The product is hydrophobic and binds to the membrane, altering its properties and leading to growth at the expense of other vesicles which lack the product. In effect, the small molecule can be thought of as a 'metabolite' which allows more efficient growth and division, and assimilation of molecules from a competitor. It's an interesting demonstration of simple competition between model protocells.
SeeArrOh shared a Carreira paper from Science. By combining two chiral catalysis (one Ir-based and the other cinchona-derived), the four diastereomeric products of an allylation reaction could each be selectively synthesised from the same starting materials. The the ees are pretty much all >99%, and drs are frequently >20:1, and generally good. Definitely worth reading if you're into catalysis!
Karl posted a review from Acc. Chem. Res. by Muratsugu & Tada about their approach to catalysis. Put briefly, they try to emulate the active sites of enzymes by attaching Ru catalysts to oxide surfaces with a substrate-like molecule bound to the metal, and then surrounding the bound complex with layers of silica. When the ligand is removed from the metal, what's left is a shape roughly like that of the intended substrate, creating the basis for selectivity.
Dr. Paco is reading a tutorial review from 2008 by Otto on systems chemistry. I've read this before and it's good, a great introduction to the area if you're not familiar with it. Naturally I'm a big fan of the section on self-replicating molecules...

Finally, Tony Arash shares a paper which uses an N-heterocyclic carbene to catalytically activate sugars as formaldehyde equivalents in a Stetter reaction. The carbene 'chews up' carbohydrates from the terminal carbonyl to generate carbon nucleophiles for a 1,4-addition. I can't quite put my finger on why, but there's something really appealing about this for me.

Saturday, 1 June 2013

#chemclub Reviews: Protocells

Welcome to the first in a new series: #chemclub reviews. Every month there'll be a short article about an area of chemistry, the idea being to allow readers who are only vaguely familiar with a topic to learn some more as quickly and painlessly as possible. I hope that these will be a useful supplement to your regular reading!

The key goal is to provide you with context, or the 'big picture' of a topic, to help you more fully appreciate new research in the area. The articles will assume basic chemistry knowledge, or at least the ability to use Wikipedia.

Naturally, I won't be writing all of these: my own knowledge is pretty limited. A few friends have kindly offered to write about their own areas of interest or expertise. If you'd like to get involved, drop me an email!

First up is a topic close to my own area of research: self-reproducing protocells.