Sugars in Particular

One of the big problems with chemical structure algorithms is that they can’t, in general, cope with the ways that chemists are accustomed to drawing sugar molecules. They will lose the stereochemistry around the sugar ring, collapsing D-glucose, say, on to L-glucose, not to mention allose, altrose, gulose and all the others.

(ChemDraw, I should note, can interpret chair stereo properly, but it is very much an exception.)

The first step in determining correct stereochemistry for a chair atom is recognizing a chair hexagon. That is the subject of this post.

Have you ever been in the same car as a satnav (US readers: this is the same as a GPS)? Whereas a human navigator will give general instructions like “go straight over all of the roundabouts till we reach the Red Lion”, a satnav only ever gives single-step, local instructions. “At the roundabout, take the third exit.” “In 100 metres, turn left.” Machine structure perception is rather like this. Instead of apprehending in an instant that the hexagon is a chair or a boat like you or I would, the algorithm needs to step around the structure atom by atom, bond by bond.

The trick to identifying what kind of hexagon we are dealing with is to see whether, at each atom, we turn left or right. If we keep turning in the same direction all the way round, then we have a regularish hexagon. If we turn once in one direction, then twice in the other, then once in the first, then twice in the other, then we have a chair. There are six other sorts of hexagon you can draw, and they’re all depicted below alongside the corresponding sequences of turns.

Some of them are familiar, like the boat, the twist boat, and the envelope. Others, less so.

What happens when we’ve identified the atoms in the chair? I’ll come to that in more detail soon, but in the mean time here’s the slides from the ACS Spring meeting in New Orleans:

We have now also made further steps to integrate ChemSpider with Southampton University’s ELN, LabTrove, following on from an eScience tool that Stephen Wan from CSIRO had developed with the University of New South Wales to text mine LabTrove ELN blog posts to identify chemical names and link these to the relevant ChemSpider compounds. LabTrove is an open source blog-based system which can be used for recording and sharing experimental findings. Previously, if an image of the compound was to be added to an experiment blog post, it would be necessary either to upload it as an image (following drawing it in a separate drawing package) or to paste in a link to the image in another website (following a separate internet search in another browser window). We have now added the ability to click a button directly when adding or editing an experiment to launch a search of ChemSpider and when the required compound is found, an image of it can be added to chemspider simply by clicking on it, as can be seen in this demonstration video:

The editing controls in LabTrove are based on TinyMCE, a WYSIWYG editor which is used in a range of blogs, including WordPress. This means that this same ChemSpider plugin can also be used to insert compound images from ChemSpider from any other blog or website that uses a TinyMCE editor too.

If you have a LabTrove installation which you would like to add the ChemSpider plugin to then simply update your installation with the latest source code from LabTrove’s SourceForge website.

If you have a website or blog which uses a TinyMCE editor which you would like to add the ChemSpider plugin to then simply download this zip file, extract the folder in it and move the “chemspider” directory created to your tinymce plugins folder. Then, in your tinymce initialization process, add the plugin “chemspider” and the button “chemspider”.

The original concept of SyntheticPages was brought to life by a group of academics who developed the original platform and format (and of course the members of the research community who embraced it and submitted articles). When ChemSpider became part of the RSC the concept of a community resource for reactions seemed like a complementary partner to the database of chemical compounds that we had established. With this in mind we were fortunate to collaborate with the hosts of the original SyntheticPages platform and, combining our resources and visions, we provided a new platform for submission. A short presentation about CSSP is online here.

CSSP today is quite well known within a small community of chemists but comments from the audiences that we expose the work to are very positive on the value of the platform and the way that we have developed it to date. Certainly the authors can get 10s of thousands of hits on their articles based on the published statistics! The “Leaderboards” are all available online for anyone to review.

We believe that everyone can see the value of building a directory of reliable, robust reactions that can continue to evolve through feedback and questions. But more that that, we see the potential benefits for:

• Young scientists as a portfolio of their work that can enhance a resumé
• Building systems that can contribute to Alternative Metrics  – Already people are developing platforms, such as Impact Story. CSSP presents the perfect opportunity to build such online contributions will become increasingly visible and important for a scientist in parallel, of course, with the present metrics for contribution and reputation.

We are presently working on a new system for “rewards and recognition” for contributors to our online databases and we will be rolling this out in more detail in the near future. It will be our way of recognizing the contributions of our users for their commitment to communicating science to the community using our platform as one of their vehicles to do so. As part of this activity we are also choosing to recognize present and future authors for their contribution of 5 or more SyntheticPages to CSSP. We will be contacting previous authors to ensure that they receive a brand spanking new, off the press, CSSP Lab coat to thank them for making their syntheses available!

Discussing the project to recognise and celebrate the top contributors to CSSP, Dr James Milne Managing Director RSC Publishing said the following:

“The ChemSpider SyntheticPages lab coats are a great idea, as they highlight a number of fantastic contributors, and also the role of CSSP within the broader publishing context. RSC Publishing strives to serve the needs of researchers worldwide, through publishing and disseminating high quality content, and this database of practical synthetic procedures certainly adds to this knowledge base.  I’d personally like to thank these contributors for supporting CSSP through their publications.”

If you haven’t already qualified for a CSSP lab coat by submitting 5 or more procedures; What’s stopping you? We look forwards to reading your submissions…….

Image taken from Wikipedia (http://en.wikipedia.org/wiki/File:Plughole.JPG#file)

Water is one of those chemicals that we tend to take for granted until it reminds us; usually because we have too much or too little of it. In one way or another, water seems to have insistently nagging me this year. In the Spring in the UK there were talks of water restrictions and droughts, while now the many places are flooded, and only a few weeks ago in the US, Hurricane Sandy proved that water could be as formidable a force as the winds.

Don’t forget water is a chemical!

Water has a huge impact on the chemical sciences – after all it is one of the most common chemicals in the world. And as such, Water features in many of the activities of the RSC, to list just a few recent examples….

• Water is one of the Priority Areas in the RSC Roadmap (http://www.rsc.org/ScienceAndTechnology/roadmap/priorityareas/waterair/index.asp)
• Last year Richard Allan, Chief Scientist at Scottish Water gave the seminar Water Sustainability – a Global Challenge (see online at: http://www.thereaction.net/events/y2011/Water_Sustainability.aspx)
• Water was featured in our activities as part of the International Year of Chemistry (2012) including the Our Children on Water – European exhibition of international art and The Global Experiment
• Moving on to the subject of water in scientific research; this year the RSC and Hermes 2012 ran a competition to find the best and most creative explanation of the phenomenon of The Mpemba Effect (the popular name for the process by which hot water sometimes freezes faster than cold water) – a process that until recently I was entirely unaware of.
• And of course, ChemSpider has a record about water which brings together lots of data – and links to other resources, including podcasts and videos: ChemSpider – Water .

Well, what about this webinar?

When I was still a bench chemist I have to admit that I only thought of water as something used in extractions, or to be excluded from reactions (and occasionally in tackling the mountain of dirty glassware that I’d accumulated). But looking at the title of the latest Chemistry World Webinar – it looks like there are still many aspects of water that I have to learn about. The webinar is free, if the details below pique your interest; you only need to follow the link and sign up to watch the live Webinar. If you can’t watch at that time or are reading this post after the Webinar has taken place – don’t worry you can access the archive of all of the Chemistry World Webinars at: http://chemistryworld.gav.co.uk/webcasts/past-events.php.

The importance of water quality in the laboratory

4 December 2012, 13:00 – 14:00 (GMT)
Free webinar

Speaker: Dr Estelle Riché – Senior Scientist, Merck Millipore

How are water contaminants affecting your lab results?

Join us for our next live and interactive Chemistry World webinar to learn why and how water is purified to yield the various water qualities used in the laboratory.

By the end of this free one-hour knowledge-share, you will be able to:
• identify the different contaminants potentially present in laboratory water
• understand the potential impact of these contaminants on laboratory applications such as HPLC, LC-MS, etc.
• understand how various water purification technologies remove these contaminants from laboratory water
• make better choices for the water you use in your laboratory work
Click here to find out more and register for free
This webinar is brought to you by Chemistry World in partnership with Merck Millipore.

Dodgy stereochemistry is a persistent problem.  Even if someone knows all of the stereocentres in a particular molecule, they might not necessarily draw them in a way that a machine, or even a person, can interpret.  There are rules about whether the pointy end or the blunt end of a bond indicates the stereocentre, and it’s surprising how often you see them done wrongly.

Today I’m going to talk about a particular IUPAC recommendation for drawing stereocentres that might at first glance seem surprising, the rule that you may only have one stereobond at a given stereocentre. If you have a wedged bond attached to an atom, you can’t have a hashed bond attached to the same atom. And vice versa.

Why is this?

You might think that as you’re supplying more information, you’re making the diagram easier to interpret. However, you’re running directly counter to the normal principles of communication.  You’re being more informative than required, and this sets off alarm bells in the reader.  What are you trying to say?  If you ask a passerby the time and they say “Well, it’s half past six Greenwich Mean Time” you’re entitled to wonder why they’re quoting the timezone. Maybe they’re trying to be funny.

Paul Grice thought about this whole problem in the 1970s and came up with a set of four principles, summarized in maxims, that listeners (or readers) assume that speakers are following.  These are they:

• Be Truthful. Do not say what you believe to be false. Do not say that for which you lack adequate evidence.

Let us hope that this one is implicit in any chemical drawing!

• Make your contribution as informative as is required.  Do not make your contribution more informative than required.

If you have two methyl groups coming off an atom, do not make one wedgy and one hashy. You are adding no new information!

Do not mark carbons with the letter C unless your target audience is schoolchildren.

• Be relevant:

On the grand scale: do not illustrate an article with any old molecule—make sure the molecule mentioned is actually relevant.

On the scale of the drawing itself, however: If you have three bonds about an ordinary p-block atom, for example, make sure they’re at 120 degrees to each other.  If they aren’t, for example if two of them are at right angles, the reader will infer that something odd is going on.

• Be clear:

Make sure all your double bonds actually look like double bonds rather than a single bond parallel to another single bond.  I suspect a lot of the success of ChemDraw is down to the fact that it produces attractive, clear chemical drawings.

Do people ever flout the maxims on purpose?

Oh yes.  People often flout the maxims when trying to be funny, or in a political interview.  Similarly there are all kinds of Gricean violations in the chemical drawings you see in patents: bonds which do not quite extend all the way to atoms, R groups labelled as Y (particularly dangerous as Y is yttrium!) or Q or W (also tungsten) or some other unusual letter and so forth.  Exactly why this happens so much more often in patents than in journal articles is left as an exercise for the reader.

Natural Product Updates (NPU) gives you the molecules involved in key developments in natural product chemistry. Thanks to our work in interpreting what chemists mean, not just what chemists draw, ChemSpider now links to NPU’s data for 13800 natural products since 2005, of which 7800 are brand new to ChemSpider.

Where ChemSpider has information on a compound in NPU you will see the image above, as in, for example, calothrixin B. This is a link to NPU page on the RSC Publishing Platform.

Soon we’ll be integrating more of our graphical databases into ChemSpider. Watch this space!

If you are at ACS Fall 2012 don’t forget the other ChemSpider at ACS Fall 2012 in Philadelphia events.

Fig. 1. Galactose in perspective.

Take the drawing of galatose in Fig. 1. Even if you’re not a chemist, you can tell which bits of the ring are at the front and at the back, which bonds point up and which bonds point down. If you actually are a chemist, you’ve been trained to apply this geometrical intuition to work out what’s going on at each of the five stereocentres.

However, if you ask the InChI algorithm about the stereochemistry of this molecule, it’ll say that there is no stereochemistry in there and you’re looking at a stereoless description of which atom is attached to which. Since we use the InChI algorithm to say whether two records describe the same molecule, this puts us in a quandary, and there are thousands of entries in ChemSpider that come from just such a drawing and hence lack stereochemistry.

I’ve been developing algorithms to take these allegedly flat drawings and render them in such a way that InChI and other algorithms can identify the stereochemistry and turn the side-on view above into the eagle’s-eye view in Fig. 2.

Fig. 2. Galactose from above.

Currently we can standardize chair sugars and Haworth-projection sugars, and this is being built into CVSP. More on our methods and what we will be doing with them, not least tidying up the erroneous ChemSpider entries, soon!

The SpectraSchool resource was originally developed with the University of Leicester who collected and assigned many of the spectra that displayed within the site. Now that SpectraSchool is part of Learn Chemistry we have helped to integrate new features, including a new HTML 5 based spectrum viewer that provides interactive display of spectra. The fact that this is based on HTML 5 means that the spectrum can be viewed on just about any device that has a modern browser (eg, computers, tablets, phones or even touch screen tvs).

A student visiting the site has the ability to zoom in on peaks and to see which features of a chemical structure give rise to a particular peak in a spectrum; by selecting either a peak or a particular part of the structure (see the highlighting of the methyl group in the structure of caffeine below and the corresponding peak in the adjacent 1H NMR spectrum).

SpectraSchool and Chemistry in the Olympics are great examples of the RSC’s new microsites which bring together lots of great resources and tools in a fresh and exciting interface.

Take a look at SpectraSchool and LearnChemistry today we welome feedback through the in page feedback links or connect with us and other chemistry educators in the Talk Chemistry forums. Why not start exploring this great (free) educational resource today?

* The Introduction to Spectroscopy was developed in collaboration with the University of Cardiff

Several members of the ChemSpider team will be attending the conference; both to give presentations and also to chat/answer questions on the booth. If you are attending the conference please drop by and say Hello and ask any questions that you have (you might even be able to get a free coffee – available on a first-come first served basis from 11 am on both Monday and Tuesday). We will also be running an exciting ChemSpider competition to coincide with the conference. You can get details from our Booth #701, or by checking out the ChemSpider blog.

There will be two key ChemSpider events in Philadelphia:
A special On-Stand demo – Monday 20 August, 11 am, Booth 701
“ChemSpider and You: A workshop exploring how ChemSpider can help you find chemical information” – A 2 h workshop for both newcomers to ChemSpider and experienced searchers alike. 10am-12pm Tuesday 21 August, Exhibit Halls A-B, Workshop Room 2 (You can register for the workshop via the conference website – we will try and accommodate anyone who just turns up on the day.)

In addition members of the ChemSpider team are giving a number of talks, including some early glimpses of exciting new tools that we are working on. The presentations are listed below – for more details including the abstracts for each of the talks see the Technical program.

‘Mining public domain data as a basis for drug repurposing’, Philadelphia Marriott Downtown, Room 302/303, Sunday 19th August, 4.15PM – 4.40PM

‘Putting chemistry into the hands of students – chemistry made mobile using resources from the Royal Society of Chemistry’, Pennsylvania Convention Center, Room 109B, Sunday 19th August, 10.50AM – 11.10AM

‘Feeding and consuming data to support Open Notebook Science via the ChemSpider platform’, Philadelphia Marriott Downtown, Conference Room 307, Monday 20th August, 2.05PM – 2.30PM

‘Approaches for extraction and “digital chromatography” of chemical data – a perspective from the RSC’, Hilton Garden Inn Philadelphia, Salon D, Monday 20th August, 2.30PM – 2.55PM

‘Delivering an online service for validating and standardizing chemical structure files using the ChemSpider platform’, Philadelphia Marriott Downtown, Franklin Hall 6, Tuesday 21st August, 9.15AM – 9.35AM

‘ChemSpider compound database as one of the pillars of a semantic web for chemistry’, Philadelphia Marriott Downtown, Grand Ballroom Salon H, Tuesday 21st August, 4.55PM – 5.10PM

‘How can the International Chemical Identifier (InChI) be extended to non-trivial chemicals?’, Philadelphia Marriott Downtown, Franklin Hall 6, Thursday 23rd August, 9:35AM – 9.55AM

‘Serving up and consuming community content for chemists using wikis’, Philadelphia Marriott Downtown, Franklin Hall 6, Thursday 23rd August, 9.55AM – 10.15AM

We look forwards to seeing you at the conference!