Microsoft and InChIKeys

Earlier this month, I hinted at how InChIKeys might be used in Googling for chemical information, well, I missed a trick. In 2006, at the BioIT World Life Sciences Conference and Expo, Microsoft announced the formation of the BioIT Alliance. The Alliance is a group of organizations working together to realize the potential of personalized medicine. Now, the Institute of Pure and Applied Chemistry (IUPAC) has joined the club. IUPAC’s contribution to the enterprise will lie primarily in being responsible for establishing standards in chemical information transmission. In this regard the InChI/InChIKey system will be critical to success.

IUPAC representative Stephen Heller says: The InChI/InChIKey is the first publicly available unique chemical identifier, which allows scientists to link and exchange information and data across the chemosphere and in the life sciences. The InChI/InChIKey is the molecular equivalent of a Digital Object Identifier (DOI), the journal article tracking code. “The InChI/InChIKey is an agent of change and an agent of the future for linking the chemical, biochemical, and biomedical information and data on the web,” says Heller. It will now provide the Microsoft BioIT Alliance with a much simpler, and free, way to work with chemical information.

Poison Darts and Poison Pens

Epibatidine

Many years ago, I reported on the earliest synthesis of the analgesic compound epibatidine from the poison frog Epipedobates tricolor. You’ll notice I was careful to say poison frog, not poison dart frog. In the prestigious pages of Science in 1993 I wasn’t quite so careful and describes this creature as a poison dart frog.

It was a simple mistake to make as there were dozens of references in the literature to this species as the toxic secretions of this and other frogs as being used in poison darts. However for E tricolor, this wasn’t and isn’t the case. It’s a toxic frog most certainly, but no one has ever tipped their darts with its secretions. The venom in the deluge of letters from readers wishing to highlight and correct my error while I was still a cub reporter writing freelance for the journal via its Cambridge office was enough to make my toes curl.

Anyway, the analgesic properties of epibatidine became famous. Several hundred times more potent than morphine, but with none of the addictive properties of its fellow opiates, it seemed that its career as a new painkiller was set. It has, as you can see from the picture, a quite stupendous chemical structure, which took several attempts to yield a total synthesis. Efforts are still ongoing I see from a quick scan of the current literature. A paper in JOC this month, has Armstrong, Bhonoah, and Shanahan wrestling with an aza-prins-pinacol approach to the 7-azabicyclo[2.2.1]heptanes of which epibatidine and its close cousin epiboxidine are examples.

It still surprises me that so little work seems to have been done to bring this compound and its analogs into the pharmaceutical fold. For instance, only a limited number of analogs have actually been synthesized and evaluated in vitro and negligible numbers have been tested in vivo. Given the enormous market a non-addictive painkiller with opiate-like power might share, I wonder why. Any pharma readers care to enlighten us?

Taking the P

Toilet

Sciencebase readers of a certain age will know exactly what I’m talking about if I were to ask, “Can I have a P, please, Bob?” The Bob in question being host of a TV game show for teens too long ago into my past for me to admit when. The Bob in question was almost marginally embarrassed by the question and mildly amused, although it referred only to the choice of letter.

Taking the P of course is a standard British pastime, although I’m not 100% certain about a couple of research papers published today in a special issue of the International Journal of Environmental Technology and Management on composting of solid waste and whether the P remains firmly in place or not.

One of the co-authors on the first paper (Post-composting techniques of digested household waste) is based at the WTO, and no, before you ask that’s not the World Trade Organization it is the World Toilet Organization in Singapore. Honestly. Apparently, the organization has a Toilet Entertainment link on its website (http://www.worldtoilet.org) and says that November 19th is World Toilet Day. Hmmm. Makes you wonder…that’s also the week of Thanksgiving in the US…

The second paper is entitled “Experience in improving fertilizer value of compost by enriching with urine” . The researchers say that “ecological sanitation concepts are closing the loop of nutrients contained in wastewater with agriculture.” Nice…

Personally, I’ve been taking the P to our compost heap for years. My wife, unfortunately, thinks it nothing more than an excuse to indulge in a little back garden naturism. It’s the phosphate and nitrogen content, I tell, her, they are good for the cucumbers! It is to no avail, of course, and the neighbours have told me they prefer theirs with dressing.

By the way, the Bob in question – Bob Holness – of BBC TV’s Blockbusters fame was the first radio broadcast actor to play James Bond.

Critical Acclaim

David Bradley Science Writer

A criticism levelled at the Sciencebase blog recently was that the subject matter is too diverse (check out the category list in the menu, to see what they mean) and that I, as blogger-in-chief on this humble site, simply alight on a subject of interest, almost at random (a random list under the heading Posts from the Past can be found in the menu), and fire off a short item about said subject (take you pick). Another reviewer tells me, rather positively I think, that the site is like a one-man New Scientist, and yet another suggests that although some of the posts are a bit long, there are plenty of subjects I don’t cover that I really ought to, and sometimes, perish the thought, I get things inadvertently not quite right…or even wrong!

Well, as they say, you cannot please all of the people all of the time. However, I’ve been blogging, in one sense or another, on subjects that interest me for almost two decades for dozens of different publications who more often than not come back for more and tell me that their readers are very happy with the words I produce. If the subjects I choose to write about on Sciencebase, my personal blog, are not to everyone’s taste 100% of the time, then, I’m afraid that’s just the nature of blogging.

I read dozens and dozens of blogs, sometimes it seems like thousands, usually via RSS, on a daily basis. I have to admit that not all of those I subscribe to are fascinating, in-depth, and unique 100% of the time. But, they do provide me with insights and inspiration into a wide range of subjects much of the time. Occasionally, they make me as angry as a least one recent commentator feels about Sciencebase.

But, like I say, a blog is personal. I write it for me first off and hope that it entertains or informs others across the blogosphere. Some of the posts are flippant, shallow, puerile even, some are more profound, and some of them reflect additional thoughts and comments from the various scientists I interview for the other publications I write for and link to.

I presume that a few of the more than 2500 regular RSS subscribers served each day, the average 8000-plus daily visitors who kindly turn up at my virtual door, and the many uncounted readers who see syndicated versions of this site on Techdispenser.com and elsewhere, actually quite like my seemingly random choice of subjects, appreciate my efforts at a unique and honest writing style, and find my alleged attempts at a one-man science portal to be, to some degree, informative, useful, and fun. If that sounds pretentious, then be thankful I didn’t use the words stakeholder, leverage, or incentivize.

Mighty Neat Diabetes Target

mitoneet protein

In this week’s SpectroscopyNOW column, I cover a wide range of subjects with the usual hint of spectroscopy, informatics, and crystallography. First up is a study on a unique protein, MitoNEET.

The protein was previously identified as a putative site for the activity of diabetes drugs known as thiazolidinediones, or which Actos is an example. The determination of the protein’s three-dimensional crystal structure coupled with bioinformatics information demonstrates that it is a clear target for small molecules. The mode of action was previously linked to an entirely different protein, according to biophysical chemist Patricia Jennings and physicist Mark Paddock, and their colleagues at the University of California at San Diego (UCSD) and Stanford Synchrotron Radiation Laboratory and the Hebrew University of Jerusalem, Israel.

“This is the first time that a protein like this has ever been found,” explains Paddock, “It is a brand new structure, a unique beast, which makes it an exciting target for structure-based drug design.” The structure shows two protomers intertwined to form a unique dimeric structure, explain the researchers, this constitutes a new fold not only among the 650 known Fe-S proteins structures but also among all known proteins.

Given that there is at least one clinically tested drug in this area it shouldn’t be too long before other novel compounds that can moderate insulin by interacting with MitoNEET are being investigated. However, it does highlight once again just how hit and miss the drug discovery process can be if the thiazolidinediones are not actually targeting the protein with which they were initially thought to interact.

Also in this week’s issue, more on the crab metabolite story from last week, copper blues and the toxic mouse, and Rod of Titania, the new superhero that could improve energy technologies and sunscreen simultaneously.

Dental plans

Teeth by David ShankboneMaybe I shouldn’t tell you this online, and my son will be more than a little miffed, if he reads this, but he recently had a trip to the orthodontist and is now the proud owner of an upper teeth realignment device, a brace, as we used to know them in the good, old days. So why am I telling you this?

Well, the fitting of the brace raises an interesting question of mechanics as to what the brace is actually doing. It is composed if small metal plates effectively fixed along a piece of tough wire. The plates are seated on the front of the teeth, with one plate on each tooth and the wire is anchored somewhere in the back of the mouth. Now, what I cannot understand is why. The upper incisors of the orthodontic patient in question seem to slope inwards, rather than jutting out. My gut feeling is that pushing the teeth backwards with little metal plates is going to make them more recessive if anything. So, how does this system work? What are the true forces involved in dental realignment and how does pushing the teeth in the direction they are already going make them move into the correct position.

Maybe all will become clear with the next visit…meanwhile, I have to thank the NHS for funding this work, without it, it would be costing us a small fortune…

UPDATE: Treatment went well and he now has lovely straight teeth, as does our daughter who followed the same path a few years later.

Culmination of Fulmination

Mercury fulminate

German chemists recently determined the crystal structure of a compound the alchemists knew as “Knallquecksilber”, but which goes by the formal name of mercury(II) fulminate. The compound is highly explosive, sensitive to heat and shock and its control in the form of a detonator material for dynamite gave Alfred Nobel his big break.

The new crystal structure corrects some previous mentions in the scientific literature, by revealing it to be an almost linear molecule. But, never mind the chemistry you can read more about that in the September issue of my Intute Spotlight. It is that name that intrigues me. Knallquecksilber.

Quite literally it means “bang quicksilver”, quicksilver being silvery mercury’s liquid alchemical name. Bang quicksilver hardly slips off the tongue, so a better translation might be exposive quicksilver, which isn’t quite so crisp and subtle as the German word, but close.

I had a chat with a German chemist friend about the etymology of this name and the lack of a subtle literal translation from the German into English. It’s common to quite a few German words, zeitgeist, meaning literally time-ghost or spirit of the times, being another favourite. My friend pointed out that knallen (verb) describes something exploding with a big bang, a
Knall, the crack of a whip or the banging of a door might be described using knallen in German, for instance.

But, he also pointed out that the English name for this salt itself – mercury fulminate – harbours an explosive origin. Fulmination, of course, being another word for a violent explosion and so perfectly apt for describing big bang quicksilver.

Periodic Table Names

The Periodic Table,   #58 on Explore 11/14/07
Periodic table names, it’s an odd phrase, what does it mean? It obviously means something to dozens and dozens of visitors to ChemSpy.com who hit the site from the search engines looking for that exact phrase. I puzzled for ages trying to figure out what these visitors were after. Were they simply looking for different types of periodic table? There are lots of sites out there that discuss traditional, modified, circular, three-dimensional and some rather bizarre periodic tables (there are PTs for desserts and sexual positions, (NSFW) you may care to know).

Then I spotted a follow up search from a cluster of subsequent visitors, they were searching for not just “periodic table names” but “periodic table with names”. Then a query came in that was even more explicit – “periodic table with element names”. Duh! I thought to myself. They’re simply looking for a PT that not only has the elemental symbols but gives the full name of the element to which the symbol refers. Well, the answer to that query is easy – yes. Best among a big bunch has to be good friend Mark Winter’s site based out of Sheffield University WebElements.

So, there’s the answer. Unless you know otherwise…

More Periodic tables:

PT rings and more, PT of visualisation methods

There is Iron in Them There Bills

Have you ever wondered what it would be like to make a dollar bill smoothie? Well popular science guru Steve Spangler certainly did and with the help of a super powerful neodymium magnet he demonstrates in the video below just how much iron you would get if you were stupid enough to drink the smoothie. The iron is present in certain magnetic inks used to print a fistful of dollars.

There’s iron in them there bills…you might say!

Dollar bill video

So, now you’ve watched the video, you’re probably wondering, what are neodymium, or rare earth magnets and why is it so much stronger than a standard fridge magnet? Well, unlike conventional ferric or iron magnets, neodymium magnets are composed of iron, boron, and as the name would suggest, neodymium. The general chemical formula for this alloy is Nd2Fe14B which basically means for every 14 iron atoms in the material there are two neodymium atoms and one boron atom. That special blend (pardon the pun), however, means they can be up to about twenty times stronger than conventional ceramic magnets. Check out the HowStuffWorks site for a simplistic explanation of magnetism.

I asked magnetic expert (soon to be) Dr James Stephenson, who has probably forgotten more about magnets than I ever knew, why it is that the neodymium, or neo, magnets are so much stronger. The strength of a permanent magnet is down to how strong are the individual magnetic moments of the atoms from which it is composed and that’s down to how many electrons can be aligned in each atom, he explains.

Put simply, “Rare-earth magnets, also known as nib magnets, are stronger because the individual atomic magnetic moments are stronger and that adds up to a stronger magnetic field overall,” he says. Taken individually, an isolated atom of a rare earth element, such as neodymium, has gaps in its so-called d [electron] f-shell. When Nd is alloyed with boron and iron those gaps get filled up to a maximum of 14 electrons in the f-shell of each Nd atom, this results in a very strong dipole. “In other words,” Stephenson adds, “more electrons means more current and as a result the magnetic field due to each dipole is higher.” So, there you have it.

By the way, it’s not illegal to blend a dollar bill unless you plan on trying to spend it later, but to be on the safe side bring a friend along, not only can you make sure it’s their dollar bill you blend, but you can claim it was their idea when the FBI turn up at the door too!

Male-Female Crabs Split their Difference

Male-Female Crab

David Johnson and Robert Watson thought they had seen all there was to see in the Chesapeake Bay in almost three decades until they pulled out a crab from the way that had a male left half and a female right half. Now, that crab, acquired by Romuald Lipcius of the Virginia Institute of Marine Science at the College of William & Mary, has moved sideways into the world of natural metabolites where its gynandromorphic peculiarities have helped scientists, for the first time, discover that some molecules can be made only by one sex and not the other.

The male-female crab is a unique example of the blue crabs. It turns out that the males of this species produce a natural metabolite that is absent in females. This suggests that some complex biochemistry is underway that is activated only in males. Robert Kleps of the University of Illinois at Chicago and colleagues have isolated this small molecule and identified it as 2-aminoethylphosphonic acid (AEP), an uncommon but well-documented natural metabolite.

We used low-field NMR using phosphorus-31, to observe the small molecule, explains Kleps. He points out that science tends to get lost in the rush for higher field NMR running hydrogen-1 and carbon-13 on 100 kilodalton proteins. However, he adds that, “Even low-field NMR spectroscopists can make interesting discoveries. I’m very happy to have stumbled over this metabolite, while doing basic research on invertebrate metabolism.”

So, why might the existence of a metabolite in the males of this blue crab species and not the females have any bearing on our everyday lives? Well, there are well known differences between the sexes in people, such as disease susceptibility, anatomy and drug metabolism. Kleps points out that these differences might in fact be due to the presence or absence of a crucial metabolite.

Now that the existence of a sex-specific metabolite has been found for one animal the search is on for others, including ones that might exist in people.

For more details on the NMR study check out my column on SpectroscopyNOW.com, the research paper itself is available in Plos One.

You can hear a description of the crab from Lipcius here and listen to Kleps’ podcast