Chemistry – Page 28 – David Bradley

Healthy PubMed Searching

This post is more in the bio camp than the chemo field, but may be of interest both to chemists with a life sciences investment and/or hypochondriacs in your lab.

The Healia health portal has added a specially designed PubMed/Medline search to their site that helps consumers retrieve abstracts of scientific articles published in biomedical journals in a more user-friendly way than the standard PubMed search. The system still searches the National Library of Medicine’s (NLM) PubMed/Medline dataset, which includes more than 17 million abstracts and citations from approximately 5000 biomedical journals published since the 1950s. One of the unique capabilities of the additional Healia Clinical Trials Search is that you can restrict searches geographically and map locations of study sites.

It is possible to filter a search to Professionals, Females, Males, Kids, Teens, Seniors, African Heritage, Asian Heritage, Hispanic Heritage, Native Peoples and a few other categories.

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.

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.

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

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

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

ChemModLab Enters ChemSpider Web

A new project that combines work from two distinct cheminformatics groups will form a new system for the delivery of modeling and identification of commercially available compounds for biological testing.

The North Carolina State University Exploratory Center for Cheminformatics Research group, developed ChemModLab to compute quantitative structure-activity relationship (QSAR) models and this will be pulled together with the almost 18million structures currently in the ChemSpider database. These structures are sourced from the scientific literature, chemistry database providers and commercial chemical vendors and screening library providers.

“This data collection provides an ideal basis for combing the QSAR capabilities of ChemModLab with the compound collection and indexing of ChemSpider to allow identification of virtual hit compounds via in silico screening, says ChemSpider boss Antony Williams.

Googling InchiKeys

What it is to be an InChI – at once unique and representative of so much and yet meandering and potentially far too long. Now, IUPAC has launched a new version – InChIKey – a condensed version of the InChI chemical identifier that will be a fixed 25-characters long.

This new format will make searching for molecules on the web much simpler by preventing unpredictable breaks that happen with the conventional seemingly endless InChI strings for some of the more complex compounds. It will thus facilitate a web-based InChI lookup service and allow InChI to be stored in fixed length database fields and so make chemical structure database indexing far easier. One of the most important aspects of this new approach to the InChI is that it will allow verification of InChI strings across networks. Imagine the woe, for instance, if the tail of your Viagra InChI were cropped short in transmission…

IUPAC admits that there is a finite, but very small probability of finding two structures with the same InChIKey. The odds are of the order of billions to one against, but chemists are making more and more new substances as we speak so you never know when there might be a data collision. It is very, very unlikely, however.

The new release can be downloaded from the IUPAC web site (www.iupac.org/inchi). What effect this will have on my passwords for chemists idea, I simply don’t know!

Post-Labor Day SpectroscopyNOW

Earth's core

My latest science news round-up for SpectroscopyNOW.com is now live:

The problem of the core – Understanding how the bulk iron at the earth’s core is packed together and with what other lighter elements is critical to revealing the origins and evolution of the earth and precisely how it generates its magnetic field.

Fluorinated agents at the ready Intrusive biopsies for people with cancer could be sidestepped thanks to the development of fluorine-containing contrast agents by David Parker and colleagues at Durham University.

Baby light – Near-infrared light could allow researchers to see activity within the infant brain even while the tot wriggles and giggles.

High-field NMR morphs caffeine structure – High-field NMR has overcome the problem of spectral ambiguity in nitrogen-rich compounds, thanks to efforts by Canadian scientists. The team has studied two anhydrous polymorphs of the stimulant, caffeine, and has found that, despite extensive disorder, both caffeine polymorphs reveal the characteristic structural signatures of crystalline compounds.

Diamonds out of Hades – Raman spectroscopy could turn the history of the early Earth upside down and hint that conditions were suitable for life as little as 250 million years after its formation, pushing back the so-called Hadean era several hundred million years.

Sweet nanoreactor – A one-pot chemical reaction system based on nanoscopic capsules embedded in a polymer membrane has been devised by researchers in The Netherlands. The nanoreactor system allows cascade reactions to be carried out that would otherwise require multiple distinct reaction steps with time-consuming and wasteful separation and purification stages.

ChemAxon Hits a Nerve

ChemAxon recently announced version 2 of its Instant JChem, a desktop application for working with chemical and
other data on local and remote databases. Version 2 adds forms and form building, relational data support, advanced query
building and multiuser access.

Instant JChem is a software application for all major operating systems which bundles ChemAxon’s Marvin and JChem enterprise cheminformatics toolkits with a local database engine to give an ‘out of the box’ solution for research informatics. Personal use is free, although if you want to go “enterprise” you will have to check out their price list.