Chemistry – Page 27 – David Bradley

Organic Chemistry for Dr Hook

Molecular Networks Inc this week launched SYLVIA, software to rapidly evaluate the synthetic accessibility of any given organic structure and to prioritize thousands of structures according to their synthetic complexity. The company describes SYLVIA as the link between computer-aided de novo molecular design, chemoinformatics and synthetic chemistry.

SYLVIA scores compounds based on structural elements, similarity to commercially available chemicals and a reaction-based component extracted from reaction databases.

No doubt to the irritation of many potentially interested parties you have to purchase a license for SYLVIA, although a free evaluation download is available. Input file format is MDL, SDFile (incl. Molfile), SMILES, and CTX file. No mention of InChI unfortunately. Output is as MDL, SDFile (incl. Molfile), and CTX file. In fact, I couldn’t even find InChI mentioned on the Molecular Networks site, which is odd given this unique identifier’s potential in the field of organic chemistry.

Shopping for Genes

Leaning strongly towards the bio today, I thought I’d mention a new database for biologists that works like a shopping mall. An international team has opened a virtual bazaar, called PAZAR, which allows biologists to share information about gene regulation through individually managed boutiques. Customers may draw data for free from any boutique or extract information from the “superstores” that aggregate data of similar types.

In deciphering the human genome sequence, researchers hope to understand the “when and where” of gene expression because it could underpin novel cancer therapies, stem cells treatments for degenerative disease, and explain complex diseases such as diabetes.

No More Chocolate Headaches

chocolate-chunks Does eating chocolate give you a headache? What about red wine? Cheese, perhaps? Yes, well read on to find out how a space-age detector developed to look for signs of life on Mars could soon become the kitchen gadget of choice for anyone who suffers a painful reaction to their food.

According to a paper to be published in the November 1 issue of Analytical Chemistry, researchers at the University of California Berkeley have developed a fast and inexpensive test suitable for domestic use that can spot the toxins in certain foods, particularly “aged” or fermented products, including chocolate, cheese and wine. The device could be engineered into a PDA or other handheld device for greater portability and instant access to information on any toxins found in a particular food or drink.

The test detects biogenic amines, natural toxins known to trigger headaches, cause facial flushing, lead to nausea, and raise high-blood pressure. Current tests for biogenic amines usually take hours in a specialist laboratory with bulky and expensive test equipment. With the aim of packing the test into a package small and efficient enough for a Mars landing, Richard Mathies and colleagues, have simplified the whole system down to a lab-on-a-chip device (portable microchip capillary electrophoresis) that produces results in just five minutes.

“These toxins can be a serious health problem and are more common than people think,” says study Mathies, “They are hidden in a wide variety of foods, so having a quick and convenient way to identify them will help consumers avoid them or at least limit their intake.”

The toxins, which include tyramine, histamine, and phenylethylamine, are particularly hazardous to people with reduced levels of the enzyme monoamine oxidase and to people on older antidepressant drugs which act as MAO inhibitors. For these individuals the risk of a seriously dangerous rise in blood pressure is very possible.

Biogenic amine tyramine “Some foods have more biogenic amines than others,” explains Mathies, “but you cannot tell in advance because they aren’t listed on the food labels.” Even a single glass of wine has been known to trigger elevated blood pressure, heart rate and headaches in some people, he adds. He suggests that food manufactures and wine producers should be obliged to list biogenic amine content in their products by law. Although if they did, then this would preclude the need for the test kit, I assume, so the research team could concentrate on sending it to Mars instead.

A Natural Blowtorch

Oxy-acetylene blowtorch

Nature’s blowtorch is an enzyme system that oxidizes toxins, drug molecules, and other noxious molecules found in the body ready for excretion. But, understanding exactly how this molecular machinery has been an ongoing research job for many years. Now, Ayyalusamy Ramamoorthy, Lucy Waskell, and Ulrich DÃ¼rr, at the University of Michigan, Ann Arbor, have turned to the powerful analytical technique of solid state NMR spectroscopy, to reveal important structural details about the enzyme without removing from its native site in the cell membrane.

The standard approach to working out a protein’s structure would be to extract it from the membrane, crystallize it, and then blast it with X-rays to get a clear picture of the position of every atom. Unfortunately, that does not show you the structure of the enzyme system while it is on the job. Instead, NMR bathes the sample in a strong magnetic field and then scans it with radio waves to see how the atoms respond. Depending on how the atoms in the enzyme are connected and to which and how many other atoms it is possible to build up a structural picture of the complete system.

Rams and his colleague have now found that nature’s blowtorch operates like an oxy-acetylene blowtorch. It is composed of two enzymes working together. The first enzyme, cytochrome P450, is the “acetylene”, which does the actual job of toxic breakdown, while the “oxy”, to stretch the metaphor, perhaps a little two far, is a second enzyme, cytochrome b₅.

You can read more details in this week’s SpectroscopyNOW column from David Bradley together with news of the latest developments in using CDs and CD players as analytical tools for medical diagnostics and remote environmental testing. Team leader Ãngel Maquieira of the Polytechnic University of Valencia, in Spain, told me that the The robustness of a CD is perfect for collecting environmental samples, it can be used offsite, immersed in a mixture of water, sample and reagent for several minutes, washed, and then stored in a pretty much standard CD box for taking back to the lab. Once back on site, the CDs can be played in a standard computer CD drive modified with the addition of a planar photodiode to detect the signal from any sample on the CD.

Also in this week’s issue researchers in California have developed a simple algorithm, which they have integrated into a download Excel spreadsheet that gives wine makers better control over the phenolic content of their product. The input data for the spreadsheet come from a computer-interfaced ultraviolet spectrometer, which can detect the different kinds of phenolics and tannins in the wine at different stages of the production process. You can read more on that here.

Japanese women This issue, I also report on how detecting the differences between young and old hair using Raman spectroscopy is now possible, even if the hair is highly pigmented. You can find out more about that here.

Finally, another enzyme story, this time about PKA, protein kinase A, and the power of X-ray crystallography, which I disputed somewhat in the NMR item!

Smelly alchemist

In the Alchemist chemistry news section over on ChemWeb this week – two smelly discoveries caught my nose. The first points the way to a clearer understanding of how we smell, while the second explains the biochemistry of geosmin, the earthy smell of freshly turned soil and the particular bouquet after rain showers.

We now learn from GATech scientists how a sensor array can weigh up atmospheric or aqueous pollutants and why stirring a dendrimer solution could explain the origins of life. Finally, this week, researchers in California have taken the first steps towards building a gamma-ray laser using a quasi-molecule based on positronium. And, the award mentioned this week goes to the RSC’s Project Prospect team, which received the 2007 ALPSP/Charlesworth Award for Publishing Innovation.

Also, in pharma news this week an interesting development reported in FierceBiotech regarding the issue of whether or not clinical trials are safe. I’ve included it in the comments on the write-up I did on the TGN1412 clinical trial that went disastrously wrong in 2006.

Chemical Blogspace Stats

The Chemical Blogspace Zeitgeist page is an interesting round up of chemical blogs. The ChemSpy blog resides at #9 in the top fifty chemistry blogs (trailed slightly by Sciencebase at #13). That in itself is quite gratifying, but it is the other statistics that make for more entertaining reading. Apparently, ChemSpy has a reading index (Gunning-Fog as it happens, based on the most recent three months posts) equivalent to a scientific journal (index of 14). Reading Sciencebase on the other hand is like picking up a Thomas Pynchon novel. But, at least, the site doesn’t rank alongside
In the Pipeline, The Bioenergy Blog, Cheminfostream, and it’s a puzzle…, which all have a Gunning index of between 17 and 20 and so are apparently equivalent to reading a “Manual for Taiwanese DVD player”. Not my words, Cb’s!

By the way, sites also seemed to be ranked on the basis of their use of InChIs, it’s worth checking out this page to see what molecules are being discussed and to see their structures.

Scrolling down, I learn that Sciencebase is fifth most active blog, while, not unexpectedly, Chemspy is not in the top 20 based on activity (frequency of posting). Once again, Sciencebase features in the top 20 based on wordiness (average posts being around 500 words), while Chemspy’s terse commentary (until today, that is) nestles much further down the tree. The final statistic of interest is the measure of friendliness, which might also be referred to as blog nepotism, or blogotism, to coin a word, just how many times a blog links out to other sites in the chemical blogspace. Again, not unexpectedly, neither Sciencebase nor Chemspy feature in the top 20, basically because my posts tend to be standalone write-ups referencing the primary literature and only occasionally have a need to backlink to other blogs. That said, I’d be interested to know if ChemSpy readers would prefer to see more outbound links to related content elsewhere in the chemical blogspace. Please leave your suggestions in the usual place.

Plain or Vanilla Pheromones

NOW with working links!

The latest issue of chemistry webzine Reactive Reports is now online, in this month’s issue:
Plain or Vanilla Some men smell of vanilla while others smell of urine, but it is not always down to personal hygiene or ice-cream tainted Cologne.

Light Controlled Magic Bullet Targeting diseased tissue directly with the drug to teach it, the so-called magic bullet, came a step closer thanks to work by Senior Lecturer in Pharmaceutics Colin McCoy of Queen’s University Belfast and his colleagues.

Insecticidal Synthesis Professor Steven Ley of Cambridge University and his colleagues over the last two decades have been on a chemical odyssey to make the natural insecticide azadirachtin.

Fire Resistant Paint A way to toughen up the latex particles used to make emulsion paints has been developed by UK chemists.

What is the Structure of Taxol

I’m a bit confused, I had assumed that the complete stereochemistry of the anticancer drug Taxol (paclitaxel) had been assigned years ago, presumably at the point when its first total synthesis was performed if not before. I’ve written about the compound several times, in particular reporting that first total synthesis of the compound in the UK paper, The Daily Telegraph.

However, it seems there is ambiguity spreading across the net. Most notably, ChemSpider’s Tony Williams tells me (and has blogged about it), there is a potential discrepancy in the structure of Taxol given in Wikipedia.

Now, I know for a fact that Wikipedian chemist Martin Walker (see my recent interview with him in Reactive Reports) who is a member of the ChemSpider advisory board will already be on the case to double check and check again the structure in Wikipedia.

Aside from the politics of open access information and data, it is crucial that services like ChemSpider and Wikipedia give their users the correct structure for any given compound. There must be dozens of synthetic organic chemists who have carried out full stereochemical assignments on Taxol and know for certain the correct structure. Perhaps it’s time we had a referendum so that the winning structure could be posted to Wikipedia and other information repositories.

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.