Sugary Antifreeze Molecule Found In Alaskan Beetle

image: Carl Gustav Calwer - wikimediacommons

I've been visiting family out of town - we got here just in time to be snowed-in for Christmas. So I thought some wintry chemistry would be appropriate.

Slashdot recently had a listing about a new anti-freeze molecule that has recently been found in the Alaskan beetle, Upis ceramboides. Anti-freeze molecules have been observed in a variety of plants and animals that help them resist damage from the formation of ice crystals in their tissues. All previous anti-freeze molecules have been proteins, but this new one is a sugar. It may also have a lipid component, but that isn't clear.

The sugar, xylomannan, is a polymer of mannose and xylose. Originally the researchers assumed that the anti-freeze compound in their beetles was a protein, like other known anti-freeze compounds. However they couldn't visualize it with electrophoresis, and the UV-vis and NMR spectra didn't show any sign of peptide bonds or aromatic sidechains like tyrosine or phenylalanine. Instead, the NMR was consistent with a sugar molecule, which was confirmed by GC/MS.


Research Article: A nonprotein thermal hysteresis-producing xylomannan antifreeze in the freeze-tolerant Alaskan beetle Upis ceramboides

Slashdot Science Story | New Antifreeze Molecule Isolated In Alaskan Beetle

Blondie Christmas Carol

A little Christmas music before going back to some cool chemistry.


Via Blondie - We Three Kings Music Video (2009) Boing Boing

Atomic Cookies

I've been away for a while.  Here's a little treat for the holidays:

Courtesy of Not So Humble Pie, a cooking blog that has been posting recipes for science themed treats recently.

Via Not So Humble Pie: Science Cookies: Atom

Blue Sun

The Astronomy Picture of the Day site has this cool image of the sun.  The visible spectrum of hydrogen has 4 lines called the Balmer Series. I can see at least three of them myself, but the fourth is on the edge of my eyesight.  To me the lines have the colors Red (656 nm), Blue (486 nm), Violet (434 nm) and Violet (410). This picture was take using a filter that only lets through the Hydrogen Alpha line, and then color inverted to appear blue.  I'm not sure why they changed the color, but it looks cool.  Take a look at the larger version of this picture at the link.

Image Credit & Copyright: Alan Friedman (Averted Imagination)
Link APOD: 2009 November 4 - Blue Sun Bristling

Guitar Duet with only One Guitar

This looks a little awkward, but the amazing thing is that some times his left hand is fretting the strings that she is playing, and she is fretting the strings that he is playing.  When I play, both hands are working in synch - I would think it would be hard to NOT have both hands playing the same strings.

via Neatorama

Symmetry is Not A Spectator Sport

We just finished discussing Stereochemistry in my Organic class.  Since stereochemistry ultimately boils down to a matter of symmetry, this seems like an opportune time to show this video.

32 Years Without Small Pox

It has been 32 years since a case of Small Pox was last diagnosed.  According to Wikipedia:

The last naturally occurring case of indigenous smallpox (Variola minor) was diagnosed in Ali Maow Maalin, a hospital cook in Merca, Somalia, on 26 October 1977. The last naturally occurring case of the more deadly Variola major had been detected in October 1975 in a two-year-old Bangladeshi girl, Rahima Banu.

We have heard a lot about vaccines in the last few years.  The fact is: vaccines work. The Variola major version of Small Pox has (had?) a mortality rate of 30-35% - out of every three people who got the virus, one died.  In the 20th century, it is estimated that 300-500 million deaths were caused by small pox.  Because of the small pox vaccine, no one gets this disease. Anywhere in the world.

(Image: wikimedia commons)

Via An Anniversary Worth Celebrating – Neatorama

A Timely Video for Lab Day: Safety Song

Made by some UC Berkeley Grad students. See more of their work at The Sounds of Science.

via Safety Song: musical number about lab safety - Boing Boing

Drug Microscopy from the Wellcome Image Awards

Image: Annie Cavanagh and Dave McCarthy

Cool image of polymer-coated drug particles taken with an electron microscope. It looks like some sort of modern art piece.  Originally in black and white, the color was added later: the drug is orange and the polymer blue.  From this year's Wellcome Image Awards.

According to judging panel member Catherine Draycotte:

"One of the reasons this image stood out as extraordinary is because it doesn't look like a natural image. It doesn't look as though it could possibly come from a microscope - it looks as though it must be computer-generated.

"This is because the particles - and those within them - are so smooth: they are artificial and have virtually no texture. The image really shows what technology can do in targeting drugs to specific purposes. This system is designed to delay the release of the drug that is contained in the smaller particles until it reaches the large intestine, where it will treat inflammatory bowel disease."

Wellcome Image Awards 2009 | Winners' gallery | Scientific and medical images

Commercial green fuel from algae still years away

Scientists and investors are lured by the pond scum's natural oils that can be extracted and refined into fuel.

Algae grows fast and absorbs greenhouse gases along the way. Plus, the lowly lifeform uses less land, water and other resources than the corn or soybeans used in first generation biofuels, alleviating concerns that those renewable fuels would cause food shortages.

It's disappointing that this may take a decade to be practical, but it seems like a no-brainer to use algae rather than terrestrial plants as a source for renewable bio-fuels.

via Slashdot: Commercial green fuel from algae still years away | Reuters

Desktop Electron Microscope

From SlashDot:

Wired previewed the desktop-sized Hitachi TM-1000 Electron Microscope a while back. Light microscopes can magnify up to 400X (1,000X at lower quality) — just enough to see bacteria as shapes — but this one offers 20X to 10,000X, giving some amazing pictures. Unlike traditional electron microscopes, this one plugs into a domestic power socket and specimens don't need any special preparation; it's point-and-shoot, much like your typical digital camera.

Cool!  But what I would really like is a desktop NMR!

Slashdot Science Story | An Electron Microscope For Your Home?

Aberranone - an Unusual Gorgonian Molecule

The Caribbean Sea Whip, or Gorgonian,  has been the source of a myriad of unusual natural products. The latest example being Aberrarone, which has a unique carbon skeleton, not observed before.

 Aberrarone gets its name from the Latin word aberrare, meaning "not typical or usual."  The authors suggest that the aberrarane skeleton  may be formed via a rearrangement from other gorgonian compounds such as Elisapterosin A or Colombiasin A.  All three compounds show anti-malarial activity.

It's hard to really see the structure of these compounds in 2D. Elisapterosin A and Colombiasin A are listed at ChemSpider and if you click the 3D tab above the strucure  there you can see them in 3D. 


Rodríguez, I., Rodríguez, A., & Zhao, H. (2009). Aberrarone: A Gorgonian-Derived Diterpene from

The Journal of Organic Chemistry, 74 (19), 7581-7584 DOI: 10.1021/jo901578r

Fires spread FAST!

A couple of minutes into this video they start a fire in a simulated dorm room to show how quickly a fire can spread. This is really impressive, and a little scary.

A good reason to make sure your fire alarm is working, and pay attention when it goes off.

When I was a post doc, the house next door to us burned down late at night in the middle of winter - it was frightening how quickly it happened. We were lucky it didn't spread to our house, in the middle of Pittsburgh the houses are very close together.

Thanks to Debbie Decker on the DCHAS-L list.

Tabla Periodica de los Elementos

Ever wondered what the Periodic Table would look like in a language other than English? The Chemistry site at About.com has one in Spanish. Look for the link to the PDF version underneath if you want a nice copy to print. It even includes the newly named element 112 Copernicio (Cp)

Tabla Periodica de los Elementos

Structure of Petroleum Gunk

C&EN's cover story last week discussed advances in understanding the structure of asphaltenes. The headline on the cover describes these compounds as "Petroleum's Gunk" because of the problems they cause the oil companies by clogging their pipelines. Asphaltenes greatly increase the viscosity of crude oil - more oil would be pumped from the wells but for these things. Take a look at the structure of one example from the C&EN article:

Walkingstick Molecules

Johnny over at Ecographica has a post on defense molecules secreted by Walkingstick insects.  Head on over to Johnny's post for pictures of the Walkingsticks.

There are several species of Walkingstick, and the one described in this paper produces three different defense molecules that are stereoisomers of one another: anisomorphal, dolichodial, and peruphasmal.  Being an organic chemist, I wanted to know that these molecules look like so I did a little digging around.

The first place I tried was PubChem - only dolichodial was listed, although PubMed does have papers listed for all three compounds. Next I tried ChemSpider, and again only dolichodial was listed.  Time for a more specialized database.  Rich Apodaca is compiling a list of 64 free chemistry databases on his Zusammen Blog, and one of the databases he has profiled is a collection of pheromones and similar molecules called Pherobase.

Pherobase has a search box at the top of the page, and typing the name of each compound produced a list of google-search results.  The titles and descriptions of the search results were not completely obvious, but the pages with a file name containing "compounds-detail-" seemed a good place to look.  This gave me both a 2D drawing and a 3D structure for each of the compounds.  Go ahead an check out the Pherobase pages for anisomorphal, dolichodial, and peruphasmal.  The Pherobase page for each compound includes a 3D structure with the Jmol applet - if you want to turn of the auto-rotation, right-click in the molecule window and set Spin to "off."

Here are all three molecules side by side:

They are stereoisomers - the difference between them is the 3D orientation of the three side groups attached to the ring: dark wedges are "up" and dashed wedges are "down."  At a glance, I can't say why they might specifically be "defense" molecules.  However, much of molecular signalling just boils down to shape rather than chemical reactions - these compounds may just smell or taste bad to predators.

According to the article, the specific compounds produced by the bugs depends on their developmental stage, and even location.  The researchers raised 14 Walkingsticks and observed the types of defense molecules they produced as they grew.  The bugs they used produced a mixture of anisomorphal and dolichodial as hatchlings and the amount of  dolichodial increased after 2 months.  However, when they reached maturity they stopped producing either anisomorphal or dolichodial, and produced peruphasmal exclusively.  As adults, other populations of walkingsticks produce anisomorphal, or a mixture of anisomorphal and peruphasmal.  None of the adults produce dolichodial.

I'm a chemist, I don't know what all this means.  Something seems to happen at 2 months that changes the amount of  dolichodial they produce.  And something else happens when they reach maturity that they stop producing dolichodial.  It's interesting that adults produce one or both molecules that have the aldehydes on opposite sides of the ring - and the compound produced only by the immature insects is the compound with both aldehydes on the same side of the ring.

Dossey, A., Walse, S., & Edison, A. (2008). Developmental and Geographical Variation in the Chemical Defense of the Walkingstick Insect Anisomorpha buprestoides Journal of Chemical Ecology, 34 (5), 584-590 DOI: 10.1007/s10886-008-9457-8

From TED: John Lloyd and Things We Can't See

Reactions Using Iodine Azide without Explosions

How do you carry out organic synthesis when the reagent has a tendency to blow up?  Brandt and Wirth constructed a microreactor to do the job.  In this case, one of the main benefits of a microreactor is that very small amounts of material are needed.  Once the reactants were mixed, they passed through a capillary with a volume of 0.196 mL where they were heated to promote the reaction.

The reaction of interest was between iodine azide and various derivatives of benzaldehyde.  Under these conditions, the weak iodine - nitrogen bond breaks and the reaction involves a free radical mechanism. The aldehyde Hydrogen gets abstracted and the resulting radical reacts with iodine azide to give an acyl azide and more Iodine atoms to continue the radical chain reaction.

The resulting Acyl Azide then undergoes a Curtius Rearrangement when heated.  N₂ leaves, the benzene ring migrates from the carbonyl carbon to the first nitrogen, and a lone pair on the first nitrogen forms a pi-bond with the carbonyl carbon (replacing the bond from the benzene ring.) This produces an Isocyanate, which is quite reactive towards nucleophiles.  With excess azide ions present, the isocyanate reacts with a second azide ion (via an ionic mechanism this time) to produce the final product - a carbamoyl azide.

They don't report any explosions, but otherwise seem to have had disappointing results.  The reaction did work, but it was rather slow and gave low yields.  The yield did improve if they first distilled the benzaldehyde before the reaction, but it was still low.

Brandt, J., & Wirth, T. (2009). Controlling hazardous chemicals in microreactors: Synthesis with iodine azide Beilstein Journal of Organic Chemistry, 5 DOI: 10.3762/bjoc.5.30

Amazing Molecule Movie

Cool movie showing some of the things computational chemists do by Jan Jensen and posted on his blog, Molecular Modeling Basics.

Avogadro 0.9.8 Is Available

The latest update to Avogadro (0.9.8) is now ready.  The Avogadro Home Page doesn't mention it yet, but if you click on the "Get Avogadro" button, you will get version 0.9.8, or you could go to Sourceforge you can get the packages directly.

According to Tim Vandermeersch's blog there are no new features, but some bugs have been fixed.

via OB, Avogadro and Molecular Modelling: Avogadro 0.9.8

Visit Mr. Penumbra's 24 Hour Book Store - Wonderful Podcast

Escape Pod is a science fiction podcast magazine.  This week's episode is "Mr. Penumbra's 24 Hour Book Store" - a wonderful short story about a mysterious old book shop.  It was originally posted on Robin Sloan’s blog, and has been turned into an audio podcast by the people at Escape Pod. 

Just to give you a taste, here is the beginning:

IT’S 2:02 A.M. ON A COLD SUMMER NIGHT.

I’m sitting in a book store next to a strip club.

Not that kind of book store. The inventory here is incredibly old and impossibly rare. And it has a secret—a secret that I might have just discovered.

I am alone in the store. And then, tap-tap, suddenly I’m not.
And now I’m pretty sure I’m about to snap my laptop shut, run screaming out the front door, and never return.

The audio runs about 45 minutes and is well worth the time.  You you can read the original.

EP215: Mr. Penumbra’s Twenty-Four-Hour Book Store
Via Boing Boing

Head Music from Neurosonics Audiomedical Labs

Neurosonics Audiomedical Labs Inc. from Chris Cairns on Vimeo.

Cool video - reminds me of the Heads from the Nexus comic book.
via BoingBoing

Staying Safe Even When You Aren't in Lab

With the start of the school year, I spent a lot of time in Lab last week discussing safety.   Perhaps the first rule of being safe in the lab is to pay attention to what is going on around you, and that is true no matter what your situation.

Like the author of this article, I have studied karate.  I've been fortunate - the last time I was in a fight was eighth grade (long before I started taking karate), and I didn't start that fight.  I don't know if my martial arts training has had anything to do with it. It did help me feel a little more comfortable with myself, and self-confidence will make you less of a potential target of people with bad intentions.

How to Recognize Imminent Danger: 7 Essential Safety Rules - Stepcase Lifehack

CAS Hits 50 Million Compounds

Over the weekend, the Chemical Abstracts Service (CAS) registered its 50 millionth compound! Only 9 months ago they hit 40 million compounds. This stuff is so new that it isn't listed in PubChem of ChemSpider yet. For comparison, it took 33 years for CAS to record the first 10 million compounds.

According to the press release at CAS:

"The 50 millionth substance (CAS Registry Number 1181081-51-5) was uncovered by CAS scientists from the Examples section of a nearly 200-page patent issued by the World Intellectual Property Organization on August 13, 2009. According to the patent, "Few therapeutics are approved by the US Food and Drug Administration and other regulatory agencies for the treatment of neuropathic pain." To address this concern, a series of novel arylmethylidene heterocycles were synthesized, which included the most recent substance registered by CAS."

Check out the full press release at: 50 Millionth Unique Chemical Substance Recorded in CAS REGISTRY

Come On and Meet the Elements

They Might Be Giants, from their new album of kids' music: "Here Comes Science."

via They Might Be Giants: "Meet the Elements" music video (BB Video) - Boing Boing

A Video History of Movie Special Effects

A cool compilation of movie special effects over the last hundred years.

via IO9.com 100 Years of Visual Effects From Kong To Tron, And On - visual effects - io9

ChemSketch on Linux? Maybe not ...

Ever since I started using Ubuntu last Spring I have been looking for a Chemical Structure Drawing program that runs on Linux. On Windows, I have been using ACDLabs ChemSketch ever since version 1.0 in the 1990's. They are up to version 12, and every new release has lots of good stuff. It's available as a free download for educational use, I recommend it to my students for writing their lab reports.

When I realized that they had put out a Linux-compatible version I was really excited. ChemSketch is about the only program I use that I need Windows to run. Unfortunately it doesn't look like that's going to work out.

After you register to download the Linux installation program, you get an exe file. Unless you read carefully you may have missed the reference to CodeWeavers Crossover. EXE files don't run on Linux systems, but you can run them with a Windows Emulator which is what Crossover does. Crossover is not a free program, but it is based on a program called Wine, which is free.

I have tried both Wine and Crossover (as a free trial version) and ChemSketch seems to work pretty well with both. There is a problem though: After installing ChemSketch I can run the program just once. When you start ChemSketch you see a splash screen displayed, then a CheckBox describing ACDLabs products appears. Once you click the OK button, the CheckBox goes away and the ChemSketch window opens. In addition to the ChemSketch window, the ACDHost runs as an icon in the top panel.

The second time (and every other time) I try to run ChemSketch on Ubuntu, that icon is the only sign that ChemSketch has started. I see the splash page and CheckBox as usual, then nothing happens. I get the same result whether I use Crossover or Wine to install and run ChemSketch. The only thing I can do is right click the ACDHost icon and choose "Close All" to exit the program.

It's puzzling and quite frustrating. Obviously the program will run (once) and everything seems to work the way it does under Windows. The System Monitor shows processes for ACDHost and ChemSketch with their status listed as Sleeping. What do I have to do to wake them up? There may be a simple answer to this, but I'm still really new to Linux and I haven't figured it out yet.

Test Your News IQ - Pew Research Center

The Pew Research Center has a Science Knowledge Quiz. Go ahead and take it now, there are only 12 questions. I'll wait.

As a professional, life long science geek I expected to do well. I helps that I teach chemistry, and I'm interested in medical research, astronomy and space science.

If you look at the breakdown by question, it's not too surprising which questions most people answered correctly. And it's understandable that about half the people who took the quiz didn't know how big an electron is - that's not something most people have any personal experience with.

The question that disappointed me most was the one on antibiotics and viruses. Every time you get a cold and ask for antibiotics your doctor should tell you the answer to this one. Antibiotics don't affect viruses. When you are feeling crummy, it may seem unfair but the antibiotics won't make you feel any better except by the placebo effect. Fewer than half answered correctly. Everyone should know this, for two reasons:

1. it's wasteful and a waste of time to take drugs that don't work
2. it contributes to bacterial resistance to antibiotics, which is bad for everyone
   

Test Your News IQ - Pew Research Center
via Greg Laden's Blog

Internet Profile: Bridgehead Carbons

My "seemingly authoritative personal profile" courtesy of Personas, which is part of an exhibit at the MIT Museum. When you enter your name, Personas searches the web for information about you according to a set of categories which it uses to generate a profile like the one above.

I tried with my real name a couple of different ways. Apparently I share my name several other people who have much bigger internet presences than I do - including a golfer and a CEO. The "profile" I get doesn't fit the real me at all. Since the profiles I got didn't seem to reflect me as well as a bunch of other people, I decided to enter "Bridgehead Carbons" as my "Name."

I'm amazed - the largest category is Sports. WTF! Ok so here's my sports-related comment: I can't believe that my hometown Minnesota Vikings actually signed Brett Favre - I may have to root for the Lions this season, because there is no way I can root for that bozo. If they win the Super Bowl with that clown I might be able to live it down. But I don't expect him to play any better with the Vikes than he did with the Jets last year - the hapless Dolphins kept them out of the playoffs with the QB that Farve replaced. For every 3 TD passes, Favre throws 2 interceptions and he's almost as old as I am. The last time he was in the Super Bowl was more than 10 years ago and he LOST.

via Personas - Miss Cellania -

CRC History

The three reference books I use the most often are the Sigma-Aldrich catalog, the Merck Index and the CRC Handbook of Chemistry and Physics. The first one is a catalog and the second started as a catalog. As it turns out, the CRC was also started by a chemical supplier - it wasn't a catalog but was provided as a marketing tool by the Chemical Rubber Company. The first edition, published in 1913, was so popular that it has been revised almost every year since.

The Chemical Information division of the American Chemical Society has an interview with Dr. David Lide , who has edited the CRC Handbook of Chemistry and Physics since 1989. The interview was published in the Fall 2009 Chemical Information Bulletin.

You can also access the interview directly at
http://acscinf.org/docs/publications/Interviews/Lide/2009/CIB2009_61-2_Lide.pdf

Cyclization Reactions and Angelmarin Synthesis

The first total synthesis of (+)-Angelmarin includes some neat cyclization reactions. They started with Umbelliferone which you can buy, and synthesized angelmarin by way of columbianetin.

I'm always curious about where the names of these compounds come from. The systematic names are probably rather cumbersome, so these common names are useful. Umbelliferone is found in plants of the Umbelliferae family - which includes carrots. Also named for plant species, angelmarin was isolated from Angelica pubescens, and columbianetin from Lomatium columbianum.

The first cyclization step is a Claisen rearrangement - three bonds all move in a circle, which causes the allyl group to migrate to the aromatic ring. The resulting ketone tautomerizes to the more stable phenol structure.

After an olefin cross-metathesis to introduce two methyl groups, the next step was in effect a double cyclization. First a stereoselective Shi epoxidation. Then the epoxide is opened during the second cyclization to form columbianetin.

This last cyclization is an an example of a 5-exo-tet cyclization according to Baldwin's Rules for ring formation. The resulting ring is a 5-membered ring. The bond broken to make the new ring is not part of the new ring (exo). And when the new ring is formed, the nucleophile is forming a bond to a tetrahedral atom (tet).
To convert columbianetin into the final product required the formation of an ester. This proved to be challenging - many standard esterification strategies either did not work, or it caused side reactions that destroyed the columbianetin portion of the molecule.

To get around this, they first converted it to a malonate ester under mild conditions. This was reacted with p-hydroxybenzaldehyde and catalytic piperidine to generate the final product by way of a Doebner-Knoevenagel condensation. In effect building the hydroxycinnamate group instead of adding it as a single piece.


Magolan, J., & Coster, M. (2009). Total Synthesis of (+)-Angelmarin The Journal of Organic Chemistry, 74 (14), 5083-5086 DOI: 10.1021/jo900613u

Hubble Deep Field in 3D

According to the Hitchhiker's Guide to the Galaxy:

Space is big. Really big. You just won't believe how vastly hugely mind-bogglingly big it is. I mean, you may think it's a long way down the road to the chemist, but that's just peanuts to space.

I think this starts to give you a hint at how big space is.

link to video via BoingBoing

July Weather: Local vs Global

From AccuWeather:

NASA's Goddard Institute of Space Studies (GISS) has determined that July of 2009 was the second warmest July globally, since records were kept going back well over a hundred years.

The map above compares July 2009 with "normal" - July from 1951 through 1980. Blue is cooler than "normal" and red is warmer. There are some blue bits, but there sure is a whole lot of red - more than enough to compensate for the smaller regions of cooler temperatures.

In fact most of the eastern US was blue in July, with the darkest blue in the Great Lakes region where I live. I know I'll be hearing people say, "Gosh it's been cold this summer. That proves there's no Global Warming!"

The thing about Global Warming is that the Earth warms unevenly - that is one of the things that causes winds. Change the winds and you change the weather. Change the temperature - up or down - and the amount of rainfall and you can have big problems for the farmers.

It's not just an issue of having warmer weather - some people would like that. I have lived in Tennessee and Georgia and I prefer to live in a place that gets snow in the winter, I kind of like the weather as it is. The real issue isn't so much creature comforts but food. Considering all the red in the polar regions, if I lived in Miami I would be a little worried about sea level too.

via AccuWeather.com: Global Warming News, Science, Myths, Articles

Drawing Molecules with SMILES

Lately I have discovered that when drawing 2D or 3D chemical structures, it is often a lot easier to input a SMILES string than to draw it with the GUI. It reminds me of when I first started using Windows (v. 3) - at times I thought it was easier to type a command to tell the computer what I wanted to do instead of hunting through menus and dialogs to find the thing I needed to click.

SMILES is a way of describing a chemical structure on a single line - a LOT like a conventional condensed formula except without the Hydrogens. It is commonly used in database and chemical informatics applications. In an earlier post on Surfactants, I wanted to include the structures of a couple of perfluorinated surfactants. Drawing all 15 fluorines individually was just too tedious, it was much simpler - believe it or not - to type: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(=O)O

Drawing large and complex compounds "by hand" is also a hassle - and in some cases very difficult to get a good looking structure. Fortunately, many on line resources (e.g. Wikipedia, PubChem, ChemSpider) list the SMILES string for compounds like morphine:
Earlier in the summer I decided to install Ubuntu on my laptop in addition to Windows so I could run either operating system. One difficulty I have had in moving to Ubuntu is finding chemistry software to replace the programs I usually use on Windows. It turns out that several of the structure programs that I have been using lately will allow me to input a SMILES string.

One program I have been experimenting with lately is Avogadro - an open source project for building and studying 3D chemical structures. Avogadro is available on both Windows and Linux (as well as Mac), which is pretty convenient for me right now. It is a very nice program, they are at version 0.9.7 and plan to release 1.0 in September.

For drawing 2D structures on Windows I use ChemSketch, available as freeware from ACDlabs. On Ubuntu I have tried several 2D structure programs, none that match up to ChemSketch. One that I have used most is BKChem, which I used for the structure of Morphine above.

The Pentatonic Scale from the World Science Festival

World Science Festival 2009: Bobby McFerrin Demonstrates the Power of the Pentatonic Scale from World Science Festival on Vimeo.

via The Pentatonic Scale - Neatorama

Chemistry Graphics Hassle on Ubuntu

Lately I have been using Ubuntu Linux instead of Windows, and on the whole I think I prefer Ubuntu:

• Ubuntu starts-up and shuts-down faster than Windows
  
• Open Office is faster with Ubuntu (I never use MS Word even on Windows)
• security is much less of a problem (although I do use a virus scan package with Ubuntu)
• FREE SOFTWARE
  
• and the geek factor of using Linux probably appeals to me as well

One difficulty for me has been finding chemistry-specific software to take the place of the Windows programs I am used to using. That situation improved a little bit today.

Avogadro and Ghemical are two programs I have been playing around with for building and doing simple calculations on 3D molecular structures. They both have a window that displays the molecule in 3D, and up until today that has been a problem for me. Frequently the desktop would "bleed through" so I couldn't see the molecule being displayed. Depending on what I was doing it was either inconvenient or a major annoyance. It would be so much easier to do things in Windows. That would involve re-booting the computer and starting Windows - something I try to avoid doing these days.

It turns out the solution was pretty simple, but I'm still a newbie with Linux and it took me a while. If I turn off the fancy graphics for the desktop, the problem goes away. The first time this idea occurred to me I went into the Compiz control panel and didn't know where to even start - and I wanted to be able to turn everything back on again if that didn't work. Compiz has LOTS of settings, I tried a few things without making matters any better.

Instead, what I should have done was go to the System Preferences and select "None" on the Visual Effects tab. Problem solved! The Visual Effects aren't all that important to me, but it's nice that I can turn them on and off so easily.

Now I can spend some time playing around with Avogadro and Ghemical to figure out what they do.

Blue Food Dye Does NOT Treat Spine Injury in Rats

You have probably seen those cute pictures of the blue mice by now. I first saw it on Neatorama, which linked to an article at Wired. Both said in their headlines that a Food Dye was responsible for reducing the damage from spinal cord injuries. To be fair, both sites mentioned in the articles themselves that the actual molecule used was similar to the food dye FD&C blue No. 1, but it was not in fact the dye used in blue M&M's.

The compound used in the Spinal Injury study was Coomassie Brilliant Blue G, which is commonly used as a protein stain for gel electrophoresis and in the Bradford protein assay. As you can see, they are not quite the same - Coomassie has a couple of extra methyl groups, and the substituent on the "top" benzene in this image is different.



The interesting thing to me is how it "works." According to the research article published in PNAS, the initial injury to the spinal cord is followed by a secondary injury. Over time, the area of damaged tissue expands from the original site of injury and the researchers reasoned that this expansion should be preventable.

The P2X7 receptor is a membrane channel that opens in response to increased ATP. In the injuries studied, the traumatized tissue releases a lot of ATP which in turn activates the P2X7 channels causing them to open. This has been linked to the spread of the injury, so anything that prevented the opening of the P2X7 channel could be expected to reduce or eliminate the secondary injury.

The Coomassie Blue acts as an antagonist for the P2X7 receptor. It binds to the receptor but does not activate the receptor - so the channel remains closed. Presumably Coomassie Blue and ATP both bind to the same site on P2X7 and only one can occupy the binding site at a time. Because the receptor is bound to the Coomassie Blue, ATP is unable to bind and activate the receptor. Since the opening of the channel is what leads to the expansion of the injury, keeping it closed will limit this expansion.

This is an exciting discovery, but it is likely to be only the first step. In the study, they treated the spinal cord injuries after 15 minutes. People who suffer spinal cord injuries might be helped by treatment with Coomassie Blue, but it is unlikely that they would receive treatment within 15 minutes.


Peng, W., Cotrina, M., Han, X., Yu, H., Bekar, L., Blum, L., Takano, T., Tian, G., Goldman, S., & Nedergaard, M. (2009). From the Cover: Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury Proceedings of the National Academy of Sciences, 106 (30), 12489-12493 DOI: 10.1073/pnas.0902531106

Blue Man Group video

Blue Thousand and One from Blue Man Group HD on Vimeo.

With the news about Blue Mice lately, here's a cool video from the Blue Man Group.

via The Daily Dish | By Andrew Sullivan

Steven Chu on The Daily Show

John Stewart reveals Energy Secretary Steven Chu's secret identity as a super-hero who combats climate change.

The Daily Show With Jon Stewart	Mon - Thurs 11p / 10c
Steven Chu
www.thedailyshow.com
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Science Tattoos

Here's the neurotransmitter Seratonin from the Science Tattoo Emporium at Discover Magazine

Learning makes your brain happy

Ed Yong at Not Rocket Science writes about a research paper showing a link between learning and thirst in rhesus monkeys. In

Why information is its own reward - same neurons signal thirst for water, knowledge:

he writes:

To me, and I suspect many readers, the quest for information can be an intensely rewarding experience. Discovering a previously elusive fact or soaking up a finely crafted argument can be as pleasurable as eating a fine meal when hungry or dousing a thirst with drink. This isn't just a fanciful analogy - a new study suggests that the same neurons that process the primitive physical rewards of food and water also signal the more abstract mental rewards of information.

As commenter oscarzoalaster puts it:

So there is actual objective evidence that curiosity can be as important a desire as food and water! I feel more normal now!!! Thank you!

If only teaching were so easy.


via Learning makes your brain happy - Boing Boing

Element 112 - Copernicium

Goodbye Ununbium.

Thirteen years after it was first discovered, Element 112 has been officially added to the Periodic Table and its discoverers have suggested the name Copernicium (Cp) in honor of Polish astronomer Nicolaus Copernicus who proposed the heliocentric model of the solar system.

Of course, IUPAC is cautious and the name isn't official yet.

Image: Wikimedia Commons

BBC NEWS | Science & Environment | New element named 'copernicium'

Lipase-Catalyzed Synthesis of a "Green" Surfactant

Surfactants are molecules that lower the surface tension in water. They behave this way because of their dual nature: a long, hydrophobic carbon tail attached to an ionic end, typically an acid or ammonium group. Surfactants are used in a variety of industrial applications including detergents and wetting agents. A number of widely used surfactants are problematic in that they are non-biodegradable and toxic. PFOA and PFOS are perfluorinated compounds (all hydrogens replaced with fluorines) – the fluorines make the compounds very good surfactants, but also very unreactive (and not biodegradable). They are also known carcinogens. SDS and SLES are not so bad, but still they are irritants and contain sulfonate groups that make them not as easily biodegradable as other compounds.

This article describes the synthesis of an alternative surfactant that is both more biologically friendly (non-toxic and biodegradable) and uses “green” chemistry methods that improve the efficiency of the synthesis and reduce hazardous waste products. N-Acyl palmitoyl ethanolamine is derived from two common constituents of biological lipids: the fatty acid palmitic acid and ethanolamine. Like soap, this surfactant is cheap, non-toxic and biodegradable. Like many industrial surfactants, and unlike soap, it is not prone to forming soap scum with hard water.

They used the enzyme Lipase to catalyze the reaction between ethanolamine and a fatty acid (or its ethyl ester). There are two possible products depending on which end of the ethanolamine reacts: either a hydroxy amide or an amino ester. Perhaps not too surprisingly, the hydroxy amide is formed exclusively. Amides are generally more stable than esters, amines are stronger nucleophiles than alcohols, and as the authors point out themselves amino esters with only two carbons between the N and O will rearrange on their own to the more stable amide form. Lipase was chosen because it is a flexible catalyst and the reaction takes place under mild conditions (no strong acids or bases to neutralize at the end).

They investigated three different sets of reaction conditions:

1. reactants in solution, conventional heat source
2. reactants in solution, microwave heating
3. reactants in solid state, microwave heating
   

The enzyme itself was attached to porous resin beads. For the solution-phase experiments, the enzyme and reactants were added to dioxane. For the solid-phase experiment, the reactants were dissolved in a small amount of solvent which was added to the enzyme and then evaporated to leave the reactants as a film on the enzyme-containing beads. Both microwave-heated reactions went considerably faster than conventional heating, and the solid-phase reaction was faster that the solution.

What exactly makes this "green?" While dioxane is not the most desirable solvent, it can be recovered afterwards and re-used. Otherwise, there is little waste. If fatty acids are used as the starting material instead of the corresponding ester there are no waste byproducts (such as ethanol) to separate and dispose of safely, and no strong acids or bases to neutralize. Even the enzyme is re-usable. And the product hydroxy amide is of low toxicity and should be biodegradable as well. If the solid-phase reaction with microwave heating turns out to be practical, it would greatly improve the efficiency of the process by speeding-up the reaction and improving the yield and purity of the products.

Kidwai, M., Poddar, R., & Mothsra, P. (2009). N-acylation of ethanolamine using lipase: a chemoselective catalyst. Beilstein Journal of Organic Chemistry, 5 DOI: 10.3762/bjoc.5.10

Quantum Kitteh

see more Lolcats and funny pictures

Antimony for Good Digestion?!

Scribal Terror has an article on "The Everlasting Pill," which was apparently an item you could buy in the past as an aid to good digestion. It was a small "bullet" of metallic antimony that you swallowed as a purgative agent. Not only that, it was meant to be re-used: once it had passed all the way through your digestive system it could be recovered, cleaned off and used again!

The original source is the Medico-Pharmaceutical Critic and Guide (1907), edited by William J. Robinson, which goes on to say:

This, as Dr. J. A. Paris says, was economy in right earnest, for a single pill would serve a whole family during their lives and might be transmitted as an heirloom to their posterity. We have heard of a lady, says the Doctor, who, having swallowed one of these pills became seriously alarmed at its not passing. "Madam," said her physician, "fear not. It has already passed thru a hundred patients without any difficulty."

And then finishes with this keen observation:

We do not think that the everlasting pill would be popular at the present time.

I wonder why antimony was chosen? Antimony and its compounds have been used in treating parasites, but I don't know it that would have anything to do with the supposed "cathartic" properties of the "Everlasting Pill." Of course, antimony is toxic. According to wikipedia, antimony poisoning is similar to arsenic poisoning, which only makes sense since antimony is right below arsenic in the periodic table. I don't know how much metallic antimony you would absorb through the gut, but I doubt it would be a good idea to use this device.

You can read the original, and many other interesting articles in the Medico-Pharmaceutical Critic and Guide which is available by way of Google Books. This book is out of copyright, so you can read the whole thing for free on line, or download a PDF copy for yourself. As a bonus, you can also search and copy selections on line - which is how I got the quote above. Since the PDF version is just a scanned image it can't be searched or copied so easily.

Image: Wikimedia commons

Scribal Terror: The everlasting pill by way of Neatorama,

Anticancer Compound from a Tumor-Promoter

The title of this article caught my eye because of the irony of designing an anticancer drug by modifying a known tumor promoter. Aplysiatoxin is a tumor promoter, while Compound 1 from the paper is not. In fact, Compound 1 is just a simpler version of Aplysiatoxin: the hemiacetal has become an ether and several side groups have been lost. There are also fewer stereocenters in Compound 1 than in Aplysiatoxin.

First a little background. Both compounds affect cancerous cells the way they do because they bind to Protein Kinase C (PKC). PKC is an enzyme that contributes to a number of signaling pathways within the cell, particularly having to do with cell differentiation, proliferation and apoptosis. PKC's involvement in cellular growth cycles also results in its involvement in carcinogenesis, and it has been a target for developing anti-cancer drugs for this reason.

The curious thing about PKC is that some molecules that bind to PKC activate the enzyme, while others de-activate it. Even stranger, some activators promote tumor formation and other activators do not.

PKC activators have shown some promise for treating diseases such as Alzheimers or AIDS, but their tumor-promoting behavior is a big drawback. Ideally you would want to find a PKC activator that was also non-tumor promoting. Bryostatins fit this description, but the compounds are too complex to be easily made in the laboratory. In nature, bryostatins are made by a coral-like organism but in extremely small amounts. According to Wikipedia, you would need a ton (2000 lb) of bryozoans to obtain just one gram of bryostatin.

Aplysiatoxin binds to PCK as a tumor promoting activator. Compound 1 was designed as a simpler version of aplysiatoxin that might be a PKC activator without also being a tumor promoter. As it turns out, compound 1 shows minimal tumor-promoting activity, and it counteracts the effects of the tumor-promoter 12-O-tetradecanoylphorbol-13 acetate. It's anti-cancer activity as well as it's mode of binding to PKC seems to be comparable to the bryostatins. The authors report that they can make Compound 1 in only 22 steps, which makes it a promising alternative to bryostatins as a potential therapeutic agent.

Nakagawa, Y., Yanagita, R., Hamada, N., Murakami, A., Takahashi, H., Saito, N., Nagai, H., & Irie, K. (2009). A Simple Analogue of Tumor-Promoting Aplysiatoxin Is an Antineoplastic Agent Rather Than a Tumor Promoter: Development of a Synthetically Accessible Protein Kinase C Activator with Bryostatin-like Activity Journal of the American Chemical Society, 131 (22), 7573-7579 DOI: 10.1021/ja808447r

Lord of the Rings Webcomic

I came across "DM of the Rings" on Neatorama the other day and had to read all 155 installments. It's a hilarious web comic by Shamus Young that uses scenes from the Peter Jackson Lord of the Ring movies to imagine a group of Dungeons & Dragons players reenacting the Lord of the Rings. Needless to say the players haven't read the book (or seen the movies), and while D&D is a role-playing game, the players have a hard time staying in character.

The first episode is a good place to start. As a science geek, I particularly liked Schrödinger’s Familiar. If you aren't familiar with the gazillion monsters character might run into, a Lich is a sort of undead sorcerer.

The Chemistry of Firework Displays

photo credit Dori (Wikimedia Commons)

Slashdot has links to some cool articles on the chemistry of Fireworks.

Slashdot News Story | The Chemistry of Firework Displays

Ridiculous Fellows: Amazing Organ Performance

"Ridiculous Fellows," from Prokofiev's "The Love for Three Oranges" orchestral suite. Qi Zhang playing a Yamaha Electone Stagea, which she programmed herself.

Quorum-Sensing Molecules

I was fascinated by Bonnie Brasler's TED talk on Quorum-Sensing, and being a chemist I wanted to know more about the molecules involved. She did put up a slide with structures during the talk, but I wanted more so I did a search on PubMed and found this Perspective written by Brassler and Michael Federle.

My only experience with the notion of a “quorum” is our Faculty Assembly where we sometimes have difficulty achieving a quorum. In order for the meeting to be “official” and for any votes taken to be valid we need to have a minimum number of faculty present, a “quorum.” For bacteria, quorum sensing is the way the bacteria “count” one another. The bacterium releases a particular molecule, called an autoinducer - if there are lots of the molecules, then there are a lot of bacteria. If there are very few autoinducer molecules, then there are few bacteria present. The bacteria has a protein receptor that binds to the autoinducer molecule – so the bacteria can “sense” the presence or absence of autoinducer molecules depending on whether or not the receptor protein has detected any. In this way the bacteria can change their behavior depending on the number of bacteria present, as measured by the number of autoinducer molecules it finds. As a group, the bacteria behave one way when there is a low density of bacteria present and a different way when there is a high density of bacteria present.

In the simplest examples, quorum-sensing allows the bacteria to switch between two different behaviors depending on the number of bacteria present. One example would be the staphylococcus aureus bacteria – at low density they adhere to the surface of the cells of the host organism where they can grow and produce more bacteria. Once they reach a “quorum” there are enough bacteria present to be able to invade the host cells Their metabolism then shifts from producing the proteins that allow attachment to the outside of host cells and starts to produce proteins and toxins that allow the bacteria to enter the host cells. The light-producing bacteria from Bonnie Brassler's TED talk produce light when there are a lot of bacteria present, and stop producing light when there are few bacteria present.

Enough about biology, what about the molecules involved? In this Perspective, two categories of autoinducers are discussed, and one “special case.” Gram negative bacteria produce a type of autoinducer referred to as AHL for Acyl Homocysteine Lactone. Different types of bacteria will have different acyl groups attached to the homocysteine, and only recognize their own type of AHL. Gram positive bacteria do not use AHL's, instead they produce specialized proteins called AIP for AutoInducing Peptides, which consist of a string of 5 to 17 amino acids, some of which may be modified. The two types of autoinducer (AI) are detected by the bacteria when the AI binds to a receptor molecule in the bacteria. The details differ, but when enough AI's are around to bind to their receptors, the receptor causes a change in gene expression in the bacteria, which leads to a different behavior by the bacteria. 

The AHL's and AIP's are species specific: each type of bacteria produces only one AI and only recognizes it's own AI. The third type of molecule discussed is an unusual boron-containing molecule that may have a role for communication between different species of bacteria. The light-producing bacterium vibrio harveyi produces two different autoinducer molecules. The first is referred to as AI-1. AI-1 is an AHL molecule used for communication only among the V. harveyi bacteria. The other autoinducer is AI-2 which, on the other hand, may have a role in allowing different species of bacteria to communicate with one another.

AI-2 is synthesized by the bacteria in three steps from S-adenosyl methionine. The enzyme for the final step in this synthesis is called LuxS and as it turns out the gene for LuxS is found in many different bacteria, which all seem to both make and respond to the presence of AI-2. The implication of this is that perhaps AI-2 serves as some sort of generic autoinducer that allows bacteria to sense not only their own species, but also all other species of bacteria that produce AI-2.

The really interesting thing is that if we understand how bacteria communicate, we can find ways to short-circuit that communication. Many pathogens use quorum-sensing to regulate their virulence. In the example I mentioned earlier about S. aureus, the bacteria depend on reaching a “quorum” before they begin to “invade” the host cells. If their ability to sense one another is prevented, then perhaps their ability to invade the host and cause disease could be reduced.

Federle, M. (2003). Interspecies communication in bacteria Journal of Clinical Investigation, 112 (9), 1291-1299 DOI: 10.1172/jci200320195