YACB - Yet Another Chem Blog

I need to do a blog like I need another hole in my head. Does the world really need another chemistry blog? Probably not. So, why am I doing this? I have no idea. I guess because it's fun? There's so much science out there that seems very impersonal. Perhaps blogging about chemistry allows us to inject our personal views and commentary on current chemistry. My hope is that this blog allows me to present what I find interesting in the world of Organic Chemistry and hopefully inspires people to pursue this wonderful scientific discipline.

ASAP Thursday

The first thing I do when I get into the lab in the morning is make my coffee. The second thing is to see what has appeared on the web journals. I suppose since I'm blogging that I should share with you the articles that catch my eye. Here's a couple from today.

Karl Scheidt has a very nice example of umpolung chemistry catalyzed by N-heterocyclic carbenes in a [3+3] cycloaddition. This appeared on the web yesterday.

Audrey Chan and Karl A. Scheidt, JACS DOI: 10.1021/ja0709167


Interestingly, I was just teaching my synthesis students about the utility of diazo compounds for cyclopropanation and Wolff rearrangements and what appears on OL this morning? A very nice and practical method for the preparation of diazo compounds. This could come in handy.

Muhammad I. Javed and Matthias Brewer, OL DOI: 10.1021/ol070515w

Feline Frolics

I have two cats and they drive me absolutely nuts. Always demanding and always getting in trouble. Today was no different. I had need of some thyme for my spice cupboard, so I snuck out at lunch and stopped by my favorite health food store that has a huge array of dried herbs and spices in bulk. I bought an ounce of thyme and some other goodies and stopped off at home to put them away. No sooner did I drop the bag on the kitchen floor and head to the 'little chemists room' did my biggest pain in the ass, Sam, discover a new toy. Yes, a small little plastic bag of thyme. By the time I got back to the kitchen, he had ripped the bag open and was squirming around on the floor in a big mess of herbs! *sigh* You'd think it was catnip or something, the way he was carrying on. Out of curiosity, I dug up information on the compound found in catnip. It turns out to be nepetalactone. Nothing I could find indicated that thyme contains this terpene. So what was Sam all worked up about? Well, the major volatile constituent of thyme is the terpene thymol. Very different structure than nepetalactone. Although thyme does not contain nepetalactone, catnip does contain significant amounds of thymol. Interestingly, thymol is also used as in ingredient to repel feral cats. Sam sure is odd.

Mechanism Challenge Answered

Tynchtyk, over at Chemist in a Transition State, posted a very interesting transformation and challenged us to propose a mechanism. Here is the reaction.

At first glance, this looks like some kind of reductive amination reaction. However, on closer inspection, you can see that there is one less carbon in the product than the starting material. Furthermore, there are no reducing agents present, only acid (and presumably water). Of course the obvious starting point is to react the secondary amine with the aldehyde to form a cyclic imminium structure. Once generated, this is nicely set up to undergo a [3,3]-sigmatropic rearrangement to transfer an allyl group to the imminium carbon. The resulting formaldehyde imminium product is then hydrolyzed in the presence of water to afford the product plus an equivalent of formaldehyde. The full mechanism is shown below. Notice I am a stickler for showing every proton transfer step! No shortcuts here.

Tynchtyk says this problem appeared in a science olypiad for High School Students in Moscow. I wish our high school education here in the states was up to this kind of challenge.

Thanks, Tynchtyk, nice problem! In the spirit of problem solving, let me pose a new challenge. This is one of my favorite transformations.

Beta Amino Acid Rearrangement

Here's the answer to the mechanism question I posed at the end of the last post. Some have suggested a 4-membered ring intermediate. While that cannot be ruled out, a mechanism that does not include the high strain of a bridged 4-membered ring seems more plausible.

Since this is an aminoacid, it will exist in it's zwitterionic form. Thus, the quaternary ammonium will not be acylated. The carboxylate is converted to a mixed anhydride. Then it undergoes a beta-elimination of the ammonium to open the 6-membered ring. This is followed by an acylation of the resulting amine to form the rearranged lactam.

This reaction was reported by Henry Rapoport (JACS 1970, 92, 5781). He cites an older paper by Ferles (Coll. Czech. Chem. Commun., 1964, 29, 2323.

Update: As liquidcarbon points out in the comments, the free amine of the ring-opened intermediate above would likely be acetylated in refluxing acetic anhydride. Another possible route to the product would involve an intramolecular acylation forming a bridging 4-membered ring, followed by beta elimination. Possible, but I'm not sure how well the bridgehead hydrogen sigma orbital would overlap with the sigma star orbital of the C-N bond.

ASAP Thursday

Some good papers have shown up on ASAP this week. Here's two that rose to the top for me.

First is a contribution from Shu Kobayashi with some very interesting chemistry using chiral Calcium complexes. The reaction he investigated was the Michael addition of glycine derivatives with acrylates. He showed the importance of an enolizable proton on the bis-oxazoline ligand and suggests that the reactive species is a calcium Brønsted base. This generates a chiral calcium enolate that undergoes Michael addition to the acceptor. Subsequently, an intramolecular Mannich reaction ensues to afford pyrrolidines in very high selectivity.

Susumu Saito, Tetsu Tsubogo, and Shu Kobayahsi, JACS, DOI: 10.1021/ja0709730

Organocatalysis is all the rage now, and even we are trying our hand at some. Xiao has just reported a slightly new twist on organocatalysis by carrying out an intramolecular Friedel-Crafts reaction with indoles to form tricyclic compounds. Selectivities are are pretty good in some cases.

Chang-Feng Li, Hiu Liu, Jie Liao, Yi-Ju Cao, Xiao-Peng Liu, and Wen-Jing Xiao, OL, DOI: 10.1021/ol0703130

Cross Coupling of Anilines

A fascinating paper appeared on the JACS ASAP site this morning from Ueno, Chatani and Kakiuchi. They used a ruthenium catalyst to carry out a cross coupling of an aryl amine with a phenyl boronate. What is remarkable is the fact that the transition metal did oxidative addition to an aryl-nitrogen bond. Success of the reaction was dependent on having a chelating carbonyl group adjacent to the amine, however, this is still the first example of oxidative addition to a hitherto unreactive C-N bond.

Satoshi Ueno, Naoto Chatani, and Fumitoshi Kakiuchi, DOI: 10.1021/ja0713431

A Rhodium Thing

Ever since my first encounter with aldehyde C-H insertion by rhodium, I have been intrigued by the possibilities of the acylorganometallic intermediates. In Org. Lett. a nice formal [4+2] cycloaddition appeared utilizing ortho-vinyl benazaldehydes and olefins or alkynes. The reaction proceeds via C-H insertion to form an acylrhodium followed by a migratory insertion to produce a rhodacylopentene. This reacts with an alkene to form the product shown. Chiral ferrocenyl phosphine ligands afforded at least modest level of enationselectivity. If alkynes were utilized, napthol products were produced. Although most yields and selectivities were modest, it is an interesting transformation. It seems to be limited in scope. Without the arene ring cyclization did not take place. Instead the acylrhodium simply reacts with the olefin in a reductive Heck-type process to afford an acyclic ketone.

Ken Tanaka, Daiki Hojo, Takeaki Shoji, Yuji Hagiwara, and Masao Hirano, DOI: 10.1021/ol0704587

Your Road to a PhD

I'd like to call out some of the lurkers who read my blog to come forward and make some comments. I'm curious to find out what influences a student's decision for choice of graduate school in chemistry. So, if you have your PhD, are in a PhD program now, or going to join a PhD program soon, please tell me what was important for your choice of school. Was it location? Science? Stipend? What? Did family issues change your decision? Would you only look at schools on the coasts, or did you look across the middle of the country too? How influential were your undergraduate mentors? What about international studies? This would apply to those from the US going abroad as well as those from outside the US coming to America. And finally, what sources did you use to find graduate programs? Do you put any stock in the web sites that list rankings of graduate programs?

Odeur d'Asperge

Yes, it is asparagus season. I love this vegetable. Raw straight out of the garden, steamed with white wine and garlic, coated with olive oil and roasted on the grill, I can't get enough of it! Of course, for some of us that means plenty of malodorous urinary discharge. Yes, I'm talking about the infamous Asparagus Pee! The culprit - Asparagusic Acid. Derived from valine, this acid is unique to asparagus and appears to be the metabolic precursor to a number of odiferous sulfur-containing compounds. In it's pure form, this colorless solid melts around 76 °C. For those with the enzyme to break it down (~40% of the population) the results appear in the urine usually within 15 minutes of ingestion. Interestingly, not everyone has the ability to smell the satisfying stench, thus complicating studies to determine why some have smelly piss and others do not. I am one of the lucky ones who can both produce copious quantities of metabolites such as methyl thioacrylate (among others) and delight in its pleasing perfume. For those of you deprived of this evolutionary gift, I have sympathy, as you will never truly enjoy the full experience of asparagus season.


(edited 5/8/07, 5:28 pm to fix structures)

Chimie

Please pardon my lack of posts. I'm traveling in France for a couple of weeks and haven't had a chance to write anything. I visited l'École Nationale Supérieure today. I was able to see original research samples from Louis Pasteur. What a treat!

I have returned

I have returned to the US after spending a little more than two weeks in France. I enjoyed food, wine and chemistry during my visit. I was very fortunate to taste some excellent wine including the bottle you see to the right! It was amazing. Was it worth the price? Well, in my opinion, no wine is worth that much, but it truly was exceptional. I am now playing catch up with all the work that was left undone here.

I suppose on a chemistry blog, I should post some chemistry. Among the plethora of fine literature contributions I missed while I was gone was this interesting organocatalytic cascade reaction reported by List.

Jian Zhou and Benjamin List JACS ASAP. DOI: 10.1021/ja072134j

ASAP Friday

A couple of ASAP articles from JACS stood out for me this morning.

The first is an interesting Nazarov cyclization followed by a Wagner-Meerwein rearrangement reported by Alison Frontier. Depending on the substitution, the path of the Nazarov is altered and the reaction is terminated by either a hydride shift or an aryl shift. Interesting paper well worth reading the details.

Jie Huang and Alison J. Frontier, JACS DOI: 10.1021/ja0716148

Mukund Sibi reported a novel organocatalytic method for the conjugate addition of hydroxylamines. The catalyst provides for both hydrogen bonding activation of the substrate and hydrogen bond-directivity for the incoming nucleophile.

Mukund P. Sibi and Kennosuke Itoh, JACS DOI: 10.1021/ja071739c

Summertime Light

I'm back after a bit of an absence. Summer has been very busy and I did take a little time to head back to my home state of Michigan for some camping. One thing I rediscovered was the joy of fireflies. We don't have them where I live now, but I remember the lazy late summer days of my youth chasing and catching these wonderful creatures. They are out in force this year glittering and lighting up the summer nights. Of course this leads to chemistry and not just nostalgic blatherings. As a kid I was fascinated by how the light was produced and we owe it all to a little molecule called Luciferin. In the presence of Luciferase and ATP, an AMP-modified luciferin is produced. This, in turn, reacts with oxygen to produce oxyluciferin in the excited state. Relaxation to the ground state produces the all too familiar orange-yellow glow of the firefly. Nature comes up with some unique ways for males to attract mates, and this is one of the more interesting ones.

Lila's Pasties

Taitauwai, from the Chemistry & Cooking blog, prompted me to post off topic. I guess most organic chemists like to cook, myself included. Anyway, in the comments to my last post I mentioned that I still make my Grandmother's pasty recipe and Taitauwai asked for the recipe.

If anyone has been up to copper country in the upper peninsula of Michigan, you have undoubtedly encountered pasties. These are meat and potato pies that originated in England. During the early 20th century the Keewenau Peninsula was the world's richest source of copper and immigrants from Finland and England mined the ore. The pasty became a staple food for the miners. My grandfather was a copper miner and my grandmother Lila would make these wonderful treats for him to eat at work. The miners loved them because they could hold them in their hands to eat. This is as close to my grandmother's recipe as I can get, although I suspect she used shortening or lard in the crust instead of butter. I prefer them slathered with ketchup.


Ingredients
Serves 8

The Crust
3.5 cups flour
1.5 cups cold butter
1 tsp salt
~0.5 cups ice water

The Filling
2 lb ground chuck or other ground beef
4-5 medium potatoes
4-5 large carrots
1 medium rutabaga
1 large onion
salt and pepper to taste

Method
preheat ove to 375°F

The Crust
Mix the flour and salt. Cut in the butter (I use a food processor pulsing for about 10 seconds) to make a mixture the consistency of lumpy gravel. Add water by the teaspoon and toss just until the dough can be formed into a ball. Wrap with plastic wrap and refrigerate for at least 3o minutes. I like to divide the dough into four balls and slightly flatten them when I refrigerate. This dough should make 8 good sized pasties.

The Pasties
Dice or shred all the vegetables and mix with the meat. Season to taste. Divide the dough into eight and roll them out one at a time into a round oblong shape. Place a mound of the filling on half of the dough and fold over, sealing the edges with a little bit of water and pinche them together. I like to twist and fold the edges up to make the edge a bit more decorative. Place on an ungreased baking sheet and bake for 50-60 minutes, until the crust is nicely browned. Serve with ketchup or butter.

An Alkene Zipper Reaction

Aaron over at Carbon Based Curiosities has recently posted about one of my favorite reactions, the alkene zipper reaction catalyzed by 1,3-diaminopropane and potassium hydride. Most of the time this reaction works great, but it is thermodynamic and has some problems when your alkyne is stabilized by conjugation. Anyway, an interesting paper appeared on the JACS ASAP web site last week dealing with the alkene version of a zipper reaction. It is a very nice contribution from Doug Grotjahn and co-workers from San Diego State University. It utilizes a bifunctional ruthenium catalyst to walk an alkene down the chain until it reaches an alcohol. Once an enol is generated it quickly tautomerizes to the ketone form thus providing the thermodynamic sink for the reaction to fall into. The imidazole ligand on the catalyst was crucial for success and may be involved in the isomerization. A very interesting example of this difficult to accomplish process.

Douglas B. Grotjahn, Casey R. Larsen, Jeffery L. Gustafson, Reji Nair, and Abhinandini Sharma: JACS 2007, DOI: 10.1021/ja073457i

Science Research and Education to get a boost

US House Resolution 2272 will be voted on today and is expected to be passed by the senate on Friday. This is good news. This bill, called the "America COMPETES Act - Creating Opportunities to Meaningfully Promote Excellence in Technology, Education and Science" is a $40 billion three-year bill that will increase funding to the National Science Foundation. But, more importantly, it provides a big boost to an area that is sorely needed here in the US - grade school Math and Science education. I have long thought that the lack of competent people in the physical sciences stems from early on in the education system. As an educator, I find the decline of students in physical sciences alarming. The number one reason I have observed for this decline is a lack of proper preparation before college in math. Students are opting for, shall I say, more wishy-washy biotechnology majors that don't require the math. My suspicions are confirmed by a recent study showing that High School math is the one thing that best prepares students for successful college physical science courses. Another thing I like about this bill is that it requires the President to hold a summit on American math and science practices and to create a Council on Innovation and Competitiveness. If I may speak frankly, our current President has pushed scientists out of governmental advising roles in favor of incompetent buffoons who believe in magic. I am also not complaining about the $22 billion increase in NSF funding. Their grants are way to small now to support a research program.

Tetrakis Talk

{greg the chemist dialing the phone}

{ring}

AA: "Hello, this is Gregory from Alfa Aesar Technical Assistance. May I help you?"

GTC: "Yes, Hi. We have just received our order for 2 g of palladium tetrakis triphenylphospine. The shipment we received is sealed in an ampule but has a dark green color. Can we replace it with some good catalyst?"

AA: "Well, our palladium tetrakis comes in three different colors; yellow, green and brown."

GTC: "But this should be bright yellow."

AA: "We have analyzed our product and chemically it is the same. It should work fine for you."

GTC: "Palladium Tetrakis should be bright yellow."

AA: "I can see that you don't want our product. I will issue a refund and you can send it back to us."

GTC: "Um. Great. Thank you very much."

{click}

GTC: "What the hell? Three different colors? No thanks. Why didn't we order from Strem in the first place?"

{sorry for the poor photos}

And the winner is . . .

Gerhardt Ertl for his work understanding the phenomenon of surface catalysis. In particular hydrogenation, CO2 reduction and more.



Read more about it here: 2007 Nobel Prize in Chemistry

Al is the MAN!

From Senator, to Vice President, to President (well, he won the vote if not the chair in the Oval Office), to Oscar Winner, to Nobel Laureate. No one can say he hasn't accomplished something.

For his efforts in raising awareness about Man's influence on global climate change, Al shares the 2007 Nobel Peace Prize with the Intergovernmental Panel on Climate Change.

The 2007 Nobel Peace Prize

Well Done, Al. I think this prize is well deserved.


Why is this on a chemistry blog? I believe chemistry will be instrumental in solving problems associated with global warming. It already is - from new energy technology to new efficient materials, chemistry leads the way.

IBX (not Irritable Bowl Xyndrome)

I really like oxidation reactions but, for some reason, many students get confused about how they work. It's not really different than any other reaction. It's just electrons moving from one place to another. The problem is that we usually think it is weird to push electrons toward an oxygen at the same time break electrons off of an oxygen. However, in nearly every oxidation of alcohols, this is happening. Of course the requirement is that you have something attached to the oxygen that is more electrophilic. For example, highly oxidized Cr or S or, in the case of IBX or Dess Martin oxidations, I. Well, I saw this interesting paper in Angew. Chem. this week that used IBX to do an interesting double oxidation. It is a nice approach to the saxitoxin family of natural products. I thought I would share the mechanism for your edification. We don't often think about oxidizing past the ketone stage, but under enolization conditions and with the right structural features (beta nitrogen), you can oxidize the alpha carbon.

Iwamoto, O.; Koshino, H.; Hashizume, D.; Nagasawa, K., ACIEE, Early View

Happy Mole Day

Happy Holiday Everyone! I think we all need to take the day off and spread the good word about Avogadro. Is anyone else celebrating?

Gone but not forgotten

Albert I. Meyers
November 22, 1932 - October 23, 2007

I was deeply saddened to hear that Al has passed away. He has been an inspiration to me for a long time. A genuinely nice man, he always encouraged students and colleagues to fulfill their potential. I remember as a young graduate student giving my first talk at an ACS meeting how nervous I was. Afterward Al came up to introduce himself and tell me what a good job I had done. Thanks Al, that did more for my confidence than anything else in my career. Organic Chemistry lost a great one this week. Rest in peace, Al.

Let's Talk Turkey

It is only a couple days away from the Thanksgiving holiday here in America. I love it. A whole day dedicated to stuffing a bird then stuffing yourself full of fats, carbs, and tryptophan. We get to laze around on the couch watching football and make serotonin out of that gobbler. Yes, eating turkey is thought to increase the amounts of this wonderful neurotransmitter and make you sleepy. Of course tryptophan is also the starting material for the production of melatonin, another inducer of drowsiness. Personally I think it is more likely that all the beer and wine being consumed is what leads to thanksgiving day couch potato syndrome. By the way, a recent study reported in the Journal of the Science of Food and Agriculture (that one is on everyone's daily reading list, no?) indicates that red wines have a significant amount of melatonin.

methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphat

Man, the name can't even fit in the title field! Maybe the structure will help. I caught me a nasty bug in my leg that's been growing ever since turkey day and this bad boy is trying to keep it in check. Unfortunately it doesn't look like it's doing a very effective job. I may need to get it in IV form. More and more antibiotic resistant bacteria are making an appearance. Get out there and discover some new drugs. Please! By the way, this one tastes like shit. I am pumped so full of it I can taste it oozing out into my mouth.

Busy as a bee

That is me and why I have not posted lately. I still plan to. Don't give up on me. I'm still finding a few minutes here and there to read an article or two. If only the days were 72 hours long. *sigh*

Anyway, there's lots of buzz about Apple's new Macbook Air. Lots of negative comments going around on the mac forums. I don't understand this. Sure, this computer is not for everyone. Sure, this computer could not replace a primary computer. But let's be honest. This is a computer for travelers. This computer is ideal for me. I can't wait to get my hands on one. In the last five years I can't think of a single time I have used my optical drive while on a trip. Rarely have I ever had to use an ethernet cable while on the road and in the last two years I have never needed an ethernet cable. Who's going to travel with bulky firewire peripherals in their carry on bag? All these arguments against the macbook air are ludicrous. Obviously made by people who don't go on frequent short trips. So I ordered one as soon as they were announced.

I know this is a chemistry blog. So let's talk about chemistry. This is the first laptop with a mercury free LCD display. And the glass contains no arsenic.

A new precatalyst for Heck Reactions

It's a beauty, isn't it? I mean, look at that monster! And it packs 4 palladium atoms per catalyst too. It just appeared in Organometallics (DOI: 10.1021/om7005613). They actually coupled together iodobenzene and styrene. The cool thing about this is that they could tune the reactivity of the catalyst by changing the metal complexed in the middle of the porphyrin. With M=MnCl it took almost 400 minutes for the reaction to complete, but with M=Mg it only took about 200 minutes. Ok, seriously. I don't mean to pick on Bart M. J. M. Suijkerbuijk, Sara D. Herreras Martínez, Gerard van Koten, and Robertus J. M. Klein Gebbink, but I really don't understand what the purpose of this research is. I guess you can get some understanding about the electronic nature of pincer ligands, but no one in their right mind would ever use something like this for a Heck reaction. It is pretty though. It even weighs 10 times more than your substrate. I guess that makes for easy weighing. Let's say you use 10 mol% of the catalyst. You can just use the same mass as iodobenzene and you're good to go.

Something in the air

And it will be in my hands some time today! Just in time for me to take it on the plane tomorrow. Yes, the new Macbook Air is a perfect travel partner. I'll give you my review of it soon.

The Air Has Landed

The good, the bad and the ugly. Well, there's absolutely nothing ugly about the macbook air. It's absolutely gorgeous. Thin thin thin. It is much sturdier and lighter than I expected. It feels weightless. HUGE plusses for design and portability. The keyboard feels great. The screen looks fantastic. You can see some comparisons with my 15" macbook pro. It's definitely smaller by a long shot. I love the lighted keyboard. It seems to function even better than my MBP.

As for performance, it's not the quickest horse out of the gate but it certainly wasn't as pokey as I expected based on the reviews out there. For most major tasks - keynote, pages, word, web browsing - it performs just fine. It even compared with my 2.0 GHz MBP in iphoto - granted with far fewer photos in the library. I don't need anything more intensive really, so this is good.

Did I mention it was thin? I can hardly tell it's in my bag when I carry it around. That's exactly what I need for traveling. For this reason it is fantastic for me.

One thing I noticed was that the charger works either way it is plugged in. I know some people have complained that the cord bends too much when plugged in if the plug is behind you. No worries. You can just attach the connector the other way around and no more 180 cord bending. The one negative thing that I would say is a real fault is the slow slow battery charging. I just noticed that it is only 35% charged after an hour plugged in when it was down to 15%. Apple, without a replaceable battery, you need to do better than this! Hopefully this can be resolved with a software update soon.

Overall I give this one Three Thumbs Up!

Depressed?

Depression seems to be the illness of the 21st century and for more than 15 years Selective Serotonin Reuptake Inhibitors have been the pill of choice. Yes, the number of prescriptions of these antidepressants (effexor, prozac, seroxat, etc) has increased exponentially. So much so that these drugs being excreted by humans is negatively affecting wildlife. With all the billions of dollars being spent on these drugs has anyone ever asked the question, Do they help? Well, psychologists at the University of Hull have reviewed the results of about 50 clinical trials. Their conclusions? SSRI antidepressants do not really seem to provide a benefit to most people as compared to placebos. Sure, there's a little evidence that they help to some extent the most severely depressed, but the large majority of the millions of prescriptions really are doing nothing but causing gender confusion among the fish and frogs.

Drink your pharmaceuticals

An interesting report on the state of our drinking water appeared today on CNN. We've often heard of municipal drinking water being polluted with things like lead, MTBA, pesticides, etc. But this report talks about finding lots of different pharmaceuticals in our drinking water - everything from sex hormones to antibiotics to, yep, antidepressants. Actually in some places more than 50 different drugs were detected. While the amounts are very tiny (ppb or ppt) very little is known about the effects of even small amounts of drugs over a long period of time like decades. I think Dr. David Carpenter says it best:

"We know we are being exposed to other people's drugs through our drinking water, and that can't be good," says Dr. David Carpenter, who directs the Institute for Health and the Environment of the State University of New York at Albany.

To be or not to be

Oh, I know I've been ignoring this blog. I wondered if anyone even read it. It has dropped down on my list of priorities. But now I read over at Homebrew and Chemistry that my blog is being chopped from at least one person's reading list. I suppose I should have seen it coming. The question is, will this inspire me to reinvigorate Carbon Tet or should I let it die in quiet peace? Perhaps if people leave a comment or two it might help me make up my mind.

Atomic Noodles

Ok, I hear the voices from my last post and have decided to commit to trying to keep this blog going. My goal is to make sure I publish a post at least every week, if not more often. I've realized it doesn't have to be a chore and that I don't have to always have some latest greatest chemistry from the just uploaded ASAP's. I can do some fun stuff. I can even borrow from other stuff on the web. Why not? People do that all the time on their blogs.

Ok, then. How about a little bit of video? I know it's not directly chemistry, but it does fascinate me. From "The Ring of Truth: Atoms," here is Chef Kin Jin Mark pulling noodles.

Largazole and Histones

I have a certain affection for things that affect epigenetic regulation. Hence my interest in a class of enzymes called histone deacetylases (HDACs). These are zinc-dependent hydrolases that cleave the acetate group off of the lysine residues on the N-terminal tails of H3 histones. The bottom line is that deacetylation of these proteins that DNA wraps around turns off gene expression. In some cancers, tumor supressor genes are turned off and application of HDAC inhibitors turns them back on causing the cancer cell to die its normal death. That is a simplistic description. It is actually much more complicated than that. A simple animation of this is provided on the Methylgene web site.

In January, the Luesch group from Florida reported (J. Am. Chem. Soc., 130 (6), 1806 -1807, 2008. 10.1021/ja7110064) the isolation and characterization of an antiproliferative natural product called largazole. They subsequently synthesized it and discovered it was an inhibitor for HDACs (J. Am. Chem. Soc., 130 (26), 8455–8459, 2008. 10.1021/ja8013727). The synthesis is pretty efficient encompassing 8 steps with an overall yield of 19%. That's not too bad. Andy Phillips, in Colorado, has just published another 8 step synthesis and have confirmed the Leusch findings (Org. Lett., ASAP Article, 10.1021/ol8013478 ). In addition they have done some NMR conformational studies to show the solution structure of this interesting molecule.

What I find very interesting about this story is that the compound looks so very similar to cyclic peptide HDAC inhibitors developed in Japan (FK228, link to PDF). The sulfur gets buried into the active site pocket to bind the catalytic zinc while the cyclic structure binds to the surface of the enzyme. Both are necessary for the nanomolar level of inhibition of Class I HDACs that are observed for these compounds. Knowing the structure of FK228, I would have immediately made the connection between largazole's antiproliferative effects and HDAC inhibition. The original isolation paper does not speculate on that which makes me wonder if the Leusch group only made this connection later. I presume so.

The way this story has unfolded reminds me that I need to search more broadly when I am looking for HDAC inhibitor structures. Just searching on the keyword 'hdac inhibitor' is not enough and probably misses some compounds that people haven't yet connected to HDACs.

What do flamingos, Cheetos and Quantum Chemistry have in common?

The vibrant colors of flamingos and Cheetos are both the result of related carotenoid dyes. Carotenoids (named for the vegetable in which they were first found!) are based on a linear conjugated diene skeleton, and provide nature with many colorful accents. Canthaxanthin, for example, is fed to captive flamingos to produce their characteristic pink color (a similar pigment found in brine shrimp does the same favor for wild flamingos). Astaxanthin is responsible for the characterstic color of lobsters. Canaries, whose signature color is a greenish yellow, can be turned red if they are fed paprika during their molt. The new feathers will grow in orange-red.

If you're tired of only changing the color of your hair, you can try for a pumpkin look for fall. The compound that gives this class of vegetable pigments its name - β-carotene - when consumed in large quantities by humans, will turn them orange. [Really, but don't try this at home! It was observed clinically in Britain during WW II when food shortages led some people to include large amounts of carrots in their diets.]

If you thought the bright color of Cheez-Whiz and Cheetos was artificial -- it's not. Bixin or annatto, a natural pigment used for centuries, is the source of that unforgettable orange. Researchers have recently elucidated the biochemical pathway for the synthesis of bixin and are pursuing genetic engineering approaches to its bulk synthesis in tomatoes [Florence Bouvier in Science, 300:2089-2091, June 27, 2003].

What does this all have to do with quantum chemistry? A very simple quantum mechanical model, the particle in a one-dimensional box, can be used to predict the color of conjugated dyes.

Cranky Numbers: From the 3rd grade to Fermat's Last Theorem

What's the connection between 3rd grade math and Fermat's Last Theorem? My 3rd grader comes home with problems that ask him how many ways he can write a number, such as 4, prompting him to list such expressions as: 1+3, 2 x 2, and 8÷2. If you restrict the list to sums of non-negative integers, the list is short and finite: 0+4, 1+3, 2+2, 1+1+2, 1+1+1+1. The number of sums in the list is called the partition number; the fourth partition number is thus 5. A patient 3rd grader (if such existed) could find the partition number of any integer. Partition numbers are handy if you are a 3rd grade teacher making up problems to occupy your students or a particle physicist.

If you looked at a list of partition numbers (the first 20 are: 1 2 3 5 7 11 15 22 30 42 56 77 101 135 176 231 297 385 490 627 more), you might notice that starting with the 4th partition number (5) every 5th number is divisible evenly by 5. Beginning with the 5th number (7), every 7th number divided evenly by 7. Perhaps not surprisingly, every 11th number after 11 is also divisible evenly by 11. The pattern ends there, but not the mystery. Indian mathematician Srinivasa Ramanujan recognized the patterns almost 100 years ago, but it took almost 40 years before Freeman Dyson explained them by inventing a function which he called the rank. Dyson's rank only explained the 5 and 7 patterns, roughly another 40 years would pass (is there a pattern here?) before the invention of the crank would account for the 11's.

As it turns out, there are more sequences buried in the list of partition numbers, you just have to know where to find them (a pattern based on those divisible by 13 begins with the 111,247th partition number). It also helps to have some of the techniques in number theory developed by Andrew Wiles to prove Fermat's Last Theorem. A proof that such patterns will exist for any prime number larger than 3 was published this year by Karl Mahlburg, a graduate student in math at the University of Wisconsin.

Extract DNA in your kitchen

When my kids think of DNA, they think of the classic picture of the double helix. But what does DNA really look like? A lot depends on how you look at it, and since most of us don't have a good scanning tunnelling microscope at home, we can't get pictures that look like this one from Lawrence Berkeley Labs.

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With a bit of patience, you can extract DNA in your kitchen, and see what the long polymer strands look like in the aggregate! The Genetic Science Learning Center at the University of Utah has developed a protocol for extracting DNA from split peas. Last summer my kids and several of their friends spent a morning in our kitchen pureeing peas and extracting the DNA. The white threads at the top of each test tube are the DNA. A great rainy day project - even if you don't have kids.

Building better ice cream and popcorn - who says physical chemistry is useless?

Physical chemistry, which I teach, has a certain reputation among chemistry majors: as difficult, dull, mathematically intensive, time consuming. There is even a bumper sticker that says "Honk if you passed p-chem!" When you are looking at the Maxwell relations in thermodynamics, it seems hard to imagine that p-chem has any impact on your daily life at all. But in reality, researchers at Purdue University are hot on the trail of better microwave popcorn and using physical chemistry to do it. [See Role of the Pericarp Cellulose Matrix as a Moisture Barrier in Microwaveable Popcorn; Agung S. Tandjung, Srinivas Janaswamy, Rengaswami Chandrasekaran, Adam Aboubacar, and Bruce R. Hamaker; Biomacromolecules].

Unpopped kernels in your popcorn are a pain, particularly when your kids pick them out and leave them in the living room! It turns out that unpopped kernels are even more of a problem in microwaved popcorn (is there any other kind anymore?). The key to getting popcorn to pop is is the structure of the outer hull (the pericarp), which is made of a biological polymer (which is why this was published in the journal Biomacromolecules). Pericarps in which the cellulose polymers exhibit a strongly crystalline structure pop better. The researchers used differential scanning calorimetry and x-ray crystallography to study the pericarp.

Prefer ice cream with your movie? Erich Windhab, at the ETH in Zurich (where Einstein once worked), used physical chemistry and physics to figure out how to make a smoother, richer ice cream - with fewer calories. You can now buy ice cream made with this process (Edy's Grand Light where I live). [See the article by Robert Kunzig in the June 2004 issue of Discover]