Chemistry Blog

You are getting sleepy…

Just dropping a note to check out the new Ambien CR commercials that are playing on American television (not sure if they’re playing in other countries). You can find the commercials by clicking on the link entitled “Watch the Clips” on this webpage.

For those who are not aware, Ambien (now sold generically as zolpidem tartrate) is a pharmaceutical manufactured by Sanofi-Aventis that is used to treat bouts of insomnia. The controlled release (or “CR”) formulation is a combination of two drugs where one puts you to sleep immediately and the second signals your body to stay asleep.

Ambien’s generic version was recently approved by the FDA for sale in the United States. In many of these cases (as patent life expires) pharmaceutical companies will try to “improve” their formulation to extend the life of a patent (by filing another application). In this particular case, Sanofi was awarded a US patent on February 4, 2003 for a “controlled-release dosage forms comprising zolpidem or a salt thereof” (US patent #6,514,531). I’m guessing that Ambien CR is Sanofi’s attempt to prolong the life of their “Ambien” drug.

At any rate, Ambien CR’s new add campaign is being hailed as a revolutionary marketing strategy, predominantly because the commercials are simple, entertaining and urge you to want to check out their website without actually mentioning the drug they’re marketing. Truly brilliant.

Posted in chemistry videos | No Comments »

Halogen Bonding

Some of you may be familiar with the term “halogen bonding”. In analogy to hydrogen bonding, this weak interaction occurs between an electron donor, such as nitrogen, and a halogen (Cl, Br, I). The halogen acts as an electrophile.

This is possible because the halogen has a region of positive partial charge at its tip, the so-called sigma-hole, as shown by calculations (doi:10.1007/s00894-006-0130-2). The group of Resnati and Metrangolo in Milan have used this interaction to construct a variety of polymeric chains and networks for crystal engineering. As they discuss in their current Science paper (doi:10.1126/science.1162215), it also plays an important role for drug design, which I am particularly interested in. Many drugs on the market are halogenated aromatics. The exact role of the halogen for binding is not always known, since often it was introduced in order to tune the hydrophobicity of the compound. I suspect that in many instances, halogen bonding to a backbone carbonyl oxygen could be of importance.

Clearly, more work is required to further investigate halogen bonding in a biological context. If people want to incorporate this kind of interaction into rational drug design or crystal engineering, good quantitative models will be needed.

Posted in general chemistry | 11 Comments »

ACS Day 4: New Uranium (VI) Chemistry (non uranyl)

Hayton, from Santa Barabara, presented his recent work with uranium (VI) compounds. The chemistry of Uranium (VI) is dominated by the formation of Uranyl (UO₂)²⁺. However, the Hayton group was able to synthesize and fully characterize U(O^tBu)₆ (1). The compound was reacted with aryl-alcohols in the hope of producing U(OAr)₆ (2) compounds, shown below.

Unfortunately, due to the presence of lithium from earlier steps he prepared (3) and after doing a better job ridding his reagents of lithium produced (4).

The work highlights the difficulty in synthesizing stable uranium (VI) compounds, but perhaps if they didn’t use the electron withdrawing fluorine groups with their arylalcohols they might better stabilize the U⁺⁶.

More Info: Synthesis and Characterization of Three Homoleptic Alkoxides of Uranium…

Mitch

Posted in ACS, nuclear chemistry, synthetic chemistry | No Comments »

First Day of Classes

Regardless of wheter you’re an undergrad, grad student, professor, industry worker, retired or anyone else who reads this blog, I wanted to wish everyone a happy start to the new school year!  Though I openly admit I am tired of University life, there’s something refreshing about the first day of classes.  As a scientist, I’m naturally curious to know what you all see on your campuses the first day of classes.  I now present my experience in the first 20 min of the 2008-2009 academic year:

WARNING: MY CAMPUS IS HEAVILY GREEK

• The want-to-be sorority girl wearing shorts that are, well, just a little too high (these ones are sort of difficult to pick out, but they make you laugh).
• Two random guys talking about how [the University] has “a good shot” at winning a national championship this year (in football)
• The cookie cutter sorority girls complimenting each other’s shirts (“Your top is so cute!” I heard that 3 times between the 200 yards from where I park to where my research building is located)
• The freshmen girls decked out in Greek letters (shirt, flip-flops and tote bag) wearing huge sunglasses (it’s cloudy today)
• The fraternity guys wearing either bright, lime green or pink shirts while donning sunglasses (believe me, it’s incredibly cloudy today)
• I had to register my laptop 3 times with the University network even though I’ve been using the same computer for the past 3 years
• A full parking lot by 7:45 am (classes start at 8 am)
• People in suits passing out bibles
• The poster people in the student union (campus center)
• The only day you’ll actually see most professors dressed nice
• The only day you’ll actually see most professors on campus before 9 am
• The people at Starbucks were actually nice this morning (though somewhat groggy)

Posted in Uncategorized | 3 Comments »

ACS Day2: Graphene Ribbons

Dresselhaus of MIT did a review of her many years in carbon nanostructures. She also presented some of her recent work with different types of graphene ribbons. Specifically, for the zigzag case shown below the electronic structure will be highly metallic while the armchair graphene will have a more traditional semiconductor electronic structure.

From graphene to nanotubes to graphene again and now nano ribbons what’s next for the nanostructure field? Gold nanotubes anyone…

More Info: Crystalline Graphene Nanoribbons (thanks to Excimer)

Mitch

Posted in ACS, materials chemistry | 2 Comments »

ACS Day1: New Actinide Solvent Extractors

The ability to selectively extract actinides out of nuclear waste remains a hot research topic. Today Hancock, from Wilmington, gave a presentation on several tetradentate ligands that bind to actinides more strongly than other smaller metals. The systems he investigated are shown below.

The PDA system was highlighted for its rigidity, fluorescent potential, and the size of its cavity. Some formation data below.

These types of systems look promising and are a nice upgrade over traditional old-school extractors like tributylphosphate(TBP).

Much of the talk was covered in this recent paper: Affinity of the Highly Preorganized Ligand PDA…

Mitch

Posted in ACS, nuclear chemistry | 1 Comment »

ACS Endorses Quackery

I’ll be attending the ACS-Philadelphia conference next week. One of the sessions sponsored by the Environmental division is called “New Energy Technology” on Wednesday morning out at the DoubleTree-Maestro B. The title implies itself to wonderful talks discussing frontiers in applied energy chemistry. Unfortunately, the session is completely dominated by the left-field cold fusion people. A list of the talks are shown below

• Cold fusion in light of green chemistry (Jan Marwan)
• Low energy nuclear reactions research: 2008 update (Steven B. Krivit)
• Overview of LENR research: Critical steps on the pathway to technology(Michael Charles Harold McKubre)
• Macroscopic quantum dynamics and the problems of loading in Pd-H(D) systems (Antonella De Ninno, Emilio Del Giudice, Antonio Frattolillo)
• CR-39 studies of Pd/D codeposition (P. A. Mosier-Boss, Stanislaw Szpak, Frank E. Gordon, Lawrence Forsley)
• Study of the nanostructured palladium deuterium system (Jan Marwan)
• Sonofusion from deuterons to helium (Roger Stringham)

My feelings on cold fusion research have been stated previously here: The difference between cold fusion and cold fusion

It would be in good taste to attend the session, and let them have the opportunity to present their research, but I question whether I could sit through it. If you find yourself bored on Wednesday morning and ready for a lively debate, I’d recommend attending this session.

P.S. Expect dispatches from the conference. I’ll be covering a wide slice of the sessions with my new ACS press-pass: ACS-2008 Philadelphia.

Mitch

Posted in ACS, nuclear chemistry | 8 Comments »

The Interface of Rose Bowls and Priestly Medals

Few equate chemistry with (American) football.  You could imagine my surprise to see that this year’s chemistry SURP program featured a guest lecturer that would cover the symbiotic relationship between ethics and athletics.  My freshman year of college, I had a philosophy professor that taught Aristotle’s Nicomachean ethics through a football analogy, but that’s the closest I’ve ever made a connection between scholarly aptitude and a rugged manly sport.  After getting “special permission” from the department to attend (I’m definitely not a SURP student), I got the rare opportunity to sit in the same room with a prominent sports figure—the head coach of our University’s football team.

Those who know me will probably know which coach I’m talking about, but for the sake of anonymity, I’ll simply refer to him as “Coach.”  Arriving a few minutes late, “Coach” darted through the door and up to the head of the classroom avoiding eye contact.  Truthfully, I saw no difference between his social manner and most other profs (no smiling, reasonably polite yet focused).  Rather than stand in a traditional lecturing position, Coach elected to sit at eye level with the 20 of us (some of whom were there to bombard him with football questions).  He started the discussion by saying, “I’m not really sure what I’m supposed to talk about, but this’ll be pretty informal.  I figure I’ll talk about ethics from my perspective then answer any questions you guys have, except about the football team.”  That was a pretty reasonable request because if I were hypothetically in a room with Terry Francona, he probably wouldn’t want me to ask why he hadn’t benched Manny Ramirez weeks ago.

The crux of Coach’s discussion was two-fold and actually quite simple: (a) goal setting is paramount to excellence and (b) you have to learn to overcome anything that gets in the way of preventing you from reaching your goals.  He offered up this story:

“I asked one of my wide receivers, ‘what’s your goal for the year.’  And, he says, ‘Coach, I want to catch 50 passes this season.’  That’s not a goal.  That’s an end result.  His goal should be to push himself to become a better player so that you are able to catch 50 passes…Now, if you mix distractions into the equation, you’ve introduced another hurdle to cross for you to reach your goal.”

At one point, Coach drew on King’s street sweeper quotation.  For those of you who are not familiar here it is:

“If you are called to be a street sweeper, sweep streets even as Michelangelo painted, or Beethoven composed music, or Shakespeare wrote poetry. Sweep streets so well that all the hosts of heaven and earth will pause to say, ‘Here lived a great street sweeper who did his job well.’”

Coach’s overall message?  Give it everything you have and you can sleep easy at night knowing you did your best.  “It” in his case is defined as hard work on the football field.

That night I tried to distill away the football and civil rights references to understand how I could apply Coach’s lessons to my job/education as a chemist.  I asked myself, “should I focus on making sure I have 25 papers before I leave grad school (I know, it’s a dream) or should I spend more time on developing my skills to be the best chemist I can be so that I can give my best at trying to get 25 papers before graduate school.”  Ultimately I arrived at the later option. 

I realize that while I do give an honest effort on most days, there’s always room for improvement.  I argue that the blogging, literature searching and even podcasts I listen to are making me become a smarter scientist.  But, do I really need to be listening to the new Tantric album while I’m trying to think my way through a reaction, for example?  Should I eliminate my distractions (including occasional, social interaction) and maintain focus at all times?  When do you call it a day?  8 hours?  13?  20?  When is the job truly done?  How do you correctly balance work and family/personal time?  Perhaps I don’t have a good objective answer to any of these questions.  But I’ll tell you that my lab bench and desk are now the cleanest and distraction-free they’ve been in a while.  Let’s see how long this lasts.

P.S.  I definitely plan on seeing the new X-Files movie this weekend (I own an “Asian Collectors Edition” of seasons 1-9).  It appears to have bad reviews, but I’m a diehard fan, so I’ll go see it anyway.  How about you?

Posted in ethics | 6 Comments »

Biology in 4D

Hello everyone. Mitch has asked me to contribute to this blog. This may be somewhat difficult as I am a biophysicist which leaves the topic of this blog as the one branch of science left out of the name of my field. Perhaps it would be better if I refer to myself as a biophysical chemist (or would that be physical biochemist? chemical biophysicist?)

Anyway, as the token biologist, I wanted to bring your attention to a commentary in Cell (doi:10.1016/j.cell.2008.06.013) describing the role of Pixar-style computer animations in the future of biology education. Although the article is an interesting read, what I really wanted to show you all is the author’s website (www.molecularmovies.org) which houses a collection of these animations. (Warning: visiting this site can be hazardous to your research productivity)

There are tons of other really great computer animations on the site (though some are not so great in terms of explaining things. Alas, the one video related to organic synthesis falls into the not-so-great category). My personal favorite is the movie on apoptosis (programmed cell death), which features one of my favorite protein complexes, the apoptosome (or as I like to call it, the seven-membered ring of death).

Now, as a biophysicist, I think that these videos are great because they illustrate some very important concepts in biology. The apoptosis video shows how many processes in biology resemble overly complex Rube-Goldberg Machines. Other videos on the site, especially those by Drew Barry, offer a glimpse into an important field of research: protein dynamics. Chemists are used to thinking of catalysts as fairly static entities. Sometimes a catalyst can be as simple as a surface that acts binds a reactant and primes it for subsequent reaction. In contrast, the catalysts in biology, enzymes and ribozymes, are rarely static. The video on DNA replication (video available at the WEHI website) shows the dynamic nature of these biological catalysts. The animation shows the E. coli replisome, a large multienzyme complex, as it copies DNA. The components of this complex have a number of different enzymatic activities that all need to be synchronized and coordinated in order for replication to proceed. Despite all these complicated interactions, the E. coli replisome proceeds at a rate of about 1000 nucleotides per second and with an error rate of about 1 per 10⁹ nucleotides.

Of course, one has to remember that these videos are animations, not realistic simulations. While they are based on empirical results (e.g. crystal structures, biochemical assays, single molecule experiments), the animators do take some creative liberties with the videos. For example, I doubt anyone has observed buzzing and clicking sounds that accompany Brownian motion and enzyme catalysis in many of these videos. Indeed, the animators (with good reason) don’t show two concepts that are becoming increasingly important in understanding biological dynamics: the stochasticity of events in the cell (e.g. polymerases don’t move along at a constant rate) and the very crowded environment of the cell.

Most significant, however, is that while many of these videos depict the dynamics of various enzymes, not much is known about the actual motions of these enzymes and enzyme complexes. When biologists discuss conformational changes, these protein movements are often identified by looking at static “snap-shots” of an enzyme in two different stages of a reaction. Rarely are the kinetics of the transition measured directly, and the techniques that can directly observe conformational changes (e.g. Förster resonance energy transfer) give limited spatial information. Furthermore, the single molecule experiments that give arguably the best kinetic information about enzyme catalysis and protein motion often have limited temporal resolution (it’s hard to go below the millisecond time scale). Computational methods (e.g. molecular dynamics) can give detailed videos of molecular motion with both high spatial and temporal resolution, but modern computers can simulate only tens of nanoseconds, orders of magnitude below the timescale of most large protein motions. NMR spectroscopy has the advantage of being able to access a large range of time scales, but NMR measurements are limited to small systems and can access only dynamics of an enzyme in equilibrium. Being able to somehow synthesize and connect the information from timescales ranging from bond rotations and vibrations to conformational change and allostery is a tough task, but doing so may offer huge insights into the fundamental chemical and physical principles governing enzyme catalysis. Recent attempts to do so (Henzler-Wildman et al. 2007, doi:10.1038/nature06407, doi: 10.1038/nature06410) have been very promising, though there is still much work left for us biophysicists.

Posted in chemical biology, chemistry videos | 1 Comment »

BOSS XI

Last week I had the opportunity to attend the Belgian Organic Synthesis Symposium (BOSS) in Ghent. This included 4-5 lectures a day, poster presentations and of course sightseeing! The speaker list comprised big names, such as Baran, Carreira, Denmark, Du Bois, Fürstner, Hartwig, Shibasaki and Trost. I’m not going into detail about the lectures, as this seems to be covered in Tot. Synth. You can see the full programme here.

I can say as much: the conference was really great, if you ever get a chance to go there, do so! Everything was well-organized, most of the lectures were highly interesting, and so were the posters. In addition, Ghent is a beautiful town that is well worth a visit.

Posted in Uncategorized | 5 Comments »