I remember being asked once in graduate school by an undergraduate if I had instant recall of all of the detailed information on proton chemical shifts for all of the various chemical environments out there. While I didn't laugh – to be honest, while I remembered the general trends, there was no way I could rattle anything else off at the drop of a hat0 – it reminded me of the disconnect that I occasionally felt while in graduate school for chemistry. I never felt like much of a chemist – the aspect to chemistry that really distinguishes it from the other natural sciences1, synthesis, was something I did sparingly once I finished my undergraduate organic chemistry sequence. Grad school was focused on the area of solid state nuclear magnetic resonance (NMR) spectroscopy – a topic which gets minimal mention, if any, in most undergraduate curricula in the natural sciences. Worst of all2, I worked on proteins while in grad school – given the occasional bit of heat that can get generated come October depending on who's gotten the call from Stockholm, having any connection to biochemistry can make one become the token biochemist who tries to humbly explain why the Nobel went to someone who may actually have done some pretty decent work and is not, in fact, an unwashed lump of pirate scum.
However, being firmly ensconced between biology, chemistry, and physics is actually a really great place to be in my books. The biggest advantage3 is that I can lament the biological understanding of chemists and physicists, the physics blindness that chemists and biologists exhibit, and the appalling lack of chemical intuition that biologists and physicists demonstrate. However, I try not to do this too often, as I find it obnoxious and mostly only of use while at happy hour tweaking people's noses about this sort of thing. I of course hear the “jack of all trades, master of none” refrain, so I figure it all balances out in the end. While in grad school, in addition to playing with a couple of proteins via solid state NMR, I also had the opportunity to dip my toes into the uses of solid state NMR in investigating polymorphism in organic compounds, coordination chemistry complexes, a few discussions on possibly utilizing it for various materials, and the standard hijinks with cryogenic liquids that are part and parcel of every magnetic resonance laboratory (LN2 chilled vodka has a certain ambience to it).
So, given that NMR is a wonderfully interdisciplinary technique, and because I feel like rambling on about certain applications thereof given my past research interests (temporarily on hold while I get accustomed to things in the new laboratory where I make my home), I feel compelled to start what I suspect will be an infrequent but persistent habit of discussing various aspects of NMR dear to my heart. Now, when I think of NMR, I think of many things4, but among the first is the Hamiltonian which describes the plethora of interactions possible during an NMR experiment:
Htotal = HZeeman + HRF + Hdipolar + Hchemical shift + Hquadrupolar + Hhyperfine + Hscalar
The first term, HZeeman, is the interaction between the nuclear spins and the static applied magnetic field of the magnet iself, while the second term, HRF, is the interaction between the nuclear spins and the varying applied magnetic fields – aka the radiofrequency pulses – that compose the NMR experiment. The next term, Hdipolar, is composed of the various dipolar interactions that are at play in between the nuclear spins. This can be divided into the homonuclear and heteronuclear dipolar interactions. The chemical shift component, Hchemical shift, appears next, describing the shielding the nuclear spin experiences from its local chemical environment. The quadrupolar interaction, Hquadrupolar, crops up at this point, describing the interaction of the nuclear spins with the local electric field gradient for nuclei whose spins are equal to or greater than 1. The following term is the hyperfine interactions, Hhyperfine, where the nuclear spin is interacting with an unpaired electron. The last term is the scalar coupling (or J-coupling), Hscalar, which is the indirect through-bond interaction between two nuclear spins. Now, one can rewrite and manipulate this Hamiltonian's form as one sees fit or finds convenient – one could include the scalar couplings in the dipolar interaction term, for instance. Here, the off-diagonal matrix elements of the tensor describing the dipolar interaction would account for the scalar coupling and other effects.
Depending on what one does, these interactions may be nonexistent, attenuated, or averaged out. Sometimes you want to reintroduce these interactions (the excellent work on residual dipolar couplings is an example of this), other times you want to quench them (for instance, the interest in developing heteronuclear decoupling methods in solid state NMR of organic solids, including proteins and other biological samples). Obviously, if one never works with paramagnetic samples, fretting about the hyperfine interaction term is likely not the best use of one's time. And, well, if you do MRI, you may not have to think too much about chemical shifts in certain cases.5
Anyway, now that I've bored everyone with some elementary ramblings on NMR in anticipation of more interesting posts later on, I think I'll end this section. I do intend to keep writing about things of general scientific interest, my occasional thoughts about other things that cross my mind in related veins, and hopefully tweaking a few noses. I will eventually get the blog list and layout figured out in due time, but don't hold your breath. Any recommendations or suggestions - whether it be blogging technicalities or about the content - will be appreciated (although not necessarily followed up on). Hope everyone who's reading this had a delightful holiday season and New Year's!
Notes:
0.) I do have pretty good recall when it comes to the 13C chemical shifts of interest for amino acids, and a lesser level of recall when it comes to the 15N chemical shifts. Of course, that's from years of interpreting NMR spectra, not because I made any specific effort to stash them in my memory.
1.) At least in my opinion. Your perspective may differ on this, of course. I've made the point elsewhere that chemistry is all about structure, reactivity, and synthesis (see here ) and that instead of having grad students synthesize something interesting, biochemistry has model organisms synthesize the sample of interest (GFP, for instance) to allow the biochemist to focus on something more than just preparing the sample. This is a far longer, more subtle, and more complicated argument than I am giving justice to here – perhaps I will bring it up in the future.
2.) Just kidding.
3.) There are also challenges to being stuck in the middle.
4.) Not least the numerous NMR jokes. Here's one I'm sure you've heard - “How many NMR spectroscopists does it take to prepare a sample?” “Zero – they get it from a collaborator.” For those of you who are only familiar with solution state NMR, the tradition of coming up with inventive names for pulse sequences also exists in solid state NMR – HORROR, MELODRAMA, CRAMPS, and WISE, among others.
5.) This comment is based on a postdoc candidate talk I gave at an MRI lab - one of the students remarked that he hadn't thought much about chemical shifts once he finished up his magnetic resonance class, as his dissertation research primarily focused on relaxation phenomenona.
Disclaimer - Any arguable/unrigorous point in the above post is 99.9% me being lazy about it.
4 hours ago
7 comments:
The biggest advantage is that I can lament the biological understanding of chemists and physicists, the physics blindness that chemists and biologists exhibit, and the appalling lack of chemical intuition that biologists and physicists demonstrate.
Indeed. The second biggest advantage is that you understand enough of what they are doing to talk them out of useful cultures/reagents/apparatus. And you can tune your speech to talk above them in one of the three areas, generally, so that you can make all but the super geniuses feel inadequate. Three Cheers for being cross disciplinary!
The corollary to that is that you can talk them into generously sharing cultures/reagents/apparatus with you so they can be associated with your groundbreaking and revolutionary ideas.
Well, that's what they think, at the very least. You're just happy you managed to get someone to agree to your latest harebrained idea. Heh.
Hey, I didn't think the latest Chemistry nobelists were unwashed pirate scum. They were definitely deserving...I just would have preferred to see them win one in medicine. :P
I think the issue is that given a choice between a biochemistry-oriented prize versus a clear-cut medicine (or even fundamental cell biology) prize, we're going to preferentially see the latter. Ones like last year's HIV-based prize, H. pylori prize in 2005, or the MRI prize in 2003 demonstrate that medical relevance still holds sway there.
For better or worse, the chemistry community still has to keep us biochemists/biophysical chemists in their ranks. You're not getting rid of us *that* quickly. ;)
o O (ALL YOUR NOBEL BELONG TO US.)
P.S. - Now, of course, since I said that, the 2009 chemistry Nobel will be so undeniably chemical in nature that no one - synthetic, analytical, materials, biological, medicinal - will be able to contest its worthiness.
For better or worse, the chemistry community still has to keep us biochemists/biophysical chemists in their ranks. You're not getting rid of us *that* quickly. ;)
Why? IME, biochemists are pretty useless! Since you're an NMR guy, though, you have valuable skills and may continue to live. ;)
Since you're an NMR guy, though, you have valuable skills and may continue to live. ;)
Give me your insoluble, your poorly ordered, your aggregated masses yearning to be analyzed....
Funny you should mention...I've made a lot of stuff that's at least two of those three. Oddly, solubility isn't often an issue...
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