Fantastical Fridays: NMR Goes Natural, Baby!

Blogging on Peer-Reviewed ResearchThere are a number of approaches scientists take to get at the fundamental nature of life, and one of those is elucidating the chemical structures of the molecules that make life happen, particularly proteins, which are the workhorses of the cell. One of the two primary methods for determining these structures is nuclear magnetic resonance (NMR) and the other is x-ray crystallography. My current work is in the former, meaning I spend a lot of time sitting in front of a huge magnet and even more time staring at a computer screen trying to make sense of the data I get from the magnet. As people in the field continue to try to build bigger and bigger magnets to acquire better NMR data, though, one group reported earlier this year in Nature Physics that sometimes it may be better to just go natural. Forget about all of the high-tech magnets--just use the big one right under your feet!

One's small, but fierce. The other has bulk, but lacks strength. Let the battle begin!


Note: the fundamentals of NMR are a subject for another post, but, in short, here's how it works. Each protein is made up of thousands of atoms organized in a specific three-dimensional conformation, and each of those atoms has a nucleus with a magnetic moment. Normally, the magnetic moments of these nuclei are arranged randomly, but within a strong magnetic field they all line up. When a nucleus absorbs radio waves, though, its magnetic moment will spin around in a circle, in turn emitting its own radio waves, which can be detected. A given type of atom (hydrogen, nitrogen, carbon, etc.) will emit radio waves at a characteristic frequency. However, this frequency will vary slightly depending on the chemical environment that a particular atom is in. Scientists can use this difference, called a "chemical shift", to obtain valuable structural information about a protein (or any other type of molecule). The stronger the magnet is, the larger the observed chemical shifts, so bigger and better magnets are constantly being developed.

In NMR, bigger really is better, at least when it comes to magnetic field strength, and the entire field has in some ways become one big manhood size-measuring contest. (A contest, I should add, that the lab I'm in is currently winning, with our new 22.3 Tesla (950 MHz) magnet, which is the most powerful NMR magnet in the world.... OK, I'll admit that it kind of sounds like there might be some deep-seated issues at play here....) These high field magnets, though, are incredibly complex and expensive, relying on advanced superconductor technology to stably generate such a strong magnetic field.

In the February 2006 issue of Nature Physics, a team led by Stephan Appelt of Jülich research center demonstrated that sometimes may have provided us with the best NMR machine of all, the Earth. While the Earth is literally a much bigger than any magnet humans have ever built, it's several orders of magnitude weaker than the magnets routinely used in NMR. For example, our new 22.3 Tesla machine generates a field roughly 500,000 times stronger than the magnetic field of the Earth. The group from Jülich, though, showed that for certain application, the Earth's magnetic field actually yields better results.

So, how did they manage to get better results from a much weaker magnetic field? There are two reasons. Firstly, although the Earth's magnetic field is weak, it is remarkably homogeneous compared to the field generated by an NMR magnet. As anyone who has worked with NMR will surely attest to, one of the most frustrating and time-consuming parts of setting up any NMR experiment is a process called shimming, which involves tediously adjusting several smaller magnets around the main magnet to correct for inconsistencies in the magnetic field. The reason for all of this effort is that a more homogeneous field yields better results.

The second reason for the utility of the Earth's magnetic field in NMR stems from the fact that the environment outside of an NMR machine, particularly the presence of metal objects, can influence the results of an experiment. Although a normal NMR machine is stationary, since this particular study didn't need a superconducting magnet, these scientists were able to build a portable NMR machine that they could use to perform their experiments far from the complications that arise from civilization and its metallic infrastructure. In this case, they were studying J-coupling, one of the many phenomena observable by NMR. Since J-couplings are particularly sensitive to these outside influences, the authors obtained better results from the Earth's magnetic field than from superconducting magnets.

So, do we need to demand to get our money back for our new huge and expensive magnet? Not at all. The scientists at Jülich were studying J-couplings, which are not dependent on the field strength. In contrast, protein NMR, the work we do in our lab, is very dependent on measuring chemical shifts, which do depend on field strength. For example, let's say we're looking at the peaks from two hydrogen atoms in an NMR spectrum acquired on the 22.3 Tesla machine, and they're separated by 450 Hz. In this spectrum, we will easily see these two peaks as distinct and separate. If we were looking at the same spectrum obtained from the Earth's magnetic field (about 0.00005 Tesla), these two peaks would only be separated by 0.001 Hz, making them virtually indistinguishable. So, the findings of this study won't be transforming protein NMR anytime soon.

Still, after spending long hours hiding away in the basement of our building with only the very expensive company of a few NMR machines, I find the idea of performing NMR experiments and being able to reconnect with nature at the same time undeniably appealing.

Stephan Appelt, Holger Kuhn, F. Wolfgang Hasing and Bernhard Blumich, Chemical analysis by ultrahigh-resolution nuclear magnetic resonance in the Earth's magnetic field, Nature Physics 2 (2006), 105-9.


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Of course, spin isn't really spin in the classical sense of a rotating top, but the contribution to the angular momentum of a quantum object. Which in the same vein means that the magnetic moment can't be lined up precisely to an external magnetic field. And NMR experiments don't just measure what the new frequencies are, but also how long the atomic nuclei stay oriented. But you knew that, of course.

When it comes down to it, "spin" is just a label, just like most other quantum mechanical terms. Regardless, NMR is too complicated to confuse people with all of the complexities of the method (I know, I'm still figuring it all out). ;-)

The Science Fiction novel I never wrote but thought about on many a night in grad school involves a journey to a neutron star with a bunch of samples in Wilmad 5 mm tubes......

By thomas Barta (not verified) on 05 Jul 2006 #permalink

Since I've chanced (via "Nature" via Pharyngula) on a magnet expert, I have a question I'm too lazy to figure out the answer to myself. A guy I know has this theory--Noah's Flood was caused by a huge space snowball that impacted Earth's magnetic field and broke up and/or was diverted to the poles to become rain and/or polar icecaps.

Dumb theory, sez I. First, ice doesn't "impact" with magnetic fields--try to pick up ice with a magnet. "Oh ho!" sez he. "The ice is so cold it's magnetic. You get to -276 K, you're magnetic."

Second, sez I, the magnetic field is too weak. It can barely pull an itty bitty compass needle to North--it can't deflect humongous snowballs. "Oh ho!" sez he. "The magnetic field was stronger back in the day."

I know his theory is crackpot, but I don't know 1) if supercold ice is magnetic or 2) how many natural laws would have to be violated for the magnetic field to be strong enough to have set the Flood in motion.

It sounds like you're right. Water is not magnetic. For an element or molecule to be magnetic in the classical sense, it must have unpaired electrons. All of water's electrons are paired. The nuclear magnetic effect is incredibly weak and unlikely to have any observable effects on such a scale. I don't know the history of Earth's magnetic field, but it is very weak and even if it used to be stronger, it is unlikely that it would have to be so many orders of magnitude stronger to influence the trajectory of outerspace objects that this sounds pretty impossible (particularly in relation to the force of gravity). Stars, particularly neutron stars, can have incredibly strong magnetic fields, but all in all, this idea sounds pretty crazy.

Hmmm...go to a faucet and turn the water on till it is a thin stream. Take a full balloon and rub it againt your hair. Place it near the stream. Discuss.

I was pretty sure I'd covered this last year for the NMR channel on and sure enough I had -…

"German researchers have demonstrated that the earth's magnetic field is perfectly adequate for carrying out NMR studies. Their discovery could lead to a highly sensitive way to measure the magnetic fields around living creatures, sample the Earth's magnetic field, or test the composition of mineral oils in wells..."

It is the same team but they published their preliminary results in Phys Rev Lett 2005, 94, 197602

That's interesting. I hadn't seen that paper. It looks like the Nature Physics paper is significant, though, because it is there that the authors really demonstrate the utility of using the Earth's magnetic field for measuring J-couplings.

completely agree with you that the concept of getting rid of a technological invention is troublesome. Technology usually isn't the problem, it's how it's used-- but I have another problem beyond that. If we say "I wish nobody had invented the atomic bomb," great. But that just means somebody will later. If it can be done, and if it can be done practially, given enough time eventually it will be. The trick is learning how to live with the consequences of having that technology, not just making it go away.

But there are lots of social inventions that are terrible things. And, software patents and business method patents are two of those things that arose in the last hundred years (as extensions of more traditional patents) that I wish we'd never come up with.

As an astronomer, another one is "landscape lighting." Terrible waste of energy, terrible to just throw photons upwards where nobody needs them and it blots out our view of the sky.

NMR goes critical for drug separations
It is taken as read that the pharmaceutical industry has to perform countless separations during R&D before the safest, purest, or most effective compound can be incorporated into a new product. However, mainstream industry has yet to take full advantage of one of the cleanest approaches to separations - using supercritical fluids.