Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases.
To contact Derek email him directly: derekb.lowe@gmail.com
Twitter: Dereklowe
Short Items: Viral NMR, Alarming Rings, Cheap Reading, Etc.
Posted by Derek
From PNAS, here’s an ingenious method that’s allowed NMR-based imaging of particles as small as viruses. I didn’t even think that this was possible – so now that it is, look for all kinds of variations on it over the next few years, as is the way of NMR techniques. Single-cell MRI? As the authors (from IBM) point out, this is a sudden 100-million-fold improvement in volume resolution compared to conventional NMR. It always makes me smile to see that things like this can happen.
This one should go into my “Things I Won’t Work With” folder immediately. Courtesy of Pat Dussault, whose lab has been turning out alarming stuff like this for some years now, we have six-membered rings made up of two carbons and four oxygens. There is no way to do that without putting on protective gear, needless to say – the only question is which stylish ensemble to wear.
And finally, I wanted to pass along this scientific reading suggestion to everyone. If you’re into magnetic resonance properties of silicon isotopes, you can read the book. After all, the list price is only $8539.00 (and don't forget, it's eligible for Free Super Saver Shipping!) But the rest of us can enjoy the Amazon reviews, which range from very satisfied customers (“My only question was whether one copy would be enough”) to very unsatisfied indeed. . .
Perhaps I'm missing a step here, but isn't it actually the advance in NMR noted by the virus structure paper, a revolution in how LARGE an object can be resolved at molecular level (as per your note that the next step would be NMR of a single cell 10^5-6 larger than a viral particle).
NMR is of course routinely used to determine structure of small molecules and more recently of small proteins. The major advance for drug discovery will NMR detection of structure for a large protein either in solution or (better yet) in the lipid bilayer - avoiding crytalization and X-ray diffraction.
So the major revolution must lie in managing the complexity of overlapping spectra that come from a large particle composed of a host of proteins.
2. Derek Lowe on January 16, 2009 10:24 AM writes...
Actually, when you do "regular" NMR of small molecules, you're getting averaged spectra of all the molecules in a given volume of the NMR tube, so the real spatial resolution isn't so great (and the number of molecules you're actually looking at is pretty large!)
Imaging applications need it, though, since in those cases you need to be able to distinguish one particular slice of the sample from another. There are a lot of technical problems - homogeneity of the magnetic field, signal-to-noise, and so on.
The "People who bought this also bought..." section is a little amusing - I guess they were figuring honing their lucid dreaming skills while acquiring NMR spectra would be a good way to pass the time, or maybe a good way to pay for the book.
It seems to be a multivolume series, so maybe the quoted price is for the series - it's almost a steal, then. 29 people have already bought it, which is at least 28 more than I would have expected.
Klapotke has a paper in JACS - it's not as exciting as the last one (silver azide can be manipulated on 2 mmol scale under their standard precautions, for example), but he is dependable for describing things you probably shouldn't (or at least shouldn't want to) do.
4. HelicalZz on January 16, 2009 11:45 AM writes...
"Chemical Shifts and Coupling Constants for Silicon-29"
Having read the book myself, I too was going to write a review ... but after looking over those already written, I couldn't think of anything germanium to add.
After reading the reviews of Gupta's book, (follow Derek's link to Amazon.com) I have decided that if the Hollywood writers go on strike again, all the producers have to do is employ the scientists, grad students, and other contributors to this blog. This gang is funnier than anybody in the Writers Union.
I am endlessly fascinated by MRFM, and it's always nice to see people pushing the state-of-the-art. (Although they're doing it in vacuum at 300 mK - so for those thinking that they'll get it to work in clinical trials next year, I wouldn't hold my breath.)
Re: the above comment -
The major advance for drug discovery will NMR detection of structure for a large protein either in solution or (better yet) in the lipid bilayer - avoiding crytalization and X-ray diffraction.
Not quite full structures just yet that I last remember seeing, but people are embedding membrane proteins into bilayers and various other assemblies and obtaining decent (solid state) NMR data. It's just a matter of time....
I have two copies of that book - one at home and one at work. You never know when you'll need to dig up something about Si-29 NMR, after all!
O Trinity of love and power!
Our scientists shield in layoff's hour;
From want and stress, and CEO,
Protect them whereso'er they go.
Thus evermore shall rise to Thee,
Glad praise from those who do chemistry!
Sales have obviously advanced since I last looked at the book, as it is not just lucid dreamers who bought the book (or maybe they are now having advanced lucid dreams). This week, someone who bought the book also bought several DVDs such as 'Naked Boys Singing'. Obviously a few University Libraries saw a couple of major gaps in their catalogues, hurriedly rectified.
I'm now rather curious as to why it goes for that sort of prices! (Or is this just someone's typo that's been compounded by people auto-copying from it?)
19. Tom Womack on January 20, 2009 5:19 AM writes...
The tetraoxanes look positively refined in comparison to most of the stuff you won't work with; the paper reports not a single explosion in the entire project, though has the normal warning about peroxides at the end.
20. Anonumoys on January 27, 2009 7:03 PM writes...
I don't see why there is a need for a $8500 book on NMR data. We first process the data on a supercomputer and then what do we do? Find the dead trees.
1. sak2011 on January 16, 2009 9:48 AM writes...
Perhaps I'm missing a step here, but isn't it actually the advance in NMR noted by the virus structure paper, a revolution in how LARGE an object can be resolved at molecular level (as per your note that the next step would be NMR of a single cell 10^5-6 larger than a viral particle).
NMR is of course routinely used to determine structure of small molecules and more recently of small proteins. The major advance for drug discovery will NMR detection of structure for a large protein either in solution or (better yet) in the lipid bilayer - avoiding crytalization and X-ray diffraction.
So the major revolution must lie in managing the complexity of overlapping spectra that come from a large particle composed of a host of proteins.
Is that right?
Permalink to Comment2. Derek Lowe on January 16, 2009 10:24 AM writes...
Actually, when you do "regular" NMR of small molecules, you're getting averaged spectra of all the molecules in a given volume of the NMR tube, so the real spatial resolution isn't so great (and the number of molecules you're actually looking at is pretty large!)
Imaging applications need it, though, since in those cases you need to be able to distinguish one particular slice of the sample from another. There are a lot of technical problems - homogeneity of the magnetic field, signal-to-noise, and so on.
Permalink to Comment3. Hap on January 16, 2009 11:17 AM writes...
The "People who bought this also bought..." section is a little amusing - I guess they were figuring honing their lucid dreaming skills while acquiring NMR spectra would be a good way to pass the time, or maybe a good way to pay for the book.
It seems to be a multivolume series, so maybe the quoted price is for the series - it's almost a steal, then. 29 people have already bought it, which is at least 28 more than I would have expected.
Klapotke has a paper in JACS - it's not as exciting as the last one (silver azide can be manipulated on 2 mmol scale under their standard precautions, for example), but he is dependable for describing things you probably shouldn't (or at least shouldn't want to) do.
Permalink to Comment4. HelicalZz on January 16, 2009 11:45 AM writes...
"Chemical Shifts and Coupling Constants for Silicon-29"
Having read the book myself, I too was going to write a review ... but after looking over those already written, I couldn't think of anything germanium to add.
Zz
Always up for a little group IVb humor.
Permalink to Comment5. Hap on January 16, 2009 2:40 PM writes...
I think there was a very bored set of graduate students at work on the Amazon reviews.
Permalink to Comment6. Bored on January 16, 2009 3:17 PM writes...
After reading the reviews of Gupta's book, (follow Derek's link to Amazon.com) I have decided that if the Hollywood writers go on strike again, all the producers have to do is employ the scientists, grad students, and other contributors to this blog. This gang is funnier than anybody in the Writers Union.
Permalink to Comment7. Wavefunction on January 16, 2009 3:55 PM writes...
Damn...it's silicon. I would have paid for it if it were titanium you know.
Permalink to Comment8. MJ on January 16, 2009 4:14 PM writes...
I am endlessly fascinated by MRFM, and it's always nice to see people pushing the state-of-the-art. (Although they're doing it in vacuum at 300 mK - so for those thinking that they'll get it to work in clinical trials next year, I wouldn't hold my breath.)
Re: the above comment -
The major advance for drug discovery will NMR detection of structure for a large protein either in solution or (better yet) in the lipid bilayer - avoiding crytalization and X-ray diffraction.
Not quite full structures just yet that I last remember seeing, but people are embedding membrane proteins into bilayers and various other assemblies and obtaining decent (solid state) NMR data. It's just a matter of time....
I have two copies of that book - one at home and one at work. You never know when you'll need to dig up something about Si-29 NMR, after all!
Permalink to Comment9. Jack Bauer on January 16, 2009 6:15 PM writes...
Call me naive, but that's one expensive book!
Permalink to Comment10. befuddled on January 16, 2009 8:33 PM writes...
A bargain indeed. At that price, the volume by Gupta et al is less than half the price by weight of gold!
Permalink to Comment11. Chemjobber on January 16, 2009 9:26 PM writes...
Maybe what Pfizer chemists need is a hymn:
O Trinity of love and power!
Permalink to CommentOur scientists shield in layoff's hour;
From want and stress, and CEO,
Protect them whereso'er they go.
Thus evermore shall rise to Thee,
Glad praise from those who do chemistry!
12. drug_hunter on January 16, 2009 9:35 PM writes...
Chemjobber, excellent parody, and much better lyrics than the old Navy hymn.
Permalink to Comment13. Chemjobber on January 16, 2009 9:38 PM writes...
Thanks, d_h. Like an idiot, I put it in the wrong thread. Score one against browser tabs.
Permalink to Comment14. Anonymous BMS Researcher on January 16, 2009 10:51 PM writes...
I like Chemjobber's wonderful parody. For many actual variants and new verses of the hymn, the Wikipedia article is fascinating:
http://en.wikipedia.org/wiki/Eternal_Father,_Strong_to_Save
Permalink to Comment15. Chemjobber on January 16, 2009 11:21 PM writes...
Thanks, ABR. I should add that I had written an additional verse. It is in the original post:
http://chemjobber.blogspot.com/2009/01/chemists-hymn.html
Permalink to Comment16. Andy on January 19, 2009 10:04 AM writes...
Sales have obviously advanced since I last looked at the book, as it is not just lucid dreamers who bought the book (or maybe they are now having advanced lucid dreams). This week, someone who bought the book also bought several DVDs such as 'Naked Boys Singing'. Obviously a few University Libraries saw a couple of major gaps in their catalogues, hurriedly rectified.
Permalink to Comment17. Anonymous on January 19, 2009 12:43 PM writes...
I like the guy who complained that he bought the book because he was caulking his shower, but still gave it 4-stars.
Permalink to Comment18. Brooks Moses on January 19, 2009 8:55 PM writes...
Well, if you don't like Amazon's price, you can find it listed for four times as much: http://www.papamedia.com/item.php?code=9783540452775.
I'm now rather curious as to why it goes for that sort of prices! (Or is this just someone's typo that's been compounded by people auto-copying from it?)
Permalink to Comment19. Tom Womack on January 20, 2009 5:19 AM writes...
The tetraoxanes look positively refined in comparison to most of the stuff you won't work with; the paper reports not a single explosion in the entire project, though has the normal warning about peroxides at the end.
Permalink to Comment20. Anonumoys on January 27, 2009 7:03 PM writes...
I don't see why there is a need for a $8500 book on NMR data. We first process the data on a supercomputer and then what do we do? Find the dead trees.
Permalink to Comment21. john on August 3, 2009 10:54 AM writes...
Well i have one for sale if naybody if intersted books is brand new, $ 6,999 is listed in Amazon.com
Permalink to Comment22. john on August 3, 2009 10:55 AM writes...
Well i have one for sale if naybody if intersted books is brand new, $ 6,999 is listed in Amazon.com
Permalink to Comment