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Chemists thrilled by speedy atomic structures (nature.com)
123 points by digital55 on Oct 29, 2018 | hide | past | favorite | 17 comments



Good commentary by a chemist here that should be understandable to non-chemists with some scientific background:

http://blogs.sciencemag.org/pipeline/archives/2018/10/18/sma...

It's interesting that both these new techniques and recent antecedents rely on a lot of computing power as well as new concepts and instruments. Cheap, powerful computing is the so-common-it's-invisible enabler for a lot of analytical techniques.


I’m not sure how cheap this computing is. I suppose maybe it is cheap in comparison to the electron microscope but I would guess that a large computer (but possibly not a supercomputer) would be needed to get some of these results. I guess that’s fine for universities though


According to the supplementary information in the Jones paper, they processed data using the XDS package.

https://strucbio.biologie.uni-konstanz.de/xdswiki/index.php/...

Here are some XDS benchmarks:

https://bl831.als.lbl.gov/~jamesh/benchmarks/

It looks like XDS will easily process a data set in well under an hour on any reasonably modern multicore CPU, and within a few minutes on a modern system with 16 or more cores. According to those numbers it looks perfectly usable on a laptop.


Oh wow, thanks for that. I was expecting it to need a lot more work than that.


These discoveries remind me very much of this "discovery" from a few years ago that promised equally astonishing shortcuts to solving chemical structures. I hope it turns out better though. Our lab was understandably never able to replicate the Japanese group's work and how simple they described the "crystalline sponge" method to be, no matter how hard we tried.

https://www.nature.com/articles/nature12527

We have plans to try these new methods also. Hope springs eternal...



This is truly astounding stuff. A huge chunk of analytical equipment for chemistry is concerned solely with determining the answers to two questions: what is a monomolecular substance made out of (e.g. elemental composition, chemical bonds, etc.) and what is the 3D atomic structure of this substance. That includes things like mass spectrometers, infrared spectrometers, raman spectrometers, NMR machines, and on and on. Some of these machines cost hundred of thousands or millions of dollars. Much of the rest of the analytical equipment is for separating mixtures of chemicals into separate monomolecular isolates.

These new techniques won't replace all of that equipment, but they will probably become just as common. X-ray crystallography is one of those things that is not as routine as all of the stuff above. Undergraduate chemistry students use GC-MS, and IR or NMR spectrometers, they do not generally do x-ray crystallography. Because it's a ton of work and the equipment is expensive. But if these techniques work as well as they seem to then we could be seeing a new addition to the list of analytical equipment in the vast majority of chemistry labs, and the addition of a new technique for routine chemical analysis.

And that's pretty astounding when you think about it because if you can take some sample that falls out of a chromatography column and then run it through the equipment listed above and this new process which provides atomic structures with small crystalline samples then you can learn basically all you need to know about a chemical within a few hours of "easy" work. That means Joe Blow amateur chemical lab can churn through tons and tons of samples and pump out structures of them like it was nothing. That means you can have a small footprint of lab equipment that you send to Mars or Ceres or the surface of a comet or what-have-you and you can investigate collected samples in situ to a degree that would have required returning them to Earth before.

It's very difficult to overstate just how transformative this innovation is going to be if it pans out at anything close to its apparent promise.


This has the potential to bring affordable chemical assays into reach of the average consumer.

The nootropics community will love this, making it easy to verify the composition of the bulk powders ordered from India or China.


It looks like the technique relies on the beam from a transmission electron microscope in the 200 kV range. These voltages, in turn, require very high vacuum compared to (e.g.) a more-common scanning electron microscope that's within reach of smaller labs and serious amateurs.

The sample must be maintained at cryogenic temperatures, presumably to make it stay put at the molecular level. Last but not least, they apparently need to rotate the sample stage to keep the sample from being blasted to pieces by the electron beam.

So unfortunately, the hardware isn't going to be easily packaged into something that consumers can afford.

If I had to come up with a drug-identification device, I would probably look into low-field NMR. You aren't trying to visualize the structure, right, just figure out what elements are present in what proportions?


If you want to match chemicals against a database, particularly organic ones, the easiest thing to build would be an IR spectrometer. You get a lot of random peaks in the sub-2000 cm¯¹ that is pretty damn unique, even for fairly close analogues. It's not going to be useful to determine a compound if it's not in the database, but that's usually not what you want in a identification device for consumer use.

> You aren't trying to visualize the structure, right, just figure out what elements are present in what proportions?

Elemental analysis is both rather easy (just burn it and measure out the CO₂/H₂O/NO₂/SO₂ + other impurities) and rather useless (a cyclohexane and a hexene both have the same chemical formula yet have very different structures and very different reactive potentials).

Inside chemical labs, NMR is the go-to method for identifying "is the compound in this jar what the label says it is?" But that's largely because every chemical lab has an NMR machine already, NMR makes all the functional groups pop out without much work, and if it's not in your database, you can still do a reasonable start on identification with just ¹H NMR. Considering the expense of NMR versus IR spectroscopy, database matching applications probably suffice with IR.


That’s not what this technique does. And for that, a commodity mass spec would work just fine right now.


go find some friendly drug chemists with GC/MSes. they can do what you want, cheaper, tomorrow.


A friend of mine showed me the chemRxiv paper and I realized that although I do research in protein biochemistry, it never occured to me that techniques other than NMR could be used for structural determination of organic molecules.

Its cool to take a look at some of the papers linked to realize that the structures are not at all what you would expect from intro level chemistry courses - an all sp2 hybridized molecule doesn't end up being perfectly planar in the crystal structure, it has a slight curvature to it (https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.2018113... paywall sorry), which is probably super important to know if you are trying to design protein inhibitors for therapeutic use.


Unless I misunderstand something, "a billion times 100 nanometers" would be 100 meter crystals (!) ?


Three dimensions. 1000 times larger in each dimension, so 100 micrometer crystals.


That would be it, good catch.


Wow, this is actually an incredible breakthrough, even though it's really only a breakthrough in information sharing between discplines.

But I look forward to using this technique for quickly identifying the structure of unknown organic molecules. Just gotta wait on the hardway now I guess.




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