
Chemists thrilled by speedy atomic structures - digital55
https://www.nature.com/articles/d41586-018-07213-3
======
philipkglass
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...](http://blogs.sciencemag.org/pipeline/archives/2018/10/18/small-
molecule-structures-a-new-world)

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.

~~~
dan-robertson
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

~~~
philipkglass
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/...](https://strucbio.biologie.uni-
konstanz.de/xdswiki/index.php/Main_Page)

Here are some XDS benchmarks:

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

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

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JohnJamesRambo
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](https://www.nature.com/articles/nature12527)

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

------
mhb
Small Molecular Structures: A New World - Derek Lowe

[http://blogs.sciencemag.org/pipeline/archives/2018/10/18/sma...](http://blogs.sciencemag.org/pipeline/archives/2018/10/18/small-
molecule-structures-a-new-world)

On HN:
[https://news.ycombinator.com/item?id=18273970](https://news.ycombinator.com/item?id=18273970)

------
InclinedPlane
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.

------
fouc
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.

~~~
CamperBob2
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?

~~~
jcranmer
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.

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dr_coffee
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...](https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201811318)
paywall sorry), which is probably super important to know if you are trying to
design protein inhibitors for therapeutic use.

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

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

~~~
hotpockets
That would be it, good catch.

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aldoushuxley001
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.

