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When I was an organic chemist, growing crystals was of paramount importance for certain structure determinations using X-ray crystallography (to answer "did I r

When I was an organic chemist, growing crystals was of paramount importance for certain structure determinations using X-ray crystallography (to answer "did I really prepare what I think I prepared?") With sensitive compounds, sometimes you can't just let things evaporate. Also as the article states, weather conditions might mess you up. IMO the coolest trick we had to solve this was osmosis of an anti-solvent into a saturated solution. A small sealed container with a saturated solution of your compound/salt is punctured, and put in a bigger sealed container containing a worse but miscible solvent for the compound under study. Slow diffusion into the inner container causes very reproducible crystal growth, as long as you can control the temperature.

andrewla 5y ago
Neat -- turns out that for sodium chloride there is extensive literature on this. Ethanol is apparently effective as an anti-solvent, but various dimethylisopropylamine compounds appear to be more effective and are used in industrial settings. Interested now to try this experiment but with ethanol to better control the crystal formation.
- isoprophlex 5y ago
  Wonderful! I was tempted to do some searching on ethanol, acetone, any volatile things that are generally available... good to know ethanol is effective. Will be a fun xmas experiment to do!
voldacar 5y ago
That's really clever. How long did this process usually take, what size crystals were you going for? And were these crystals ever visually interesting, or do most organic compounds just form colorless little prisms or cubes?
- isoprophlex 5y ago
  "Sadly" (not for me back then) a crystal 1 mm on a side is more than plenty for structural elucidation. They were only ever pretty to me because A) you sometimes spend weeks working on the materials that go into the solution, seeing them feels like a "my god finally" kinda thing B) under a microscope crystals are especially beautiful, even small crystals. We had a microscope set up in an inert atmosphere for sensitive compounds, see eg. https://www.jacomex.com/wp-content/uploads/2019/08/microscope-glove-box-2.jpg https://www.jacomex.com/wp-content/uploads/2019/08/microscop... About timing: this could take anywhere from days to months... really dependent on how fast you can go without making ugly intergrown xtals, on how well you select solvents, etc. Experimental science can be cruel.
gwerbret 5y ago
> growing crystals was of paramount importance for certain structure determinations using X-ray crystallography (to answer "did I really prepare what I think I prepared?") Ahh, X-ray crystallography, a.k.a. the field of modern (bio)chemistry that most closely resembles medieval alchemy. The excellent 2009 documentary "Naturally Obsessed" [0] is about how difficult, time-consuming, and frankly irrational it can be to successfully crystallize certain proteins and protein complexes. The film is about how some PhD students spend the entire five-ish years of their degree programs trying (and mostly failing) to find the secret recipes (protein purity/additive ingredients/temperature/humidity/phase of the moon) that will allow their proteins to crystallize, and thus granting them data with which to populate their dissertations. Why irrational? In one case, the secret ingredient is pickle juice. [0]: https://www.thirteen.org/naturally-obsessed/ https://www.thirteen.org/naturally-obsessed/
- divbzero 5y ago
  > Ahh, X-ray crystallography, a.k.a. the field of modern (bio)chemistry that most closely resembles medieval alchemy. This is amusingly accurate and makes me wonder if our understanding and techniques will ever advance to the point where crystallography no longer feels like medieval alchemy. Surely the process is largely deterministic and we simply can’t control the relevant initial conditions with our current methods.
  - mahkeiro 5y ago
    Fortunately cryo-EM is helping to overcome the cristallography bottleneck. B progress regarding cryo-EM resolution have been made in the last years.
    - hoseja 5y ago
      Has it's own share of alchemy. Remember, the water has to remain vitreous. This is sometimes quite incompatible with the environment proteins want to exist in in their natural state.

andrewla 5y ago

Neat -- turns out that for sodium chloride there is extensive literature on this. Ethanol is apparently effective as an anti-solvent, but various dimethylisopropylamine compounds appear to be more effective and are used in industrial settings. Interested now to try this experiment but with ethanol to better control the crystal formation.

isoprophlex 5y ago
Wonderful! I was tempted to do some searching on ethanol, acetone, any volatile things that are generally available... good to know ethanol is effective. Will be a fun xmas experiment to do!

voldacar 5y ago

That's really clever. How long did this process usually take, what size crystals were you going for? And were these crystals ever visually interesting, or do most organic compounds just form colorless little prisms or cubes?

isoprophlex 5y ago
"Sadly" (not for me back then) a crystal 1 mm on a side is more than plenty for structural elucidation. They were only ever pretty to me because A) you sometimes spend weeks working on the materials that go into the solution, seeing them feels like a "my god finally" kinda thing B) under a microscope crystals are especially beautiful, even small crystals. We had a microscope set up in an inert atmosphere for sensitive compounds, see eg. https://www.jacomex.com/wp-content/uploads/2019/08/microscope-glove-box-2.jpg https://www.jacomex.com/wp-content/uploads/2019/08/microscop... About timing: this could take anywhere from days to months... really dependent on how fast you can go without making ugly intergrown xtals, on how well you select solvents, etc. Experimental science can be cruel.

gwerbret 5y ago

> growing crystals was of paramount importance for certain structure determinations using X-ray crystallography (to answer "did I really prepare what I think I prepared?") Ahh, X-ray crystallography, a.k.a. the field of modern (bio)chemistry that most closely resembles medieval alchemy. The excellent 2009 documentary "Naturally Obsessed" [0] is about how difficult, time-consuming, and frankly irrational it can be to successfully crystallize certain proteins and protein complexes. The film is about how some PhD students spend the entire five-ish years of their degree programs trying (and mostly failing) to find the secret recipes (protein purity/additive ingredients/temperature/humidity/phase of the moon) that will allow their proteins to crystallize, and thus granting them data with which to populate their dissertations. Why irrational? In one case, the secret ingredient is pickle juice. [0]: https://www.thirteen.org/naturally-obsessed/ https://www.thirteen.org/naturally-obsessed/

divbzero 5y ago
> Ahh, X-ray crystallography, a.k.a. the field of modern (bio)chemistry that most closely resembles medieval alchemy. This is amusingly accurate and makes me wonder if our understanding and techniques will ever advance to the point where crystallography no longer feels like medieval alchemy. Surely the process is largely deterministic and we simply can’t control the relevant initial conditions with our current methods.
- mahkeiro 5y ago
  Fortunately cryo-EM is helping to overcome the cristallography bottleneck. B progress regarding cryo-EM resolution have been made in the last years.
  - hoseja 5y ago
    Has it's own share of alchemy. Remember, the water has to remain vitreous. This is sometimes quite incompatible with the environment proteins want to exist in in their natural state.