How To Grow Crystals
Download a PDF version of this document HERE: How to Grow Crystals
Step 1: Considerations about the charge of your molecule. Small Scale Tests
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If you expect your molecule is negative you may need to add a cation to your solution. Potential cations include
- Tetrabutylammonium Halides (TBABr, TBACl, TBAI)
- Tetraethylammonium Halides (TEABr, TEACl, TEAI)
- Tetramethylammonium Halides (TMABr, TMACl, TMAI)
- Tetramethyphosphonium halides (TMPBr, TMPCl)
- Tetrabuytlphosphonium halides (TBPBr, TBPCl)
- Triphenylmethyl halide (TPMBr, TPMCl)
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If you expect your molecule is positive you many need to add an anion to your solution. Potential anions include:
- Ammonium hexafluorophosphate (NH4PF6)
- Ammonium borohydride (NH4BH4)
- Alkali Earth Metal /Amomonium nitrate (ANO3/NH4 NO3)
- Alkali Earth Metal /Ammonium Perchlorates (AClO4/NH4ClO4)
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If you expect your molecule is neutral and you believe you will have trouble getting crystals here are some molecules which can help yield better crystals.
- Triphenylphosphine
- Triphenylphosphine oxide (TTPO)
Step 2: Different methods of crystallization
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Undisturbed solution: leaving solution in a location where it will be undisturbed by vibrations or movement.
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Slow evaporation: allowing the concentration of you solution to slowly increase (leading to saturation) by solvent evaporation.
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Slow cooling: allowing your solution to cool from a higher temperature to room temperature over a long time period (anywhere from several hours to multiple days.)
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Vapor diffusion: allowing a solvent of high volatility to slowly diffuse into a sample of lower volatility. (Figures from: http://www.chemistryviews.org/details/education/2538941/Tips_and_Tricks_for_the_Lab_Growing_Crystals_Part_3.html)
Air Stable:
Air-Free:
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Layering (Solvent Diffusion): Uses the advantage of density for two different solvents. The solution (dc) is either layered under (if density of layering solvent is lighter dc > dl) or on top of (if density of layering solvent is higher dc < dl) the layering solvent (lc).
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Sublimation: heat the sample solution under reduced pressure until it vaporizes and allow it to undergo deposition on a cool area of the surface.
Step 3: Is your molecule soluble in polar or non-polar solvents?
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List of Polar Solvents
A. Aprotic Polar Solvents
-Acetonitrile (MeCN)
- Layer with ether, ether/hexane (1:1), acetone, acetone/hexane (1:1), dichloromethane (DCM aka methylene chloride), chloroform, toluene, THF
- Diffusion with ether, E/H, Me2CO, DCM
-Dimethylsulfoxide (DMSO)
- Layer with ether, acetone, ether/acetone
- Diffusion with E/H, Ether/Acetone, Acetone
-Dimethylformamide (DMF)
- Layer with ether, acetone, ether/acetone, hexane, ether/hexane
- Diffusion with E/H, Hexane, Ether/Acetone, Acetone
-Acetone (Me2CO)
B. Polar Protic Solvents
-Ethanol (EtOH)
- Layer with acetone, ether, ether/acetone, water, acetonitrile
- Diffuse with acetone, ether, ether/acetone
-Methanol (MeOH)
- Layer with acetone, ether, ether/acetone, water, acetonitrile
- Diffuse with acetone, ether, ether/acetone
-tertButanol (tBuOH)
- Layer with acetone, ether, ether/acetone, water, acetonitrile
- Diffuse with acetone, ether, ether/acetone
-Water (H2O)
- Layer with acetone, alcohols
- Diffuse with alcohol, methanol
-nPropanol (nPrOH)
- Layer with acetone, ether, ether/acetone, water, acetonitrile
- Diffuse with acetone, ether, ether/acetone
C. Borderline Aprotic Solvents
-Tetrahydrofuran (THF)
- Layer with alcohols, acetonitrile, DCM, nitromethane, chloroform
- Diffuse with alcohols, DCM
-Ethylacetate (Et2OAc)
-Dichloromethane (DCM)
- Layer with ether, ether/hexane, hexane, acetonitrile
D. Nonpolar Solvents
-Pentane (P)
- Layer with ether, acetone, ether/acetone, acetonitrile
- Diffusion with ether, acetone
-Hexane (H)
- Layer with ether, acetone, ether/acetone, acetonitrile
- Diffusion with ether, acetone
-Cyclohexane (CH)
- Layer with ether, acetone, ether/acetone, acetonitrile
- Diffusion with ether, acetone
-Benzene (Bz)
- Layer with ether, acetone, ether/acetone, acetonitrile
- Diffusion with ether, acetone
-Toluene (Tol)
- Layer with acetonitrile, hexanes, pentane, ether, DCM
- Diffusion with hexane, ether, DCM
-Chloroform (CHCl3)
- Layer with ether, hexane, ether/hexane, pentane, ether/pentane, acetonitrile
- Diffuse with ether, hexane
-Ethyl Ether (Et2O)
- Layer with acetone, acetonitrile, ethyl acetate, hexane
**If these solvents do not work you can also layer any solvent with another solvent it is miscible with (see chart below)
Step 4: What if crystals are not growing?
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Try adding one of the neutral molecules to act as a cocrystallizaer.
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Place reaction in fridge, sometimes a change in temperature (or cooler temperatures) can induct crystalliations.
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Use a seed crystal or slightly scratch the glass to create a nucleation site.
Step 5: I have crystals but they’re not suitable for data collection. What do I do?
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Recrystallization – dissolve your crystals in another solvent (test for solubility by using a small amount of crystals and scanning different solvents) and layer back with the solvent they originally crystallize from or one from the miscibility chart.
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Place vial in the fridge to slow the process of crystallization and hopefully yield better crystals.
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Decrease the concentration of your solution so the crystals have more room to form single crystals.
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Try using a similar solvent system (i.e. chloroform for DCM, nitromethane for acetonitrile, ethanol for methanol) or a mixture of solvents (pick two solvents which are miscible).