International
Tables for
Crystallography
Volume C
Mathematical, physical and chemical tables
Edited by E. Prince

International Tables for Crystallography (2006). Vol. C, ch. 3.1, p. 149

Table 3.1.1.1 

P. F. Lindleya

aESRF, Avenue des Martyrs, BP 220, F-38043 Grenoble CEDEX, France

Table 3.1.1.1| top | pdf |
Survey of crystallization techniques suitable for the crystallization of low-molecular-weight organic compounds for X-ray crystallography (adapted from van der Sluis, Hezemans & Kroon, 1989[link])

TechniqueAdvantage(s)Limitation(s)
Evaporation from a single solvent Simple
Inexpensive
Limitation to solvents with adequate vapour pressure
Crust formation on tube walls
Crystals that are dried are less suitable as seeds, may lose included solvent and become tightly adhered to the crystallization vessel
Difficult to reproduce
Limited number of solvents give concentration 5–200 mg ml−1 for a particular compound
Evaporation from a binary mixture of solvents (volatile solvent and non-volatile precipitant) No crust formation on the tube walls
Crystals are not dried
Stringent demands on solubility, miscibility and volatility of the two solvents
Difficult to reproduce
Batch crystallization No demands on the volatility of the solvent or precipitant
Repeated seeding by thermal treatment is easy
Metastable zone with regard to supersaturation must be large
High and almost uncontrollable crystallization rate
Solvents must be miscible
Liquid–liquid diffusion Favourable change in supersaturation at the interface during crystallization
Repeated seeding by thermal treatment is easy
Density differences required for the two liquids (less stringent if capillaries are used)
Viscosity of the liquids greater than water
Solvents must be miscible
High and almost uncontrollable crystallization rate
Sitting-drop vapour-phase diffusion Crystallization rate can easily be controlled by changing the diffusion path, solvent, precipitant, or pH
Repeated seeding easily implemented
Highest number of independent variables to obtain wide variety of conditions
Solvents must be miscible
Solvent preferably less volatile than precipitant
Hanging-drop vapour-phase diffusion Crystallization rate can easily be controlled by changing solvent, precipitant, or pH
Easy examination of crystallization outcome in array-like set-up
Only applicable in case of water-based solvents
Diffusion rate is fast and difficult to control
See previous method
Temperature change Easily controllable parameter
Repeated seeding extremely easily and accurately carried out
With Dewar flask inexpensive and simple
Limited to thermally stable compounds and (pseudo)polymorphs
Gel crystallization Suited for sparingly soluble or easily nucleating compounds Limited variety of solvents possible
Sampling of crystals difficult
Laborious
Sublimation No inclusion of solvent of crystallization Limited to small hydrophobic molecules
Laborious
Solidification For liquids and gases the only applicable method Limited to thermostable compounds
High change of amorphicity
Laborious