Crystallization of low-molecular-weight organic compounds for X-ray crystallography

Abstract

General strategies are described to obtain crystals of low-molecular-weight compounds suitable for X-ray structure determination. A survey is given of a variety of crystallization techniques together with their advantages and drawbacks, illustrated by experiences with notoriously crystallization-resisting compounds. The methods discussed range from preliminary investigations using evaporation, batch crystallization and liquid-liquid diffusion methods, via the most frequently used methods such as sitting-drop vaporphase diffusion and change of temperature, to methods such as gel crystallization, sublimation and solidification. The most successful method appears to be the sitting-drop vapor-phase diffusion. Complete crystallization routes are described, taking into account the results of preliminary investigations. The hard-to-crystallize vecuronium bromide is presented as a case study.

An Augmented Volume-Based Model of the Glass Transition Temperature of 209 Molecular Liquids

“…For example, experimental lattice structures of 3‐toluidine and ( trans ‐)decalin were only published during the last decade 79–80. This could mean that it is hard to find conditions for them to either form crystals at all, or ones that are suitable for structural elucidation 81…”

“…[79][80] This could mean that it is hard to find conditions for them to either form crystals at all, or ones that are suitable for structural elucidation. 81 For our study, we excluded polymers. One reason, apart from the question how to computationally treat basically infinite molecular chains, is their nontrivial purification, resulting in mixtures with different chain lengths.…”

Chemistry and Crystal Growth

“…Initial attempts at designing a versatile set of apparatus for purposeful crystallization are already in existence,I1OO. 115,1161 Exploratory techniques have the advantage that they require relatively simple equipment in the chemical laboratory and that only small amounts of substance are necessary. The process operation has the best possible control of crystallization parameters, preferably self-regulating.…”

Chemical crystallography–science, technology or a black art

“…Some recommend using very pure solvents 'The solubility of the compound in a precipitant used in a two solvent crystallization method such as vapor diffusion should be as low as possible ($1 mg mL À1 ) and the precipitant should be miscible with the solvent and the saturated solution. The purity of the selected solvents and precipitants should be as high as possible to avoid contamination of the compound' (72). Others propose mixed solvents 'Under any circumstance, the use of solvent mixtures could prove useful.…”