X-ray Quality Single Crystals within Six Hours

Growing single crystals with the CrystalBreeder by thermocycling

Would you like to know the crystal structure of your active ingredient? Do you see the need of having the molecular structure confirmed? Do you want to be able to understand physicochemical properties of your Active Ingredient? Growing X-ray quality crystals would help you to answer these questions. Why specifically quality crystals? Grow quality crystals to make sure you are not losing useful chemical information. X-ray quality crystals have to exhibits a high degree of internal order as evidence by the presence of an X-ray diffraction pattern and reaches in size between 0.1 - 0.4 mm in at least two of the three dimensions. The CrystalBreeder instrument brings to you the technology to grow quality single crystals without having to give special attention and extra time to your experiments.

The growth of single crystals was studied by thermal crystallization with the help of the CrystalBreeder on a series of very different compounds. The study was performed by Prof. Dr. Bernhard Spingler and his team at Zurich University on a few compounds including carbamazepine, p-aminobenzoic acid and vitamin B12.

For thermal recrystallization, it is essential to know the solubility in the chosen solvent at a selected temperature in order to obtain supersaturation at the cooling step. In general, a set of solvents are chosen for investigating the solubility of the compound of interest. Moreover, four different concentrations at room temperature (RT) were chosen for the crystallization experiments: 75%, 100%, 150%, and 200%. Each sample followed the temperature profile depicted here.

Colorless, thin needles and prismatic single crystals were obtained for carbamazepine. The crystal structure of the two forms was successfully determined by X-ray powder diffraction analysis. Suitable single crystals for X-ray diffraction analysis were also obtained from p-aminobenzoic acid.

One of the observations was that thermal recrystallization can be performed very fast. Single crystals suitable for X-ray diffraction analysis were obtained for carbamazepine and p-amino benzoic acid within six hours. More importantly, the quality of the obtained single crystal for these compounds was excellent. Furthermore, only small amounts of material (as little as 1.5 mg) were used.

 

 
Technobis Crystallization Systems is highly grateful to Prof. Dr. Bernhard Spingler and his team from Zurich University for the help with this case study.
Nievergelt, Philipp P; Spingler, Bernhard (2017). Growing single crystals of small molecules by thermal recrystallization, a viable option even for minute amounts of material; CrystEngComm, 19(1):142-147.