Crystallization protocols

Hilfiker et al. at Solvias used carbamazepine (CBZ) as a model compound to describe the use of Raman microscopy to characterize crystal forms, including during solvent evaporation experiments [228], The spectra were processed into clusters by spectral similarity. The authors note that all published and several new crystal forms were identified during the study. Solvias HTS uses a specific set of crystallization protocols that have tended to produce new polymorphs. Hilfiker notes that Raman microspectroscopy is an ideal analytical tool for high-throughput discrimination between crystal structures. [229], The ability to collect spectra directly and automatically in a microtiter plate with or without solvent and during evaporation is a major advantage over many other techniques. 

Dilution experiments involve revisiting the crystallization drops which may cause disruption to the trial. An alternative way of backing off without touching the trial drop can be achieved in hanging drops in the following way the coverslips holding the drops are incubated for some time over reservoir solutions that normally give many small crystals (Protocol 3.6). 

To date robotic automation has been the dominant strategy both for miniaturizing standard crystallization protocols and for fostering high-throughput crystallization [11, 12]. This allows more trials to be conducted with a given sample volume. 

The orientation of crystalline stems with respect to the interface of the microstructure in block copolymers depends on both morphology and the speed of chain diffusion, which is controlled by block copolymer molecular weight and the crystallization protocol (i.e. cooling rate). In contrast to homopolymers, where folding of chains occurs such that stems are always perpendicular to the lamellar interface, a parallel orientation was observed for block copolymers crystallized from a lamellar melt phase perpendicular folding was observed in a cylindrical microstructure. Both orientations are shown in Fig. 8. Chain orientation can be probed via combined SAXS and WAXS on specimens oriented by shear or compression. In PE, for example, the orientation of (110) and (200) WAXS reflections with respect to Bragg peaks from the microstructure in the SAXS pattern enables the unit cell orientation to be deduced. Since PE stems are known to be oriented along the c axis, the chain orientation with respect to the microstructure can be determined. 

When crystallization conditions are already known, 1 mg of protein may be enough to produce a series of crystals with different inhibitors. One should bear in mind, however, that published crystallization protocols are often difficult to reproduce It is wise, in a first step, to follow as closely as possible the published expression, purification, and crystallization protocols. Particular attention should be paid to the protein construct, since minor changes to the amino acid sequence can have a dramatic influence on the solubility, stability, and crystallization behavior. 

The repeat unit of the PET molecule, the product of a condensation reaetion of terephthalic acid and ethylene glycol, was shown in Fig. 2.3 and is repeated here in Fig. 5.20. For their study, Illers and Breuer chose a commercial product with no detectable initial crystallinity, and removed all traces of residual stress as well as any previously existing water by appropriate prolonged thermal treatments above the glass-transition temperature of 67 °C. Different levels of crystallinity in samples were then obtained by nine separate isothermal crystallization protocols at temperatures ranging from 70 to 245 °C for pre-selected times until equilibrium crystallinities ranging from 0 to 46% were achieved in each case. Only samples subjected to temperatures above 86 °C showed X-ray evidence of crystallinity. 

The preparation of Wieland-Miescher ketone has sparked additional interest since the Hajos-Wiechert reaction provides it in lesser purity than the corresponding hydrindane derivative. The groups of Furst and Harada have reported two crystallization protocols for Wieland-Miescher ketone based on recrystallization fi om ether or a 10 1 ether/ethyl acetate blend these protocols, although time consuming, appear to be scaleable. ... 

Fabrication Standard 3D crystallization protocols (i) Many enzymes are polymorphic— prospect of tailoring CLEC morphology to application (ii) crystallization with activators/ cofactors possible for lipases, oxidoreductases, etc. Little is cmrently known about the influence of crystal macro-/ microstructure on CLEC activity and stability. 373, 377, 379, 381... 

---