Crystallization searches

Application of Phase Diagrams in Co-crystal Search and Preparation... 

Thermodynamic considerations offer a complementary approach for targeted co-crystal search and development. They can provide selection criteria for suitable co-crystal formers and can also help to predict the most promising preparation conditions. This includes the potential to reduce the experimental effort in co-crystal search and crystallization optimization significantly. Phase... 

Phase Diagrams for Most Efficient Co-crystal Search... 

In most instances it is not the purpose of a co-crystal search to find the maximum number of co-crystals, but to find at least one suitable co-crystal for further development. However, even if the discovery of a maximum number of co-crystals is intended, it will always be preferable to perform the search with... 

As this book makes it clear, the study of pharmaceutical co-crystals opens up new opportunities for the pharmaceutical industry. Several chapters of this book have addressed essential aspects, such as the role of co-crystals in the pharmaceutical development continuum (N. Schultheiss and J.-O. Henck), solid forms and pharmacokinetics (N. Biswas), the process of co-crystallization and scale up issues (E. Gagniere, D. Mangin, S. Veesler and F. Fuel), solid state analytical techniques and strategies for characterization (S. Reutzel-Edens) as well as opportunities and pitfalls when embarking on co-crystal search for broadening IP rights (M. Hoffmann and J. Lindeman). 

It may be desirable to predict which crystal structure is most stable in order to predict the products formed under thermodynamic conditions. This is a very difficult task. As of yet, no completely automated way to try all possible crystal structures formed from a particular collection of elements (analogous to a molecular conformation search) has been devised. Even if such an effort were attempted, the amount of computer power necessary would be enormous. Such studies usually test a collection of likely structures, which is by no means infal-... 

Currently, there are about 197,500 entries in the National Institute of Standards and Technology (NIST) Crystal Data File. An exhaustive search takes about one minute. Unit cell parameters are very definitive. Usually only one or a few hits are found and the appropriate Hterature reference(s) are Hsted. If no hits are found, the stmcture has not been previously reported. 

Indexings and Lattice Parameter Determination. From a powder pattern of a single component it is possible to determine the indices of many reflections. From this information and the 20-values for the reflections, it is possible to determine the unit cell parameters. As with single crystals this information can then be used to identify the material by searching the NIST Crystal Data File (see "SmaU Molecule Single Stmcture Determination" above). 

Diamonds were first discovered in ancient times in India and Borneo and later in Brazil in 1670 in alluvial deposits where water had sorted minerals on the basis of density and toughness. This type of tumbling often concentrates the better quality crystals such as those found in the ocean off the west coast of Africa. Exploration can be done by stream panning or drilling in conjunction with a search for the heavy mineral assemblages that accompany diamond. Alluvial deposits account for about 40% of the diamond found in primary sources. 

These difficulties have prompted a search for novel techniques for crystallization of membrane proteins. Two approaches have given promising results one using antibodies to solubilize the proteins and the second using continuous lipidic phases as crystallization media. Complexes with specific antibodies have larger polar surfaces than the membrane protein itself and are therefore likely to form crystals more easily in an aqueous enviroment. A recent example of an antibody-membrane protein complex utilized an Fv... 

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