X-ray diffraction methodologies

In a manner similar to that just described for differential thermal analysis, DSC can be used to obtain useful and characteristic thermal and melting point data for crystal polymorphs or solvate species. This information is of great importance to the pharmaceutical industry since many compounds can crystallize in more than one structural modification, and the FDA is vitally concerned with this possibility. Although the primary means of polymorph or solvate characterization s centered around x-ray diffraction methodology, in suitable situations thermal analysis can be used to advantage. 

The great majority of the applications of the x-ray diffraction methodology in material characterizations are carried out with the help of diffractometers, which use the Bragg-Brentano geometry. The principal characteristics of the Bragg-Brentano geometry are shown in Figure 1.24. 

The technique of x-ray diffraction is exceedingly important to pharmaceutics because it represents the primary method for obtaining fundamental structural information on crystalline substances. For example, it is only by pure coincidence that two compounds form crystals in which the three-dimensional spacing of planes is identical in all directions. One such example is provided by the trihydrate phases of ampicillin and amoxicillin, but such instances are uncommon. Typical applications of x-ray diffraction methodology include the determination of crystal structures, evaluation of polymorphism and solvate structures, evaluation of degrees of crystallinity, and the study of phase transitions. 

The crystal structures in Chapters 5 and 6 were determined by x-ray diffraction, and the papers illustrate Pauling s approach to this experimental technique, including his most notable methodological contributions—the coordination method (SP 42) and the stochastic method (SP 47). In its day, SP 47 was a tour de force in the determination of a complex crystal structure. SP 46 contains Pauling s famous discovery of two quite different crystal structures giving the same x-ray diffraction pattern, which violated the then-current conventional wisdom in x-ray crystallography. 

Typical applications of x-ray powder diffraction methodology include the evaluation of polymorphism and solvatomorphism, the study of phase transitions, and evaluation of degrees of crystallinity. More recently, advances have been made in the use of powder diffraction as a means to obtain solved crystal structures. A very useful complement to ordinary powder x-ray diffraction is variable temperature x-ray diffraction. In this method, the sample is contained on a stage that can be heated to any desired temperature. The method is extremely useful for the study of thermally induced phenomena, and can be a vital complement to thermal methods of analysis. 

Extending this methodology, Tamao and co-workers recently prepared a pentasilane, 4, containing a central trisilane unit constrained to the all-anti conformation by tethering with bis(tetramethylene) groups, as confirmed by single crystal X-ray diffraction.14... 

All these results are encouraging for investigators planning to use X-ray diffraction in mixed solvents at subzero temperatures and the rest of the present article will be devoted to a discussion of methods and preliminary results in this field. The methodology for cryoprotection of protein crystals, its physical-chemical basis, and the specific problems raised by the crystalline state, as well as the devices used to collect data at subzero temperatures, will be described. Limitations and perspectives of the procedure will be discussed critically. First attempts to determine the structure of productive enzyme-substrate intermediates through stop-action pictures will be described, as well as investigations showing that X-ray diffraction at selected normal and subzero temperatures can reveal protein structural dynamics. 

More recently, crown ether pillared and functionalized a-zirconium phosphonates have been synthesized [34], Incorporation of crown ethers was achieved by first converting them to their respective phosphonic acids. X-ray diffraction studies showed that the interlamellar spacing was about 15 A when a biphospho-nic acid was used. Both a- and y-type zirconium phosphonates could be synthesized using this methodology. Preliminary results showed that these layered materials have good selectivity toward binding transition metal ions and that the interlamellar fluoride ions could be replaced by anion exchange. 

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