Polymorphism importance

Pitarque M, von Richter O, Rodriguez-Antona C, Wang J, Oscarson M, Ingelman-Sundberg M. A nicotine C-oxidase gene (CYP2A6) polymorphism important for promoter activity. Hum Mutat 2004 23(3) 258-266. 

Many molecules are obtained and used in a crystalline form, the nature of which can have e significant impact on their properties and behaviour. Moreover, it is sometimes possible foi a given material to exist in more than one crystalline form, depending upon the conditions under which it was prepared. This is the phenomenon of polymorphism. This can be important because the various polymorphs may themselves have different properties. It is Iberefore of interest to be able to predict the three-dimensional atomic structure(s) that a gi en molecule may adopt, for those cases where it is difficult to obtain experimental data and also where one might wish to prioritise molecules not yet synthesised. 

Many different approaches have been suggested as possible approaches to this problem, from the 1960s onwards [Verwer and Leusen 1998]. What is obvious from all of these ellorts is that this is an extremely difficult problem. Both thermodynamics and kinetics can be important in determining which crystalline form is obtained under a certain se1 of experimental conditions. Kinetic effects are particularly difficult to take into accouni and so are usually ignored. A proper treatment of the thermodynamic factors would lequire one to deal with the relative free energies of the different possible polymorphs... 

A significant advantage of the PLM is in the differentiation and recognition of various forms of the same chemical substance polymorphic forms, eg, brookite, mtile, and anatase, three forms of titanium dioxide calcite, aragonite and vaterite, all forms of calcium carbonate Eorms I, II, III, and IV of HMX (a high explosive), etc. This is an important appHcation because most elements and compounds possess different crystal forms with very different physical properties. PLM is the only instmment mandated by the U.S. Environmental Protection Agency (EPA) for the detection and identification of the six forms of asbestos (qv) and other fibers in bulk samples. 

Another important pigment in this class is Pigment Red 170 [6985-95-17, which provides medium shades of red, and when particle-grown produces an opaque modification which shows improved migration resistance and lightfastness. Like some other Naphthol AS pigments it shows the phenomenon of polymorphism. 

Oxides. Owing to the importance as nuclear fuel material, actinide oxides have been intensively investigated. These are very compHcated compounds because of the formation of non stoichiometric or polymorphic materials. Actinide oxides are very heat-resistant and Th02 is the highest... 

Titanium Trichloride. Titanium trichloride [7705-07-9] exists in four different soHd polymorphs that have been much studied because of the importance of TiCl as a catalyst for the stereospecific polymerization of olefins (120,124). The a-, y-, and 5-forms are all violet and have close-packed layers of chlorines. The titaniums occupy the octahedral interstices between the layers. The three forms differ in the arrangement of the titaniums among the available octahedral sites. In a-TiCl, the chlorine sheets are hexagonaHy close-packed in y-TiCl, they are cubic close-packed. The brown P-form does not have a layer stmcture but, instead, consists of linear strands of titaniums, where each titanium is coordinated by three chlorines that act as a bridge to the next Ti The stmctural parameters are as follows ... 

Titanium Dioxide. The recrystallization of titanium dioxide in a cover-coat glass is very important to the development of thin, highly opaque finish coats. Titania, Ti02, is the primary opacifying agent for white finish coats. Two polymorphic forms of titania, anatase and mtile, may be present in... 

Fig. 2.1. Some metals hove more than one crystal structure. The most important examples of this polymorphism ore in iron and titanium.

The polymorphism of certain metals, iron the most important, was after centuries of study perceived to be the key to the hardening of steel. In the process of studying iron polymorphism, several decades were devoted to a red herring, as it proved this was the P-iron controversy. P-iron was for a long time regarded as a phase distinct from at-iron (Smith 1965) but eventually found to be merely the ferromagnetic form of ot-iron thus the supposed transition from P to a-iron was simply the Curie temperature, p-iron has disappeared from the iron-carbon phase diagram and all transformations are between a and y. 

In concluding this discussion, it is important to point out that crystalline polymers can be polymorphic because of slight differences in the conformation of the helical disposition of stereoregular polymer chains the polymorphism is attributable to differences in the weak intermolecular bonds. This abstruse phenomenon (which does not have the same centrality in polymer science as it does in inorganic materials science) is treated by Lotz and Wittmann (1993). 

Oxides of the actinides are refractory materials and, in fact, Th02 has the highest mp (3390°C) of any oxide. They have been extensively studied because of their importance as nuclear fuels. However, they are exceedingly complicated because of the prevalence of polymorphism, nonstoichiometry and intermediate phases. The simple stoichiometries quoted in Table 31.5 should therefore be regarded as idealized compositions. 

Process validation should be extended to those steps determined to be critical to the quality and purity of the enantiopure drug. Establishing impurity profiles is an important aspect of process validation. One should consider chemical purity, enantiomeric excess by quantitative assays for impurity profiles, physical characteristics such as particle size, polymorphic forms, moisture and solvent content, and homogeneity. In principle, the SMB process validation should provide conclusive evidence that the levels of contaminants (chemical impurities, enantioenrichment of unwanted enantiomer) is reduced as processing proceeds during the purification process. 

Buscher, R., Hermann, V., and Insel, P. A. (1999). Human adrenoceptor polymorphisms Evolving recognition of clinical importance. Trends Pharmacol. Sci. 20 94-99. 

The CP/MAS NMR spectra are an important source of information regarding the structure of cellulose and its polymorphos. A number of groups have investigated these spectra 11 15) and also reviews on the subject have been published 16 17>. For an orientation in the field Table 1 shows the most important features of the solid-state NMR spectra of cellulose I, II and IV and in Fig. 3 the numeration of the carbon atoms of the cellulose basic unit is given. It is evident that the polymorphs... 

Many of the investigated mesogenic compounds show solid state polymorphism. In order to obtain useful information about the arrangement of the molecules in the mesophase from the X-ray data of the single crystals, it is important to investigate the crystal structure of those solid phase which transforms into the liquid crystalline phase. For instance, only the crystal structures of the low temperature solid phases of the compounds MBBA [138, 139], MHPOBC [159], and T15 [81] could be determined, but the... 

Table 53-2. Some important drug reactions due to mutant or polymorphic forms of enzymes or...

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

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