Polymorphism in organic crystals

A total of 163 clusters were obtained, where a cluster is a group of polymorphic crystal structures of the same compound. Of the 163 clusters, 147 contained two structures, 13 had three, and three had four structures. The authors note that these numbers are first evidence of the high frequency of polymorphism in organic crystals , although the number of clusters is a relatively small percentage of the entries in the database. The number of these clusters is probably more a measure of certain authors interest in the particular polymorphic system in question. A more realistic measure (although certainly not precise because of the caveats mentioned above) of the frequency of polymorphism in these compounds wouid be the fraction of compounds in the database known to be polymorphic, whether multiple structures have been done or not. 

Bernstein, J. Polymorphism in Organic Crystals, Oxford University Press, Oxford 2002. 

Bernstein J (2002) Polymorphism in organic crystals. lUCR Monograph on Crystallography, No. 14. Qarendon Press, Oxford... 

A recent summary of studies of polymorphism in organic crystals suggests that nearly all organic substances can crystallize in different crystal forms, whose relative stability is a function of temperature (and pressure). On the other hand, the simultaneous appearance of different polymorphs at room conditions is a much more sparse phenomenon. The common saying, based on a statement by McCrone, that the number of polymorphs for a given organic compound is proportional to the time and money spent in looking for them, should be completed by at variable temperature and pressure . 

Bernstein, J. (1993). Crystal growth, polymorphism and structure-property relationships in organic crystals. J. Phys. D, 26, B66-76. [189]... 

The investigation of different rotational isomers of the same compound in different crystal forms polymorphs) is also an efficient tool in elucidating intermolecular interactions. The phenomenon is called conformational polymorphism. The energy differences between the polymorphs of organic crystals are similar to the free energy differences of rotational isomers of many free molecules, viz., a few kilocalories per mole. When the molecules adopt different conformations in the different polymorphs, the change in rotational isomerism is attributed to the influence of the crystal field since the difference in the intermolecular forces is the single variable in the polymorphic systems. 

K. K. Nass, Process Implications of Polymorphism in Organic Compounds, in Particle Design via Crystallization, R. Ramanarayanan, W. Kem, M. Larson, and S. Sikdar, eds., AIChE Symposium Series, 284, 72 (1991). 

Sarma JARP, Desiraju GR (1998) Polymorphism and pseudopolymorphism in organic crystals. A Cambridge Structural Database study. In Seddon KR, Zaworotko MJ (eds). Crystal engineering. The design and applications of functional solids. NATO ASI Series, in press... 

If the metastable polymorph has contact with a solvent then it reverts to the stable polymorph with the passage of time, but it may be indefinitely stable at room temperature under dry conditions. The enthalpy differences between polymorphs of organic crystals are generally only a few kJ/mol. Polymorphs of pure materials are generally close-packed i.e. without appreciable cavities in their structures. The density differences between polymorphs are usually about 1 % or less. 

The process impKcations of polymorphism in organic compounds has been considered by Nass (1991) who outlined some general recommendations for the batch cooling crystallization of a desired polymorph, either stable or metastable. First, it is necessary to isolate and identify each polymorph and to generate solubility data in more than one solvent in order to determine if the system is monotropic or enantiotropic. This information will help in the selection of a solvent for the industrial process, although the ultimate choice will also have to include considerations of process yield, solvent recovery costs, hazards, etc. 

The first observation of polymorphism in organic materials is attributed to Friedrich Wohler and Justus von Liebig, when in 1832, they examined a boiling solution of benzam-ide on cooling the benzamide initially crystallized as silky needles, but on standing, these were slowly replaced by rhombic crystals. Present day analysis identifies three polymorphs for benzamide. The least stable one, formed by flash cooling is the orthorhombic form 11. This type is followed by the monoclinic form III (observed by Wohler/Liebig). The most... 

Sarma, J. A. R. R, and Desiraju, G. R. 1999. Polymorphism and pseudopolymorphism in organic crystals A Cambridge Stmctural Database study. In Crystal Engineering The Design and Application of Functional Solids. Eds. K. R. Seddon and M. Zaworotko. Kluwer Academic Publishers, Dordrecht, The Netherlands, 325-356. 

Cf. e.g. the reviews on Conformational Polymorphism by J. Berstein in Organic Solid State Chemistry (Ed. G. R. Desiraju), Elsevier Amsterdam 1987, p. 471 or by G. R. Desiraju, Crystal Engineering, Material Science Monographs 54, Elsevier, Amsterdam 1989, p. 285. 

Scheme 5 shows a group of alkynylgold(i) complexes for which the studies focused on the UV-VIS electronic absorption and emission properties. Most of these compounds are of the type [(L)AuC=CR], for which the methods of synthesis have been summarized above. The products were found to show phosphorescence in various polymorphs and crystal forms of solvates. Although there are no metallophilic interactions discernible in the crystal between most of the monomers due to the steric effect of the large tertiary phosphines, there is nevertheless strong excitonic coupling based on other weak interactions, which depend on the organization of the molecules in the crystal.105,106... 

II, and III), two were monohydrates (termed a-monohydrate and /3-monohydrate) and one was a ferf-butylamine disolvate. The differences in the powder patterns of the phases were readily evident (Table 1). This study demonstrates the unique ability of x-ray diffractometry for the identification of (1) anhydrous compound existing in both crystalline and amorphous states, (2) different polymorphic forms of the anhydrate, (3) the existence of solvates where the solvent of crystallization is water (hydrate) or an organic solvent (in this case, /m-butylamine), and (4) polymorphism in the hydrate. 

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