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Science  02 Mar 2001:
Vol. 291, Issue 5509, pp. 1665
DOI: 10.1126/science.291.5509.1665c

Many molecules can exist in several crystal forms (polymorphs) possessing different properties such as density, melting point, and vibrational spectra. It is often difficult to obtain crystals of a particular polymorph, and some have been known to “disappear”—after being obtained routinely for a while, suddenly difficulties will be encountered when trying to make them.

Henck et al. have developed a strategy for the rational analysis and control of the conditions under which certain polymorphs form—including those that have formerly “disappeared.” In a case study of the benzocaine:picric acid system, a low-melting polymorph of this system had been reported to have “disappeared.” Optical and thermomicroscopy were used to derive a phase diagram to guide crystal growth for examination by x-ray crystallography. The authors were consistently able to produce crystals of the “disappearing” polymorph. This strategy should now be applicable more generally to identify polymorphs, to develop robust procedures for obtaining individual polymorphs, and to prepare individual crystals for structure determination. — JU

J. Am. Chem. Soc., in press.

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