Issue Date: September 7, 2009
Crystalline Wiggle Room
A study of crystalline forms of the antibiotic clarithromycin has revealed that certain nonporous organic solids can somehow absorb small molecules such as water and CO2 into void spaces throughout the crystal lattice, even though no suitably sized transport channels exist (J. Am. Chem. Soc., DOI: 10.1021/ja904658p). The finding implies that the organic solid state may not be as solid as X-ray crystal structure studies indicate, and it could impact how drugs are patented, as well as open up new possibilities for gas separation and storage.
Jerry L. Atwood of the University of Missouri, Columbia, and coworkers observed that pristine clarithromycin crystals left exposed to air or soaked in water wound up with H2O molecules isolated in void spaces in the crystals, creating a new crystalline form of the drug. The researchers also found that clarithromycin crystals selectively absorb CO2, but not H2, N2, or CH4. The research follows the Atwood group’s earlier studies on the diffusion of small molecules into seemingly nonporous calixarene-based supramolecular solids.
Exactly how water and CO2 can diffuse into a hydrophobic, nonporous crystalline material like clarithromycin is a mystery, Atwood says. The size of the voids does not seem to be the basis for the phenomenon, he notes, because gases such as N2 are not absorbed. Atwood thinks some dynamic process involving crystal-lattice flexibility must be at play that leads to a single-crystal-to-single-crystal transition.
“This is not the first example of these kinds of transitions, but they are extremely rare,” says supramolecular chemist Jonathan W. Steed of Durham University, in England. “Atwood’s work suggests that they remain rare because scientists have not looked for them properly.”
The finding could have legal and financial ramifications for pharmaceutical companies, which base their drug patents on specific crystalline polymorphs. For example, discovery of a new polymorph, say, a previously unknown hydrated form, could be the basis of a separate drug patent. And although Atwood doesn’t envision using an antibiotic for gas separations, he believes a wider range of organic solids should now be tested for such applications.
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