Mollusks point way toward better drugs

From New York City, at the National Meeting of the American Chemical Society

Although a drug’s set chemical structure determines its mechanism of action, its larger crystal structure can change in ways that determine how well the drug dissolves in the gut and how long it will last on the shelf. Adam Matzger of the University of Michigan in Ann Arbor has developed an efficient way to create various crystal structures, known as polymorphs.

When growing polymorphs in the lab, researchers either vary the amount of solvent in a solution of the drug that is undergoing crystallization or tweak the solution’s temperature. But how the crystals form different shapes is a mystery, and repeating a crystallization process doesn’t always produce the same polymorph.

Inspired by the way mollusks use proteins–one of nature’s most versatile types of polymers–to deposit calcium carbonate in their shells, Matzger decided to grow crystals on various synthetic polymers and see what polymorphs emerged. He found that a polymer film determines a polymorph’s ultimate crystal structure by the time the first 10 to 100 drug molecules aggregated on the film. Moreover, different polymers, including familiar ones such as nylon and polyvinyl chloride, yielded different polymorphs.

When Matzger and his colleagues grew acetaminophen crystals using the polymers, the technique produced both of the drug’s known polymorphs, depending on the polymer substrate. The researchers also grew crystals of the epilepsy drug carbamazepine on various polymers and generated four different polymorphs, one of which had never been seen before.

Matzger’s technique could be a boon for drug companies. A drug’s crystal structure can have a huge role in the compound’s behavior in the body.


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