How does aspirin crystallize?

Dec 22, 2006

When you get a headache, you probably reach for aspirin. What is giving researchers a headache is the question of the crystal structure of aspirin. Is there another form on top of the long-known one?

A team of scientists from Denmark, Germany, and India seems to have solved this controversial puzzle: yes, there is a second structure--but it does not exist as a pure form. "The two crystalline forms of aspirin are so closely related," explains the research team of Andrew D. Bond, Roland Boese and Gautam R. Desiraju in Angewandte Chemie, "that they form structures containing domains of both crystal types."

In 2004, computer calculations had indicated that while the long-known crystal structure of aspirin (form I) is definitely one of the most stable forms, another version might exist that is just as stable, though it had not yet been discovered--a clear challenge to researchers in the field. The difference between the proposed structures is slight: both have identical layers containing molecules grouped into pairs, but these layers are arranged differently in the two different structures. In 2005, researchers in the USA announced the discovery of the predicted structure (form II). But was this merely an artifact?

"We can now clear this matter up," say Bond, Boese and Desiraju, after very careful examination of aspirin crystals.

"Aspirin has a tendency to crystallize with an unusual intergrown structure. The same single crystal contains domains with both arrangements lying side by side." The distribution and ratio of the domains are variable but limited. Whereas a pure form I exists, it has so far only been possible to obtain crystals containing a maximum of 85 % form II. The ratio of the two domains within crystals produced under identical conditions seems to be roughly constant.

This discovery upends fundamental principles and requires new concepts: chemists previously understood "polymorphism" to mean that a molecule can take on one or another packing arrangement in the crystalline state; a single crystal of a specific chemical substance is either one polymorph or the other. Aspirin is the first case in which two different "polymorphic" structures exist in one single crystal. So is aspirin polymorphic or not? Should the definition of polymorphism be updated? Such questions are not just philosophical in nature, but could have tangible implications in patent law, because each polymorph of a compound is viewed as a separate patentable substance.

Citation: Angewandte Chemie International Edition 2007, 46, No. 4, 615–617, doi: 10.1002/anie.200602378

Source: John Wiley & Sons

Explore further: A refined approach to proteins at low resolution

add to favorites email to friend print save as pdf

Related Stories

Visualizing the structures of molecules

Dec 05, 2012

Hitoshi Goto and colleagues have developed high performance molecular simulation tools to study the 3D arrangement of molecules, enabling better design of medicinal and agricultural drugs which are more effective ...

NASA Instrument Will Identify Clues to Martian Past

Jun 28, 2010

(PhysOrg.com) -- NASA's Curiosity rover, coming together for a late 2011 launch to Mars, has a newly installed component: a key onboard X-ray instrument for helping the mission achieve its goals. Researchers ...

Gene therapy could expand stem cells' promise

May 21, 2009

Once placed into a patient's body, stem cells intended to treat or cure a disease could end up wreaking havoc simply because they are no longer under the control of the clinician.

Recommended for you

A refined approach to proteins at low resolution

8 hours ago

Membrane proteins and large protein complexes are notoriously difficult to study with X-ray crystallography, not least because they are often very difficult, if not impossible, to crystallize, but also because ...

Base-pairing protects DNA from UV damage

10 hours ago

Ludwig Maximilian University of Munich researchers have discovered a further function of the base-pairing that holds the two strands of the DNA double helix together: it plays a crucial role in protecting ...

Smartgels are thicker than water

11 hours ago

Transforming substances from liquids into gels plays an important role across many industries, including cosmetics, medicine, and energy. But the transformation process, called gelation, where manufacturers ...

Separation of para and ortho water

Sep 18, 2014

(Phys.org) —Not all water is equal—at least not at the molecular level. There are two versions of the water molecule, para and ortho water, in which the spin states of the hydrogen nuclei are different. ...

User comments : 0