NMR sheds new light on polymorphic forms in pharmaceutical compounds

Researchers made use of the UK's largest solid-state NMR magnets, housed at the University of Warwick, to carry out the study in collaboration with Astra Zeneca and GlaxoSmithKline.

The analytical methods look directly at the hydrogen and nitrogen atoms that are at the heart of so-called hydrogen bonds which control how organic molecules self-assemble into different three-dimensional solid-state structures.

Professor Steven P. Brown from the Department of Physics at the University of Warwick said: "Screening polymorphic forms of active pharmaceutical ingredients is a key part of pharmaceutical development."

"The combination of high magnetic field and novel rf pulse methodologies are allowing us to look by NMR with high precision at the distinct intermolecular hydrogen bonding arrangements that help us understand why pharmaceutical molecules adopt different polymorphic forms."

"By using the University of Warwick's state-of-the-art facilities we are able to shed new light on this complex area."

More information: The two papers are available to view at the following links:

Bradley et al. J. Pharm. Sci. http://onlinelibrary.wiley.com/doi/10.1002/jps.23078/abstract
Tatton et al., CrystEngComm http://pubs.rsc.org/en/Content/ArticleLanding/2012/CE/c2ce06547a

Provided by University of Warwick (news : web)

Fingerprinting uranium: X-rays identify mobile, stationary forms of atomic pollutant

"This is the first time that anyone has formalized this approach and showed how broadly useful it is," said Dr. Eugene Ilton, a PNNL geochemist.

Uranium poses risks around the world. At one U.S. site, 200,000 kg or about 220 tons of uranium entered the environment. Whether the radionuclide travels to nearby water sources depends on its oxidation state, the number of electrons around the atom. Ilton and Bagus' method accurately pinpoints uranium's oxidation state. Using this method allows scientists to more accurately predict the atomic pollutant's behavior.

This technique begins with XPS, which is used commercially and scientifically to determine the chemical state, elemental composition, and other details about materials. The instrument directs a beam of X-rays at the sample, which is placed under ultra high vacuum. The beam excites electrons within the sample, forcing the electrons to leap off. Sensors within the instrument measure the number of electrons that escape at a particular kinetic energy.

The data is plotted as the number of electrons versus kinetic energy, or binding energy, forming peaks that are characteristic of an element in the material. The kinetic energy and binding energy are related by a simple formula discovered by Albert Einstein. Scientists can interpret the size, shape, and energy of the peaks to characterize the samples. The peaks fall roughly into two categories: primary and secondary. The primary peaks are usually larger than the secondary peaks, which are called satellites.

Ilton and Bagus analyzed samples containing very dilute amounts of uranium using the XPS in EMSL and also did a broad literature search on previous XPS work on uranium compounds. They focused on the satellite structures and showed that the energy separation between the satellite and primary peaks was diagnostic of uranium oxidation states over a broad range of  compounds with very different compositions.

This led to the development of a methodical process for taking XPS data and determining the oxidation state of uranium. While the team was not the first to use uranium satellite structures in this way, they showed that the method is broadly applicable to a wide range of uranium-bearing materials.

"Using XPS can provide a definitive fingerprint of the oxidation state of uranium," said Ilton.

Ilton and Bagus are working on theoretical approaches to pull more information from the XPS spectra. The data they provide can be used in other studies examining the oxidation state of uranium and other metal compounds.

More information: ES Ilton and PS Bagus. 2011. "XPS Determination of Uranium Oxidation States." Surface and Interface Analysis 143(13):1549-1560. DOI: 10.1002/sia.3836

Provided by Pacific Northwest National Laboratory (news : web)