Angewandte Chemie International Edition

Cover image for Vol. 56 Issue 47

Editor: Neville Compton; Editor Emeritus: Peter Gölitz

Online ISSN: 1521-3773

Associated Title(s): Angewandte Chemie, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemistryOpen, ChemPhotoChem, ChemPlusChem, Zeitschrift für Chemie

Press Release

For full article and contact information, see Angew. Chem. Int. Ed. 2003, 42 (47), 5889—5892

No. 47/2003

Twisted Hat

On the way to a tailored contrast agent for nuclear spin tomography

Nuclear spin tomography (or MRI), whose developers received the Nobel Prize in medicine this year, has developed into an important diagnostic procedure. The contrast agents used for this are complexes of the rare-earth metal gadolinium. American researchers have now gained some important insights into the optimization of these contrast agents.

Nuclear spin tomography uses the "spin" (intrinsic angular momentum) of hydrogen atom nuclei (protons). The spins align themselves in a strong magnetic field, but a pulsed radio wave causes them to "flip" in the opposite direction. After the pulse, the spins release electromagnetic waves as they fall back to their ground state (relaxation). This signal depends on the concentration of hydrogen and the relaxation times, which differ for different tissue types. Contrast agents are used to increase the contrast, and these influence the relaxation times of the protons in water molecules. The agents of choice are gadolinium ions, whose seven unpaired electrons induce a strong alternating electromagnetic field, which "shakes" the spins of neighboring water molecules, causing them to return to their ground state more quickly. However, gadolinium ions have toxic effects and they need to be well protected—within a complex. A. Dean Sherry and his team are using a large carbon-nitrogen ring with arms to contain the ion. The gadolinium is held fast by four nitrogen atoms from the ring and four oxygen atoms from the arms, and sits within these ligands as if in a hat. On the "open" side, there is room for one water molecule. In order for the contrast agent to function optimally, the water molecule must disappear as quickly as possible after "relaxing", so as to make room for another. The turnover time depends on the structure of the complex.

Each set of four nitrogen and four oxygen atoms in the complex makes a square. This results in two possible configurations, an antiprism and a twisted antiprism, which differ in the degree of rotation of the two squares relative to each other. These can be interconverted by a "flip" of the ring and a rotation of the arms. Do the two forms hold onto water molecules for different lengths of time? Mark Woods of Sherry’s group attached "stoppers" to the ring and each arm in order to prevent flipping and rotation. By selecting the right configuration of the arms, both forms could be obtained, and water molecules did indeed spend considerably less time in the twisted antiprism than in the antiprism. This represents an important step toward a targeted design for nuclear spin contrast agents.