With the help of the world’s most powerful X-ray laser, European XFEL, a research team led by Goethe University Frankfurt and the research centre DESY has achieved an important breakthrough: Using the example of the pharmaceutically active substance 2-thiouracil, they applied a long-established imaging technique to complex molecules for the first time. Although 2-thiouracil is no longer applied therapeutically, it is part of a group of chemically similar active substances that are used today as immunosuppressants or cytostatics. The study shows how UV radiation deforms 2-thiouracil, making it dangerously reactive.
Many biologically important molecules change shape when stimulated by UV radiation. Although this property can also be found in some drugs, it is not yet well understood. Using an innovative technique, an international team involving researchers from Goethe University Frankfurt, the European XFEL in Schenefeld and the Deutschen Elektronen-Synchrotron DESY in Hamburg has elucidated this ultra-fast process, and made it visible in slow motion, with the help of X-ray light. The method opens up exciting new ways of analysing many other molecules.
“We investigated the molecule 2-thiouracil, which belongs to a group of pharmaceutically active substances based on certain DNA building blocks, the nucleobases,” says the study’s last author Markus Gühr, the head of DESY’s free-electron laser FLASH and Professor of Chemistry at University of Hamburg. 2-thiouracil and its chemically related active substances have a sulphur atom, which gives the molecules its unusual, medically relevant properties. “Another special feature is that these molecules become dangerously reactive when exposed to UV radiation.” Studies indicate an increased risk of skin cancer due to this effect.
To better understand what happens during such processes, the research team used an already well-established method, bringing it to a new level by applying the technical possibilities available today. “Coulomb explosion imaging involves irradiating a molecule with intense X-ray pulses, which knock out electrons,” explains Till Jahnke, Professor of Experimental Atomic and Molecular Physics at Goethe University and the study’s first author. “Thereby, the molecule charges up positively and thus becomes unstable, so that it is torn apart within fractions of a second.” By tracking the direction in which the various fragments of the molecule – the atoms – fly apart, it is possible to derive information about the molecule’s structure.
Read more on European XFEL website
Image: The SQS instrument’s COLTRIMS reaction microscope was used to analyze the structural changes of the 2-thiouracil molecule at the European XFEL.
Credit: European XFEL