About half of chemotherapeutic treatments for cancer currently use platinum coordination complexes. Cisplatin was the first platinum compound discovered to have anticancer activity, however it can have toxic side effects. Such drugs have been in use for a long time, and resistance to them is fast becoming an issue. It is vital that new generations of anticancer drug complexes are discovered which are less toxic but still active against resistant cancers. ISIS and Diamond Light Source have collaborated with a team from the Department of Chemistry at the University of Warwick, to examine metals similar to platinum to develop a low-dose therapy. They landed on rhodium, and carried out studies on organometallic rhodium compounds, which have unique rhodium-carbon bonds.
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Now, the team are trying to find out about the molecular mechanisms of the drug. At Diamond, they employed nanometer-resolved X-ray imaging to identify rhodume-induce damage to organelles such as mitochondria, and determine metal distribution in cells to find target sites. At ISIS, they utilised the TOSCA beamline to observe the dynamics of the metal complexes which are not static, as often assumed. There are large amounts of energy in bond vibrations of the complex, which can contribute greatly to the way they react. This energy enables certain catalytic properties, like the ability to repeat reactions.
The team plans to use the information gained on dynamics and vibrations to improve the design of the drug. Dynamics and vibrations are critical for the transmission of the drug through the cell membrane. The researchers described the drug as “a nanobot explorer", as the vibrations of the machine contribute to its function. Neutron data provide the only method of developing a complete picture of the vibrational activity of the complex. To utilize this data, the team are carrying out computational modelling which complements vibrational spectroscopy, with the group of Juliusz and Volker Schünemann (Kaiserslautern, TUK).
This generation of organometallic cancer drugs will hopefully decrease patient discomfort due to reduced toxicity and provide a better defense against resistant cancers. Neutron data from ISIS beamlines is vital in optimizing their design.
