丁香园AV

1) Mechanisms and biological interactions of ruthenium anticancer compounds

We are studying the in vitro and in vivo behaviour of Ru(III) chemotherapeutics and their mechanisms of action. Recently, we have shown the importance of serum-protein interactions to the speciation of these compounds, which lead to the maintenance of their Ru(III) oxidation state and influence aquation and oligomerization processes.

2) Design and synthesis of new metal-based anticancer drugs targeting specific biomolecule interactions

We are using ligand design to develop new Ru complexes which target hydrophobic protein binding. Hydrophobic interactions of Ru complexes with human serum albumin are a current area of focus. Ultimately, we are seeking to develop metallodrug-protein conjugates as selective anticancer agents.

3) Development of redox-activated metal-based anticancer compounds for tumour targeting

The combination of redox-active metal centres with redox-active ligands promises to produce new anticancer drug candidates which can generate ligand radicals and reactive oxygen species, while also interacting with DNA. We are developing complexes of several metal ions, which are activated in hypoxic tumour environments for targeted anticancer activity.

4) Application of EPR spectroscopy to the mechanisms of paramagnetic metallodrug candidates

Electron paramagnetic resonance (EPR) spectroscopy provides unique insight into the structure and chemical properties of paramagnetic species. We are using EPR to study the mechanisms of paramagnetic anticancer metallodrugs, such as those containing Ru(III). Using this technique we can characterize interactions with proteins, DNA, and components of serum and whole cells. We are also using EPR to determine the production of reactive oxygen species from redox-active metal complexes.

5) Structure and Reactivity of paramagnetic species, such as radicals, spin traps, reactive oxygen species

The 丁香园AV EPR/ENDOR facility enables studies of a wide array paramagnetic species. To date, this has included: 

• Radical reactions
• Paramagnetic organometallic compounds
• Redox-active metal complexes
• Spin trapping of reactive intermediates
• Spectroelectrochemistry

For access to this facility and potential collaborations, please contact Charles Walsby.