Research – The Wilson Research Group

Ligand Design for Metallic Radioisotopes

Radioactive decay can be harnessed for both therapeutic and diagnostic applications. Three components are generally required: (1) the radioisotope that relays diagnostic information via penetrating radiation or therapeutic effects via non-penetrating radiation; (2) a targeting agent that delivers the radioisotope to the desired biological site; (3) and a chelating agent and linker that stably binds the radioisotope en route to its target. Often, the lack of a suitable chelating agent for a given radioisotope will limit its further clinical use. The Wilson Group works on the design of new ligands that are capable of chelating novel metallic radioisotopes with the aim of expanding the tool box of nuclear medicine.

Medicinal Properties of Ruthenium and Osmium Complexes

Ischemia/reperfusion injury (IRI) is a significant contributor to the high mortality rate of heart attacks, traumatic brain damage, and organ transplant. Following hypoxia, upon reoxygenation, flooding of the
mitochondria with calcium via the mitochondrial calcium uniporter (MCU) is known to release reactive oxygen species (ROS) causing cell death. Our goal in this project is to prepare effective mitochondrial Ca2+ uptake inhibitors for the prevention of IRI. We have prepared and characterized novel nitrido-bridged Ru complexes (Ru265) and have further shown that it is capable of inhibiting calcium uptake and protecting
cells in an in vitro model of ischemia/reperfusion. We are working to further exploit Ru265’s functionality by introducing new axial ligands and substituting metal centers, to make Ru265 analogues with improved chemical and biological properties.

Platinum-based complexes have enjoyed widespread success as anticancer drugs. More recently, ruthenium complexes, and to a lesser extent osmium complexes, have demonstrated therapeutic potential. The utility of ruthenium complexes for cancer treatment is reflected by the progression of NAMI-A and KP 1019 (see below) to clinical trials for their anti-metastatic and cytotoxic properties, respectively. The Wilson Group is pursuing the design and synthesis of novel ruthenium and osmium compounds that exhibit unique biological mechanisms of action. We are also exploring strategies to expand the scope of these metallopharmaceuticals towards other diseases.

Bioinorganic Medicinal Chemistry

The Wilson Group explores the use of metal ions and complexes for medicinal purposes. The novel properties of metal ions provide opportunities to discover new therapeutic and diagnostic modalities that are not accessible to organic molecules. The unique ligand substitution reactions, magnetic properties, and radioactivity of metal ions are exploited currently in pharmaceutical agents, such as cisplatin (cis-diamminedichlorplatinum(II)), Dotarem ([Gd(DOTA)]^-1), and ^99mTc-Cardiolite.