Cluster-based redox responsive super-atomic MRI contrast agents
Jaclyn Brusso
Professor, Department of Chemistry and Biomolecular Sciences
University of Ottawa
Wednesday, November 6, 2024
1 p.m.
In-person: C2-361
Abstract: Transition metal molecular clusters hold great promise as MRI probes, where careful selection of chemical design elements can afford control over the size, shape and total spin state of the contrast agent molecule. A key characteristic of transition metal molecular clusters that can endow these contrast agents with advanced in situ reactivity to biomolecular changes in their environment is that the collection of metal ions within the cluster are linked electronically and can act as a single entity. To date, the potential of transition metal molecular clusters as MRI contrast agents have not been realized due to the problem of cluster dissociation/speciation in biological media. To resolve this challenge, we have employed the N-2-pyrimidylimidoyl-2-pyrimidylamidine chelate to selectively bind 3d metal ions to form highly stable mixed metal clusters. This presentation will focus on these biologically stable chelates, in which the microenvironment-responsive chemical activities of our mixed metal clusters enable us to map biochemical redox potentials spanning reducing and oxidizing environments. Through spectroscopic, electrochemical and magnetic analysis along with in vitro and in vivo studies, the application of iron and manganese homo- and heterometallic triskelion-shaped metal clusters as MRI contrast agents capable of mapping tumor redox status through a simple T1w/T2w ratiometric approach will be demonstrated. The contrast agent design strategy presented introduces heteropolynuclear transition metal complexes suitable for semi-quantitative in vivo MR imaging of tissue redox status and opens up new avenues for non-invasive characterization of biochemical microenvironments by MRI.
Figure: Molecular structures (top) and colour-coded mapping of tumor xenograft redox status (bottom) for FeMn3 (left) and MnMn3 (right).
Jaclyn Brusso obtained her PhD from the University of Waterloo under the direction of Richard Oakley in 2006. Following an NSERC Postdoctoral Fellowship with Dmitrii Perepichka at McGill University and then with Steven Holdcroft’s group at Simon Fraser University, Jaclyn joined the Department of Chemistry at the University of Ottawa in 2010. Her research program focuses on addressing key challenges in the development of smaller, lighter, cheaper and more efficient optical, magnetic and electronic materials. Through the design and development of new organic/inorganic materials, which they tailor at the molecular level, they aim to understand and ultimately control self-assembly at the nanoscale. Jaclyn has received numerous awards for her scientific contributions, has published over 75 peer-reviewed articles and has been recognized for her excellent aptitude for innovation and academic leadership. She is actively involved within the scientific community on many levels, dedicating time and effort to community and youth outreach activities (e.g., Soapbox Science, Project Pulse Spark, Women in STEM, Science Rendezvous, PopChem).