PROJECT SUMMARY Magnetic resonance imaging (MRI) is a non-invasive imaging technique that can provide information on the anatomy, function, and metabolism of tissues in vivo. MRI scans make use of the two hydrogen atoms in water to generate the image. Unfortunately, the intrinsic contrast provided by the water T1 and T2 relaxation times, and changes in their values brought about by tissue pathology, are often too limited to enable a sensitive and specific diagnosis. For that reason, increasing use is made of MRI contrast agents that alter the image contrast following intravenous injection. Depending on the chemical composition, molecular structure, and overall size of the contrast agents, the in vivo distribution volume and pharmacokinetic properties vary widely with little control, and this largely determines their use in specific diagnostic tests. Additionally, traditional gadolinium-based contrast agents have been implicated as potential nephrotoxins and neurotoxins. To overcome these limitations the proposed research will focus on designing dynamic, activatable, or ‘intelligent’ MRI contrast agents based on iron(II) complexes that undergo thermally induced spin-state crossover to provide local temperature data and tissue contrast. These novel contrast agents will allow for the monitoring of tissue environments with greater spatial and temporal data feedback. The complexes will also allow for enhanced signal resolution at therapeutically relevant temperatures for patients undergoing high-temperature tumor ablation. We will design Fe(II) crossover complexes that can exist in an ‘on’ or ‘off’ state depending on the local temperature of their physiological environment, providing an added layer of detail in real-time MRI scans. Additionally, we propose attaching these contrast agents to known peptide binders for discrete tissue types or cell and protein receptors. The ability to target specific tissue types and direct accumulation of these contrast agents would enhance imaging and lead to greater patient outcomes. The proposed research will also have a tremendous positive impact on the research environment at Salisbury University through the engagement of undergraduate students in research projects at the forefront of synthesis of MRI contrast agents, likely propelling them to future careers in the chemical and biomedical sciences.