Fluorous Liquids for Magnetic Resonance-Based Thermometry with Enhanced Responsiveness and Environmental Degradation

Accurate temperature measurement via magnetic resonance is valuable for both in vitro and in vivo analysis of local tissue for evaluating disease pathology and medical interventions. ¹H MRI-based thermometry is used clinically but is susceptible to error from magnetic field drift and low sensitivity in fatty tissue and requires a reference for absolute temperature determination. As an alternative, perfluorotributylamine (PFTBA), a perfluorocarbon liquid for ¹⁹F MRI thermometry, is based on chemical shift responsiveness and approaches the sensitivity of ¹H MRI thermometry agents; however, environmental persistence, greenhouse gas concerns, and multiple resonances which can lead to MRI artifacts indicate a need for alternative sensors. Using a ¹⁹F NMR-based structure-property study of synthetic organofluorine molecules, this research develops new organofluorine liquids with improved temperature responsiveness, high signal, and reduced nonmagnetically equivalent fluorine resonances. Environmental degradation analysis using reverse-phase HPLC and quantitative ¹⁹F NMR demonstrates a rapid degradation profile mediated via the aryl fluorine core of temperature sensors. Our findings show that our lead liquid temperature sensor, DD-1, can be made in high yield in a single step and possesses an improved responsiveness over our prior work and an 83% increase in aqueous thermal responsiveness over PFTBA. Degradation studies indicate robust degradation with half-lives of less than two hours under photolysis conditions for the parent compound and formation of other fluorinated products. The improved performance of DD-1 and its susceptibility to environmental degradation highlight a new lead fluorous liquid for thermometry applications.