Spin-crossover and high-spin iron(ii) complexes as chemical shift ¹⁹F magnetic resonance thermometers

The potential utility of paramagnetic transition metal complexes as chemical shift ¹⁹F magnetic resonance (MR) thermometers is demonstrated. Further, spin-crossover Fe^II complexes are shown to provide much higher temperature sensitivity than do the high-spin analogues, owing to the variation of spin state with temperature in the former complexes. This approach is illustrated through a series of Fe^II complexes supported by symmetrically and asymmetrically substituted 1,4,7-triazacyclononane ligand scaffolds bearing 3-fluoro-2-picolyl derivatives as pendent groups (L_x). Variable-temperature magnetic susceptibility measurements, in conjunction with UV-vis and NMR data, show thermally-induced spin-crossover for [Fe(L₁)]²⁺ in H₂O, with T_1/2 = 52(1) °C. Conversely, [Fe(L₂)]²⁺ remains high-spin in the temperature range 4-61 °C. Variable-temperature ¹⁹F NMR spectra reveal the chemical shifts of the complexes to exhibit a linear temperature dependence, with the two peaks of the spin-crossover complex providing temperature sensitivities of +0.52(1) and +0.45(1) ppm per °C in H₂O. These values represent more than two-fold higher sensitivity than that afforded by the high-spin analogue, and ca. 40-fold higher sensitivity than diamagnetic perfluorocarbon-based thermometers. Finally, these complexes exhibit excellent stability in a physiological environment, as evidenced by ¹⁹F NMR spectra collected in fetal bovine serum.