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

The potential utility of paramagnetic transition metal complexes as chemical shift (19)F 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(L(1))](2+) in H(2)O, with T (1/2) = 52(1) °C. Conversely, [Fe(L(2))](2+) remains high-spin in the temperature range 4–61 °C. Variable-temperature (19)F 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 H(2)O. 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 (19)F NMR spectra collected in fetal bovine serum.