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Abstract

Thermometry via magnetic resonance imaging (MRI) would provide a powerful noninvasive window into physiological temperature management. Cobalt-59 nuclear spins demonstrate exceptional temperature dependence of their NMR chemical shifts, yet the insight to control this dependence via molecular design is lacking. We present the first systematic evidence that encapsulation of this spin system amplifies the temperature sensitivity. We tested the temperature dependence of the 59Co chemical shift (Δδ/ΔT) in a series of five low-spin cobalt(iii) complexes as a function of increasing encapsulation within the 1st coordination sphere. This study spans from [Co(NH3)6]Cl3, with no interligand connectivity, to a fully encapsulated dinitrosarcophagine (diNOsar) complex, [Co(diNOsar)]Cl3. We discovered Δδ/ΔT values that span from 1.44(2) ppm °C–1 in [Co(NH3)6]Cl3 to 2.04(2) ppm °C–1 in [Co(diNOsar)]Cl3, the latter among the highest for a molecular complex. The data herein suggest that designing 59Co NMR thermometers toward high chemical stability can be coincident with high Δδ/ΔT. To better understand this phenomenon, variable-temperature UV-Vis, 59Co NMR relaxation, Raman spectroscopic, and variable-solvent investigations were performed. Data from these measurements highlight an unexpected impact of encapsulation – an increasingly dynamic and flexible inner coordination sphere. These results comprise the first systematic studies to reveal insight into the molecular factors that govern Δδ/ΔT and provide the first evidence of 59Co nuclear-spin control via vibrational means.

Results and discussion

Precise determination of the sensitivity of the 59Co NMR peak to temperature (Δδ/ΔT) was achieved via linear regression of the temperature-dependent data (see , S8, and Table S2). These analyses revealed Δδ/ΔT values for K3[Co(CN)6] and 1–5, respectively, of 1.44(1), 1.44(2), 1.38(1), 1.30(2), 1.71(1), and 2.04(2) ppm °C–1. These values are within the ranges of sensitivity reported for the few 59Co NMR thermometers,–, but it's worth noting that, to the best of our knowledge, the Δδ/ΔT of 5 is eclipsed only by Co(acac)3, a molecule that is completely unsuitable for aqueous (e.g. physiological) applications., Most importantly (and surprisingly), these data indicate that the highest sensitivity to changes in temperature is held by the completely encaged complex 5.

Results and discussion

The values of Δδ/ΔT follow an opposing trend to the initial hypothesis, in that 5, with the highest degree of encapsulation, displays the strongest Δδ/ΔT. Complex 4, with the second highest degree of encapsulation, displays the second highest sensitivity of our studied complexes. Yet, a comprehensive trend for all complexes on the basis of encapsulation is not indicated by these data. For example, in 1 and K3[Co(CN)6], the ligand donor atoms are not connected in any manner. Yet, these species demonstrate higher Δδ/ΔT than both 2 and 3, which contain bidentate chelates. Furthermore, the collected data show that electronic structure considerations alone (specifically, Δo) do not govern sensitivity. Here, neither the trend in Δo extracted from UV-Vis (3 < 5 < 1 < 4 < 2 < K3[Co(CN)6]) nor that from the 25 °C 59Co NMR (3 < 1 < 4 < 2 < 5 < K3[Co(CN)6]) reproduce the trend in Δδ/ΔT (see Fig. S9 and Table S3).