Asymmetry-enhanced 59Co NMR thermometry in Co(iii) complexes.

Design strategies for molecular thermometers by magnetic resonance are essential for enabling new noninvasive means of temperature mapping for disease diagnoses and treatments. Herein we demonstrate a new design strategy for thermometry based on chemical control of the vibrational partition function. To do so, we performed variable-temperature 59Co NMR investigations of four air-stable Co(iii) complexes: Co(accp)3 (1), Co(bzac)3 (2), Co(tBu2-acac)3 (3), and Co(acac)3 (4) (accp = 2-acetylcyclopentanonate; bzac = benzoylacetonate; tBu2-acac = 2,2,6,6-tetramethyl-3,5-heptanedionate and acac = acetylacetonate). We discovered 59Co chemical shift temperature sensitivity (Δδ/ΔT) values of 3.50(2), 3.39(3), 1.63(3), and 2.83(1) ppm °C-1 for 1-4, respectively, at 100 mM concentration. The values observed for 1 and 2 are new records for sensitivity for low-spin Co(iii) complexes. We propose that the observed heightened sensitivities for 1 and 2 are intimately tied to the asymmetry of the accp and bzac ligands versus the acac and tBu2-acac ligands, which enables a larger number of low-energy Raman-active vibrational modes to contribute to the observed Δδ/ΔT values.

Record Chemical-Shift Temperature Sensitivity in a Series of Trinuclear Cobalt Complexes.

Designing spins that exhibit long-lived coherence and strong temperature sensitivity is central to designing effective molecular thermometers and a fundamental challenge in the chemistry/quantum-information space. Herein, we provide a new pathway to both properties in the same molecule by designing a nuclear spin, which possesses a robust spin coherence, to mimic the strong temperature sensitivity of an electronic spin. This design strategy is demonstrated in the group of trinuclear Co(III) spin-crossover compounds [(CpCo(OP(OR)2)3)2Co](SbCl6) where Cp = cyclopentadienyl and R = Me (1), Et (2), i-Pr (3), and t-Bu (4). Nuclear magnetic resonance analyses of the 59Co nuclear spins reveal 59Co chemical-shift temperature sensitivity (Δδ/ΔT) values that span from 101(1) ppm/°C in 1 to 149(1) ppm/°C in 2 and 150(2) ppm/°C in 4, where the latter two are record temperature sensitivities for any nuclear spin. Additionally, complexes 2 and 4 have T2* values of 74 and 78 µs in solution at ambient temperatures surpassing those from electron-spin-based complexes, which typically display long coherence times only at extremely low temperatures. Our results suggest that spin-crossover phenomena can enable electron-spin-like temperature sensitivities in nuclear spins while retaining robust coherence times at room temperature.

Ligand design of zero-field splitting in trigonal prismatic Ni(II) cage complexes.

Complexes of encapsulated metal ions are promising potential metal-based electron paramagnetic resonance imaging (EPRI) agents due to zero-field splitting. Herein, we synthesize and magnetically characterize a series of five new Ni(II) complexes based on a clathrochelate ligand to provide a new design strategy for zero-field splitting in an encaged environment. UV-Vis and X-ray single-crystal diffraction experiments demonstrate slight physical and electronic structure changes as a function of the differing substituents. The consequence of these changes at the remote apical and sidearm positions of the encaging ligands is a zero-field splitting parameter (D) that varies over a large range of 11 cm-1. These results demonstrate a remarkable flexibility of the zero-field splitting and electronic structure in nickelous cages and give a clear toolkit for modifying zero-field splitting in highly stable ligand shells.

Isotopomeric Elucidation of the Mechanism of Temperature Sensitivity in 59Co NMR Molecular Thermometers.

Understanding the mechanisms governing temperature-dependent magnetic resonance properties is essential for enabling thermometry via magnetic resonance imaging. Herein we harness a new molecular design strategy for thermometry─that of effective mass engineering via deuteration in the first coordination shell─to reveal the mechanistic origin of 59Co chemical shift thermometry. Exposure of [Co(en)3]3+ (1; en = ethylenediamine) and [Co(diNOsar)]3+ (2; diNOsar = dinitrosarcophagine) to mixtures of H2O and D2O produces distributions of [Co(en)3]3+-dn (n = 0-12) and [Co(diNOsar)]3+-dn (n = 0-6) isotopomers all resolvable by 59Co NMR. Variable-temperature 59Co NMR analyses reveal a temperature dependence of the 59Co chemical shift, Δδ/ΔT, on deuteration of the N-donor atoms. For 1, deuteration amplifies Δδ/ΔT by 0.07 ppm/°C. Increasing degrees of deuteration yield an opposing influence on 2, diminishing Δδ/ΔT by -0.07 ppm/°C. Solution-phase Raman spectroscopy in the low-frequency 200-600 cm-1 regime reveals a red shift of Raman-active Co-N6 vibrational modes by deuteration. Analysis of the normal vibrational modes shows that Raman modes produce the largest variation in 59Co δ. Finally, partition function analysis of the Raman-active modes shows that increased populations of Raman modes predict greater Δδ/ΔT, representing new experimental insight into the thermometry mechanism.

EXAFS investigations of temperature-dependent structure in cobalt-59 molecular NMR thermometers.

Cobalt-59 nuclei are known for extremely thermally sensitive chemical shifts (δ), which in the long term could yield novel magnetic resonance thermometers for bioimaging applications. In this manuscript, we apply extended X-ray absorption fine structure (EXAFS) spectroscopy for the first time to probe the exact variations in physical structure that produce the exceptional thermal sensitivity of the 59Co NMR chemical shift. We apply this spectroscopic technique to five Co(iii) complexes: [Co(NH3)6]Cl3 (1), [Co(en)3]Cl3 (2) (en = ethylenediamine), [Co(tn)3]Cl3 (3) (tn = trimethylenediamine), [Co(tame)2]Cl3 (4) (tame = 1,1,1-tris(aminomethyl)ethane), and [Co(diNOsar)]Cl3 (5) (diNOsar = dinitrosarcophagine). The solution-phase EXAFS data reveal increasing Co-N bond distances for these aqueous complexes over a ∼50 °C temperature window, expanding by Δr(Co-N) = 0.0256(6) Å, 0.0020(5) Å, 0.0084(5) Å, 0.0006(5) Å, and 0.0075(6) Å for 1-5, respectively. Computational analyses of the structural changes reveal that increased connectivity between the donor atoms encourages complex structural variations. These results imply that rich temperature-dependent structural variations define 59Co NMR thermometry in macrocyclic complexes.

Ligand Control of 59Co Nuclear Spin Relaxation Thermometry.

Studying the correlation between temperature-driven molecular structure and nuclear spin dynamics is essential to understanding fundamental design principles for thermometric nuclear magnetic resonance spin-based probes. Herein, we study the impact of progressively encapsulating ligands on temperature-dependent 59Co T 1 (spin-lattice) and T 2 (spin-spin) relaxation times in a set of Co(III) complexes: K3[Co(CN)6] (1); [Co(NH3)6]Cl3 (2); [Co(en)3]Cl3 (3), en = ethylenediamine); [Co(tn)3]Cl3 (4), tn = trimethylenediamine); [Co(tame)2]Cl3 (5), tame = triaminomethylethane); and [Co(dinosar)]Cl3 (6), dinosar = dinitrosarcophagine). Measurements indicate that 59Co T 1 and T 2 increase with temperature for 1-6 between 10 and 60 °C, with the greatest ΔT 1/ΔT and ΔT 2/ΔT temperature sensitivities found for 4 and 3, 5.3(3)%T 1/°C and 6(1)%T 2/°C, respectively. Temperature-dependent T 2* (dephasing time) analyses were also made, revealing the highest ΔT 2*/ΔT sensitivities in structures of greatest encapsulation, as high as 4.64%T 2*/°C for 6. Calculations of the temperature-dependent quadrupolar coupling parameter, Δe 2 qQ/ΔT, enable insight into the origins of the relative ΔT 1/ΔT values. These results suggest tunable quadrupolar coupling interactions as novel design principles for enhancing temperature sensitivity in nuclear spin-based probes.

Influence of ligand encapsulation on cobalt-59 chemical-shift thermometry.

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.