Low-Spin Fe(III) Macrocyclic Complexes of Imidazole-Appended 1,4,7-Triazacyclononane as Paramagnetic Probes

Two macrocyclic complexes of 1,4,7-triazacyclononane (TACN), one with N-methyl imidazole pendants, [Fe(Mim)]³⁺, and one with unsubstituted NH imidazole pendants, [Fe(Tim)]³⁺, were prepared with a view toward biomedical imaging applications. These low-spin Fe³⁺ complexes produce moderately paramagnetically shifted and relatively sharp ¹H NMR resonances for paraSHIFT and paraCEST applications. The [Fe(Tim)]³⁺ complex undergoes pH-dependent changes in NMR spectra in solution that are consistent with the consecutive deprotonation of all three imidazole pendant groups at high pH values. N-Methylation of the imidazole pendants in [Fe(Mim)]³⁺ produces a complex that dissociates more readily at high pH in comparison to [Fe(Tim)]³⁺, which contains ionizable donor groups. Cyclic voltammetry studies show that the redox potential of [Fe(Mim)]³⁺ is invariant with pH ( E_1/2 = 328 ± 3 mV vs NHE) between pH 3.2 and 8.4, unlike the Fe(III) complex of Tim which shows a 590 mV change in redox potential over the pH range of 3.3-12.8. Magnetic susceptibility studies in solution give magnetic moments of 0.91-1.3 cm³ K mol^-1 (μ_eff value = 2.7-3.2) for both complexes. Solid-state measurements show that the susceptibility is consistent with a S = 1/2 state over the temperature range of 0 to 300 K, with no crossover to a high-spin state under these conditions. The crystal structure of [Fe(Mim)](OTf)₃ shows a six-coordinate all-nitrogen bound Fe(III) in a distorted octahedral environment. Relativistic ab initio wave function and density functional theory (DFT) calculations on [Fe(Mim)]³⁺, some with spin orbit coupling, were used to predict the ground spin state. Relative energies of the doublet, quartet, and sextet spin states were consistent with the doublet S = 1/2 state being the lowest in energy and suggested that excited states with higher spin multiplicities are not thermally accessible. Calculations were consistent with the magnetic susceptibility determined in the solid state.