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

Abstract

Two macrocyclic complexes of 1,4,7-triazacyclononane (TACN), one with N-methyl imidazole pendants, [Fe(Mim)], and one with unsubstituted NH imidazole pendants, [Fe(Tim)], were prepared with a view toward biomedical imaging applications. These low-spin Fe complexes produce moderately paramagnetically shifted and relatively sharp H NMR resonances for paraSHIFT and paraCEST applications. The [Fe(Tim)] 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)] produces a complex that dissociates more readily at high pH in comparison to [Fe(Tim)], which contains ionizable donor groups. Cyclic voltammetry studies show that the redox potential of [Fe(Mim)] is invariant with pH ( E = 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 cm K mol (μ 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) 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)], 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.

Probing the Local Magnetic Structure of the [FeIII(Tp)(CN)3]− Building Block Via Solid‐State NMR Spectroscopy, Polarized Neutron Diffraction, and First‐Principle Calculations

“…The choice of the active space, namely CAS(9,12), was driven by the previous ab‐initio study performed on the compound of interest and by the results of previous ab‐initio studies performed on related complexes with various transition metals . This active space corresponds to the five electrons of the Fe 3+ ion distributed in the five 3d orbitals, augmented by five unoccupied 3d′ orbitals to properly take into account the double‐shell effect.…”

Synthesis, Characterization, Modeling, and Antimicrobial Activity of FeIII, CoII, NiII, CuII, and ZnII Complexes Based on Tri‐substituted Imidazole Ligand

“…Due to the open‐shell nature of the metal complexes, unrestricted open‐shell method was used. In addition, doublet‐spin ground state was calculated for FeL, CoL, and CuL complexes, which was found to be more stable than quartet or higher states, whereas singlet state calculation was performed for the diamagnetic NiL and ZnL complexes. Hartree–Fock (HF) calculations were also performed for comparison with the DFT, where same basis set and spin multiplicity had been used.…”

The First-Row Transition Metals in the Periodic Table of Medicine

“…Recently, other applications and diseases have been investigated for treatment with Fe-based compounds. For example, Fe(II) and Fe(III) complexes are of interest as MRI contrast agents [119][120][121]. These complexes are alternative agents to the current standard agents that contain the lanthanide metal gadolinium, and provides options in cases when the MRI patient cannot clear the imaging agent, such as patients with kidney disorders [120].…”