Characterization of the Fe(III)-Tiron System in Solution through an Integrated Approach Combining NMR Relaxometric, Thermodynamic, Kinetic, and Computational Data

[Image: see text] The Fe(III)-Tiron system (Tiron = 4,5-dihydroxy-1,3-benzenedisulfonate) was investigated using a combination of (1)H and (17)O NMR relaxometric studies at variable field and temperature and theoretical calculations at the DFT and NEVPT2 levels. These studies require a detailed knowledge of the speciation in aqueous solution at different pH values. This was achieved using potentiometric and spectrophotometric titrations, which afforded the thermodynamic equilibrium constants characterizing the Fe(III)-Tiron system. A careful control of the pH of the solution and the metal-to-ligand stoichiometric ratio allowed the relaxometric characterization of [Fe(Tiron)(3)](9–), [Fe(Tiron)(2)(H(2)O)(2)](5–), and [Fe(Tiron)(H(2)O)(4)](−) complexes. The (1)H nuclear magnetic relaxation dispersion (NMRD) profiles of [Fe(Tiron)(3)](9–) and [Fe(Tiron)(2)(H(2)O)(2)](5–) complexes evidence a significant second-sphere contribution to relaxivity. A complementary (17)O NMR study provided access to the exchange rates of the coordinated water molecules in [Fe(Tiron)(2)(H(2)O)(2)](5–) and [Fe(Tiron)(H(2)O)(4)](−) complexes. Analyses of the NMRD profiles and NEVPT2 calculations indicate that electronic relaxation is significantly affected by the geometry of the Fe(3+) coordination environment. Dissociation kinetic studies indicated that the [Fe(Tiron)(3)](9–) complex is relatively inert due to the slow release of one of the Tiron ligands, while the [Fe(Tiron)(2)(H(2)O)(2)](5–) complex is considerably more labile.