Inner- and Second-Sphere Interactions of Co(II) and Fe(II) Parashift Agents with Lactate, Trifluorolactate, and Fluoride

Three pentadentate ligands based on 1,4,7-triazacyclononane (TACN) bearing 6-methyl-2-picolyl pendants and ancillary groups alkyl-sulfonate (L1), benzyl (L2), or proton (L3) were prepared to generate Fe(II) and Co(II) complexes as paramagnetic shift (parashift) agents with available coordination sites for anion binding. The solid-state structure of [Co(L2)(NO₃)](NO₃) confirms a six-coordinate complex cation with distorted octahedral geometry. ¹⁷O NMR spectroscopy studies support rapidly exchanging inner-sphere water for [Co(L1)]⁺, [Co(L2)]²⁺, and [Co(L3)]²⁺ at neutral pH and for [Fe(L1)]⁺ and [Fe(L2)]²⁺ under mildly acidic conditions. The methyl proton resonances of [Co(L1)]⁺ and [Co(L2)]²⁺ appear at −45 ppm and +40 ppm and those of [Co(L3)]²⁺ appear at −51 ppm and +21 ppm, compared to those of the symmetrical complex [Co(L4)]²⁺ at 8 ppm. [Fe(L1)]⁺ and [Fe(L2)]²⁺ have methyl proton resonances at −38 or −39 ppm, which compare to that of [Fe(L4)]²⁺ at 21 ppm. ¹H and ¹⁹F NMR spectroscopy studies suggest fluoride binds as an inner-sphere ligand to Fe(II) complexes and to [Co(L1)]⁺ and [Co(L2)]²⁺. Co(II) and Fe(II) complexes with bound water show second-sphere interactions with trifluorolactate and fluoride as supported by NMR studies. Magnetic resonance spectroscopy imaging at 7 T demonstrates strong, well-resolved methyl signals for [Co(L1)]⁺ and [Co(L2)]²⁺, highlighting their potential as parashift probes.