Developing the family of picolinate ligands for Mn²⁺ complexation

We have reported here a series of ligands containing pentadentate 6,6′-(azanediylbis(methylene))dipicolinic acid units that differ in the substituent present at the amine nitrogen atom (acetate: H₃DPAAA; phenyl: H₂DPAPhA; dodecyl: H₂DPAC12A; 4-hexylphenyl: H₂DPAC6PhA). The protonation constants of the hexadentate DPAAA^3- and pentadentate DPAPhA^2- ligands and the stability constants of their Mn²⁺ complexes were determined using pH-potentiometry (25 °C, 0.15 M NaCl). The mono-hydrated [Mn(DPAAA)]^- complex (log K_MnL = 13.19(5)) was found to be considerably more stable than the bis-hydrated [Mn(DPAPhA)] analogue (log K_MnL = 9.55(1)). A detailed ¹H and ¹⁷O NMR relaxometric study was carried out to determine the parameters that govern the proton relaxivities of these complexes. The [Mn(DPAC12A)] complex, which contains a dodecyl lipophilic chain, forms micelles in solution characterized by a critical micellar concentration (cmc) of 96(9) μM. The lipophilic [Mn(DPAC6PhA)] and [Mn(DPAC12A)] derivatives form rather strong adducts with Human Serum Albumin (HSA) with association constants of 7.1 ± 0.1 × 10³ and 1.3 ± 0.4 × 10⁵ M^-1, respectively. The X-ray structure of the complex {K(H₂O)₄}{[Mn(DPAAA)(H₂O)]}₂ shows that the Mn²⁺ ion in [Mn(DPAAA)]^- is coordinated to the six donor atoms of the ligand, a coordinated water molecule completing the pentagonal bipyramidal coordination environment.