Developing the family of picolinate ligands for Mn 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: HDPAAA; phenyl: HDPAPhA; dodecyl: HDPAC12A; 4-hexylphenyl: HDPAC6PhA). The protonation constants of the hexadentate DPAAA and pentadentate DPAPhA ligands and the stability constants of their Mn complexes were determined using pH-potentiometry (25 °C, 0.15 M NaCl). The mono-hydrated [Mn(DPAAA)] complex (log K = 13.19(5)) was found to be considerably more stable than the bis-hydrated [Mn(DPAPhA)] analogue (log K = 9.55(1)). A detailed H and O 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 × 10 and 1.3 ± 0.4 × 10 M, respectively. The X-ray structure of the complex {K(HO)}{[Mn(DPAAA)(HO)]} shows that the Mn ion in [Mn(DPAAA)] is coordinated to the six donor atoms of the ligand, a coordinated water molecule completing the pentagonal bipyramidal coordination environment.