A pentadentate member of the picolinate family for Mn() complexation and an amphiphilic derivative

• Published in: Dalton transactions : an international journal of inorganic chemistry 2019-01, Vol.48 (2), p.696-71
• Main Authors: Pujales-Paradela, Rosa, Carniato, Fabio, Uzal-Varela, Rocío, Brandariz, Isabel, Iglesias, Emilia, Platas-Iglesias, Carlos, Botta, Mauro, Esteban-Gómez, David
• Format: Article
• Language: English
• Subjects: Aqueous solutions; Cartesian coordinates; Enthalpy; Hydrophobicity; Ligands; Magnetic induction; Magnetic relaxation; Mathematical analysis; Micelles; NMR; Nuclear magnetic resonance; Organic chemistry; Protonation; Recording; Serum albumin; Sodium chloride; Spectrophotometry; Water chemistry
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c8dt03856b

We report a pentadentate ligand containing a 2,2′-azanediyldiacetic acid moiety functionalized with a picolinate group at the nitrogen atom (H 3 paada), as well as a lipophylic derivative functionalized with a dodecyloxy group at position 4 of the pyridyl ring (H 3 C 12 Opaada). The protonation constants of the paada 3− ligand and the stability constant of the Mn( ii ) complex were determined using a combination of potentiometric and spectrophotometric titrations (25 °C, 0.15 M NaCl). A detailed relaxometric characterisation was accomplished by recording 1 H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles and 17 O chemical shifts and relaxation rates. These studies provide detailed information on the microscopic parameters that control their efficiency as relaxation agents in vitro . For the sake of completeness and to facilitate comparison, we also characterised the related [Mn(nta)] − complex (nta = nitrilotriacetate). Both the [Mn(paada)] − and [Mn(nta)] − complexes turned out to contain two inner-sphere water molecules in aqueous solution. The exchange rate of these coordinated water molecules was slower in [Mn(paada)] − ( k 298 ex = 90 × 10 7 s −1 ) than in [Mn(nta)] − ( k 298 ex = 280 × 10 7 s −1 ). The complexes were also characterised using both DFT (TPSSh/def2-TZVP) and ab initio CAS(5,5) calculations. The lipophylic [Mn(C 12 Opaada)] − complex forms micelles in solution characterised by a critical micellar concentration ( cmc ) of 0.31 ± 0.01 mM. This complex also forms a rather strong adduct with Bovine Serum Albumin (BSA) with an association constant of 5.5 × 10 4 M −1 at 25 °C. The enthalpy and entropy changes obtained for the formation of the adduct indicate that the binding event is driven by hydrophobic interactions. An amphiphilic Mn( ii ) complex presents improved relaxation properties thanks to micelle formation and binding to Bovine Serum Albumin.