Toward inert paramagnetic Ni(ii)-based chemical exchange saturation transfer MRI agents. Issue 43 (25th October 2017)

• Record Type: Journal Article
• Authors: Caneda-Martínez, Laura; Valencia, Laura; Fernández-Pérez, Isabel; Regueiro-Figueroa, Martín; Angelovski, Goran; Brandariz, Isabel; Esteban-Gómez, David; Platas-Iglesias, Carlos
• Is Part Of: Dalton transactions. Volume 46:Issue 43(2017)
• Page Start: 15095
• Page End: 15106
• Publication Date: 2017-10-25
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c7dt02758c
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Rigid Ni(ii ) complexes containing picolinamide groups show potential as MRI contrast agents operating through the chemical exchange saturation transfer mechanism. Abstract : The Ni 2+ complexes with hexadentate ligands containing two 6-methylpicolinamide groups linked by ethane-1, 2-diamine (dedpam) or cyclohexane-1, 2-diamine (chxdedpam) spacers were investigated as potential contrast agents in magnetic resonance imaging (MRI). The properties of the complexes were compared to that of the analogues containing 6-methylpicolinate units (dedpa 2− and chxdedpa 2− ). The X-ray structure of the [Ni(dedpam)] 2+ complex reveals a six-coordinated metal ion with a distorted octahedral environment. The protonation constants of the dedpa 2− and dedpam ligands and the stability constants of their Ni 2+ complexes were determined using pH-potentiometry and spectrophotometric titrations (25 °C, 0.15 M NaCl). The [Ni(dedpa)] complex (log K NiL = 20.88(1)) was found to be considerably more stable than the corresponding amide derivative [Ni(dedpam)] 2+ (log K NiL = 14.29(2)). However, the amide derivative [Ni(chxdedpam)] 2+ was found to be considerably more inert with respect to proton-assisted dissociation than the carboxylate derivative [Ni(chxdedpa)]. A detailed 1 H NMR and DFT study was conducted to assign the 1 H NMR spectra of the [Ni(chxdedpa)] and [Ni(chxdedpam)] 2+ complexes. The observed 1 H NMR paramagnetic shifts were found to be dominated by the Fermi contact contribution. The amide resonances of [Ni(chxdedpam)] 2+ at 91.5 and 22.2 ppm were found to provide a sizeable chemical exchange saturation transfer effect, paving the way for the development of NiCEST agents based on these rigid non-macrocyclic platforms.