Toward inert paramagnetic Ni(ii)-based chemical exchange saturation transfer MRI agents

Abstract

The Ni 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 and chxdedpa). The X-ray structure of the [Ni(dedpam)] complex reveals a six-coordinated metal ion with a distorted octahedral environment. The protonation constants of the dedpa and dedpam ligands and the stability constants of their Ni complexes were determined using pH-potentiometry and spectrophotometric titrations (25 °C, 0.15 M NaCl). The [Ni(dedpa)] complex (log K = 20.88(1)) was found to be considerably more stable than the corresponding amide derivative [Ni(dedpam)] (log K = 14.29(2)). However, the amide derivative [Ni(chxdedpam)] was found to be considerably more inert with respect to proton-assisted dissociation than the carboxylate derivative [Ni(chxdedpa)]. A detailed H NMR and DFT study was conducted to assign theH NMR spectra of the [Ni(chxdedpa)] and [Ni(chxdedpam)] complexes. The observed H NMR paramagnetic shifts were found to be dominated by the Fermi contact contribution. The amide resonances of [Ni(chxdedpam)] 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.

Mn2+ Complexes Containing Sulfonamide Groups with pH-Responsive Relaxivity

“…The procedures used for electrode calibration were described in detail elsewhere. 56 The formation of the Mn 2+ complexes of DPASAm 3− and NO2ASAm 3− was fast. In the case of the NOTA 3− complex, the equilibrium was attained more slowly, taking 5−10 min, depending on the pH.…”

“…A Crison micropH 2000 pH meter, connected to a glass electrode (Radiometer pHG211) and a reference electrode (Radiometer REF201), was used to measure the electromotive force (emf) values. The procedures used for electrode calibration were described in detail elsewhere . The formation of the Mn 2+ complexes of DPASAm 3– and NO2ASAm 3– was fast.…”

Applications for Transition-Metal Chemistry in Contrast-Enhanced Magnetic Resonance Imaging

“…143−153 The chemical shift in part per million and k ex values of transition-metal paraCEST agents are Table 6. Chemical Shift (ppm) and k ex for CEST Active Protons of X-ray Contrast Agents and Lanthanide-Based and Transition-Metal-Based paraCEST Agents Shown in Figure 10 functional group δ H (ppm) k ex (s −1 ) iopamidol 139 amide NH 4.10 2560 a iomeprol 154 amide NH 4.30 1830 a iohexol 154 amide NH 4.30 1610 a ioversol 154 amide NH 4.30 1630 a iodixanol 154 amide NH 4.30 1210 a Tb-DOTA-4AmCE 137 water coligand −600 32300 Dy-DOTA-4AmCE 137 water coligand −720 58800 Yb-HPDO3A 155 alcohol OH 71, b 99 b N/D Tm-DOTAM-Gly 156 amide NH −51 c 3450 Ho-DOTAM-Gly 156 amide NH 39 c 2500 Dy-DOTAM-Gly 156 amide NH 77 c 2500 Eu-DOTAM-EB 157 amide NH 53 12300 Fe-TCMT 158 amide NH 69 240 Fe-AMPT 158 aminopyridine NH 2 6.5 N/D Fe-BZT 158 benzothiazole −NH 53 N/D Fe-STHP 158 alcohol OH 54 3,000 Fe-DOTAM 158 amide NH 50 400 Fe-TAPC 147 aminopyridine NH 2 −79 1700 d Fe-NOPE 149 amide NH 92, 24 e 500 Co-TCMT 158 amide NH 32 890 Co-DOTAM 158 amide NH 45 300 Co-CCRM 158 amide NH 112 510 Co-TPT 158 pyrazole NH 135 9200 Co-HINO 143 imidazole NH 32 1020 a Co-TAPC 147 aminopyridine NH 2 −118 N/D Co-NOPE 149 amide NH 59, −19 e 240 Co-L5 152 alcohol OH 140 5000 f Ni-TCMT 158 amide NH 76 364 Ni-CCRM 158 amide NH 72 328 Ni-HINO 143 imidazole NH 55 1020 a Ni-NOPE 149 amide NH 72, 11 e 240 Ni-DOTAM 159 amide NH 73 330 Ni-chxdedpam 160 amide NH 91.5 e,g 6100 Cu ...…”

Recognition of AMP, ADP and ATP through Cooperative Binding by Cu(II) and Zn(II) Complexes Containing Urea and/or Phenylboronic—Acid Moieties

“…Thus, we used p A values defined as p A = −log[Anion] free using an anion concentration of 0.001 M and a concentration of [CuL n ] 2+ complex of 0.01 M (pH 7.0). The definition of p A is similar to that of p M often used to assess the relative stabilities of metal complexes in aqueous media [ 74 ]. The p A values obtained for all of the monophosphate anions are rather similar ( Figure 5 , see also Table 3 ), with no particular selectivity for any of them being observed.…”