ABSTRACT
Disclosed here are a piperazine, a pyridine, and two carboxylate groups containing pentadentate ligand H2pmpa and its corresponding water-soluble Mn(II) complex (1). DFT-based structural optimization implied that the complex had pentagonal bipyramidal geometry where the axial positions were occupied by two water molecules, and the equatorial plane was constituted by the ligand ON3O donor set. Thus, a bis(aquated) disc-like Mn(II) complex has been synthesized. The complex showed higher stability compared with Mn(II)-EDTA complex [log KMnL = 14.29(3)] and showed a very high r1 relaxivity value of 5.88 mM-1 s-1 at 1.41 T, 25 °C, and pH = 7.4. The relaxivity value remained almost unaffected by the pH of the medium in the range of 6-10. Although the presence of 200 equiv of fluoride and bicarbonate anions did not affect the relaxivity value appreciably, an increase in the value was noticed in the presence of phosphate anion due to slow tumbling of the complex. Cell viability measurements, as well as phantom MR images using clinical MRI imager, consolidated the possible candidature of complex 1 as a positive contrast agent.
Subject(s)
Contrast Media/chemistry , Coordination Complexes/chemistry , Gadolinium/chemistry , Magnetic Resonance Imaging , Manganese/chemistry , Cell Survival/drug effects , Contrast Media/chemical synthesis , Contrast Media/pharmacology , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Dose-Response Relationship, Drug , Gadolinium/pharmacology , HeLa Cells , Humans , Hydrogen-Ion Concentration , Manganese/pharmacology , Molecular Structure , Quantum Theory , Structure-Activity RelationshipABSTRACT
To attain high relaxivity as well as stability, a new water-soluble, water-coordinated Gd(iii) complex, which was synthesised by reacting equimolar amounts of picolinate-based ligand H4peada and GdCl3·xH2O at pH â¼ 6.5, was examined. The number of inner sphere water molecules (q) in the complex was found to be 1.7 ± 0.1 from luminescence lifetime measurements of its Tb(iii) congener, complex 2. At 1.41 T, 25 °C, and pH = 7.4, the longitudinal relaxivity (r1) value of the complex was found to be 6.08 mM-1 s-1, which remained almost constant in the pH range 4-10. The r1 relaxivity value has not been affected in the presence of a 100 fold excess of bicarbonate and phosphate anions, whereas in the case of fluoride ions, the value dropped to 4.6 mM-1 s-1 due to a binding interaction of fluoride ions by replacing inner sphere water molecules of the complex. From the potentiometric titration method, the stability constant of the complex was found to be log KGdL = 17.0 ± 0.08 (in 0.15 M KCl and 25 °C). At pH = 7.4, the pGd value of ligand H4peada was found to be 14.01 which was comparable to the commercially available MRI contrast agent Omniscan®. Phantom MR images of the complex under a clinical MR scanner at 1.5 T also demonstrated the usefulness of complex 1 as a potential MRI contrast agent.
ABSTRACT
Ligand H4bedik was reacted with MnCl2·4H2O at pH â¼ 6.5 to give a highly water-soluble and water-coordinated Mn(ii) complex (). The complex was found to show r1 = 3.11 mM(-1) s(-1) per Mn(ii) at 1.4 T and 6.26 mM(-1) s(-1) per Mn(ii) at 14.1 T at 25 °C, pH = 7.4. In addition to r1, the r2 at 14.1 T was found to be 132.78 mM(-1) s(-1) per Mn(ii) at 25 °C, pH = 7.4.
