Lanthanide Complexes Based on a 1,7-Diaza-12-crown-4 Platform Containing Picolinate Pendants: A New Structural Entry for the Design of Magnetic Resonance Imaging Contrast Agents

Abstract

We have synthesized a new macrocyclic ligand, N,N'-Bis[(6-carboxy-2-pyridyl)methyl]-1,7-diaza-12-crown-4 (H 2bp12c4), designed for complexation of lanthanide ions in aqueous solution. The X-ray crystal structure of the Gd (III) complex shows that the metal ion is directly bound to the eight donor atoms of the bp12c4 ligand, the ninth coordination site being occupied by an oxygen atom of a carboxylate group of a neighboring [Gd(bp12c4)] (+) unit, while the structure of the Lu (III) analogue shows the metal ion being only eight-coordinate. The hydration numbers obtained from luminescence lifetime measurements in aqueous solution of the Eu (III) and Tb (III) complexes suggest an equilibrium in aqueous solution between a dihydrated ( q = 2), ten-coordinate and a monohydrated ( q = 1), nine-coordinate species. This has been confirmed by a variable temperature UV-vis spectrophotometric study on the Eu (III) complex. The structure of the complexes in solution has been investigated by (1)H and (13)C NMR spectroscopy, as well as by theoretical calculations performed at the DFT (B3LYP) level. The results indicate that the change in hydration number occurring around the middle of the lanthanide series is accompanied by a change in the conformation adopted by the complexes in solution [Delta(lambdalambdalambdalambda) for q = 2 and Lambda(deltalambdadeltalambda) for q = 1]. The structure calculated for the Yb (III) complex (Lambda(deltalambdadeltalambda)) is in good agreement with the experimental structure in solution, as demonstrated by the analysis of the Yb (III)-induced paramagnetic (1)H shifts.

Kinetics Are Crucial When Targeting Copper Ions to Fight Alzheimer's Disease: An Illustration with Azamacrocyclic Ligands

“…Bisformyl-cyclam (1) [28] and methyl 6-(chloromethyl)picolinate (2) [29] were synthesized as previously described (see Scheme S1 in the Supporting Information). Bisformyl-cyclam (1) [28] and methyl 6-(chloromethyl)picolinate (2) [29] were synthesized as previously described (see Scheme S1 in the Supporting Information).…”

An Eighteen‐Membered Macrocyclic Ligand for Actinium‐225 Targeted Alpha Therapy

“…H 2 macropa was synthesized according to published procedures and characterized by conventional techniques, including X‐ray crystallography (see Figure S1, and Tables S1 and S2 in the Supporting Information). Previous studies have shown that macropa, for which the thermodynamic affinity for the whole lanthanide series was evaluated, is selective for the larger metal ions La 3+ , Pb 2+ , and Am 3+ over the smaller Lu 3+ , Ca 2+ , and Cm 3+ ions .…”

An Eighteen‐Membered Macrocyclic Ligand for Actinium‐225 Targeted Alpha Therapy

“…[19] Furthermore,the 225 Ac-radiolabeling kinetics of this ligand are slow (see below), thus necessitating the application of heat if short labeling times are required. H 2 macropa was synthesized according to published procedures [23,24] and characterized by conventional techniques, including X-ray crystallography (see Figure S1, and Tables S1 and S2 in the Supporting Information). H 2 macropa was synthesized according to published procedures [23,24] and characterized by conventional techniques, including X-ray crystallography (see Figure S1, and Tables S1 and S2 in the Supporting Information).…”