Work

Exploring Bioinspired Ln3+ Complexes for Cu2+ Detection: Design and Efficacy as MRI Contrast Agents

Year: 2025

Type: article

Abstract: Imaging extracellular Cu2+ in vivo is important due to its role in physiological and pathological processes. Magnetic resonance imaging is a promising modality for this purpose but developing contrast agents selective for Cu2+ over abundant Zn2+ ions remains a challenge. We synthesized and characterized two novel ligands, DO3A‐picG and DO3A‐picGH, containing a macrocycle and a pendant arm for Cu2+ complexation inspired from the ATCUN site of human serum albumin. The corresponding Ln3+ complexes were studied in the presence and in the absence of Cu2+ through UV‐visible, fluorescence and EPR spectroscopies, as well as relaxivity measurements. These studies show that Gd‐DO3A‐picG and Gd‐DO3A‐picGH are non‐hydrated complexes, in which the pyridine‐amide moiety remains coordinated to Ln3+ even in the presence of Cu2+. While Gd‐DO3A‐picG does not respond to Cu2+, a sizeable relaxivity increase is observed for Gd‐DO3A‐picGH. This increase is attributed to an increased second‐sphere contribution to the relaxivity, i. e. a higher number of H2O molecules retained in close proximity to Gd3+ through H‐bonding. Finally, we show that Gd‐DO3A‐picGH binds Cu2+ with a μM affinity, and is selective for Cu2+ vs Zn2+.

Source: European Journal of Inorganic Chemistry

DOI: 10.1002/ejic.202500049