Rigid Bispyclen Ligand Appended with Two Malonate Groups: Fast, Highly Stable, and Inert Gd(III) Complexation
Abstract
In the aim of designing novel chelators for stable and inert Gd(III) complexation, we report the synthesis of the H4BPDMA ligand which combines a rigidified bispyclen macrocycle platform with two malonate pendants, and an in-depth equilibrium, kinetic relaxation, and structural investigation of its Gd(III) complex. Despite its rigid macrocyclic nature, H4BPDMA is capable of very rapid complex formation with Gd(III) even in acidic conditions. The [Gd(BPDMA)]− possesses high thermodynamic stability, and most remarkably, a conditional stability comparable to that of [Gd(DOTA)]− (pGd = 15.6 and 16.2, respectively; cGdL = 10–5 M, pH 7.4). Cu-transmetalation studies show that [Gd(BPDMA)]− dissociation occurs via proton-assisted pathways with a dissociation half-life of 3.2 years (37 °C, pH 7.4). DFT calculations predict a nine-coordinate [Gd(BPDMA)]− complex, involving coordination of one water molecule and eight ligand donor atoms, in accordance with 13C NMR data collected on the corresponding Eu(III) and Yb(III) complexes. Luminescence lifetime measurements on the Eu(III) analogue support monohydration in solution. The water proton relaxation enhancement effect of [Gd(BPDMA)]− (r1 = 4.6 mM–1s–1, 25 °C, 20 MHz) is similar to that of clinical MRI contrast agents, and 17O NMR data confirm relatively fast water exchange (kex298 = (43 ± 8) × 106 s–1).
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BibTeX
@article{bunda2026rigid,
title = {{Rigid Bispyclen Ligand Appended with Two Malonate Groups: Fast, Highly Stable, and Inert Gd(III) Complexation}},
author = {Szilvia Bunda and Norbert Lihi and Abraham Estifanos Debretsion and Simon Héry and Hervé Meudal and Éva Tóth and Ferenc Krisztián Kálmán},
journal = {Inorganic Chemistry},
year = {2026},
month = jul,
doi = {10.1021/acs.inorgchem.6c03109},
url = {https://hal.science/hal-05843457v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Rigid Bispyclen Ligand Appended with Two Malonate Groups: Fast, Highly Stable, and Inert Gd(III) Complexation
AU - Szilvia Bunda
AU - Norbert Lihi
AU - Abraham Estifanos Debretsion
AU - Simon Héry
AU - Hervé Meudal
AU - Éva Tóth
AU - Ferenc Krisztián Kálmán
PY - 2026
DA - 2026/07/28
JO - Inorganic Chemistry
DO - 10.1021/acs.inorgchem.6c03109
UR - https://hal.science/hal-05843457v1
AB - In the aim of designing novel chelators for stable and inert Gd(III) complexation, we report the synthesis of the H4BPDMA ligand which combines a rigidified bispyclen macrocycle platform with two malonate pendants, and an in-depth equilibrium, kinetic relaxation, and structural investigation of its Gd(III) complex. Despite its rigid macrocyclic nature, H4BPDMA is capable of very rapid complex formation with Gd(III) even in acidic conditions. The [Gd(BPDMA)]− possesses high thermodynamic stability, and most remarkably, a conditional stability comparable to that of [Gd(DOTA)]− (pGd = 15.6 and 16.2, respectively; cGdL = 10–5 M, pH 7.4). Cu-transmetalation studies show that [Gd(BPDMA)]− dissociation occurs via proton-assisted pathways with a dissociation half-life of 3.2 years (37 °C, pH 7.4). DFT calculations predict a nine-coordinate [Gd(BPDMA)]− complex, involving coordination of one water molecule and eight ligand donor atoms, in accordance with 13C NMR data collected on the corresponding Eu(III) and Yb(III) complexes. Luminescence lifetime measurements on the Eu(III) analogue support monohydration in solution. The water proton relaxation enhancement effect of [Gd(BPDMA)]− (r1 = 4.6 mM–1s–1, 25 °C, 20 MHz) is similar to that of clinical MRI contrast agents, and 17O NMR data confirm relatively fast water exchange (kex298 = (43 ± 8) × 106 s–1).
SN - 0020-1669
SN - 1520-510X
ER -