Gadolinium Complex with Tris-Hydroxypyridinone as an Input for New Imaging Probes: Thermodynamic Stability, Molecular Modeling and Biodistribution
Year: 2025
Type: article
Abstract: The development of gadolinium-based magnetic resonance imaging (MRI) contrast agents (CAs) is a highly challenging and demanding research field in metal-coordination medicinal chemistry. The recognized high capacity of hydroxypyridinone (HOPO)-based compounds to coordinate Gd(III) led us to evaluate a set of physic-chemical-biological properties of a new Gd(III)-complex with an hexadentate tripodal ligand (H3L), containing three 3,4-HOPO chelating moieties attached to an anchoring cyclohexane backbone. In particular, the thermodynamic stability constants of the complex were evaluated by potentiometry, showing the formation of a high stable (1:1) Gd-L complex (log GdL = 26.59), with full coordination even in acid-neutral pH conditions. Molecular simulations of the Gd(III) complex revealed a minimum energy structure with somehow distorted octahedral geometry, involving full metal hexa-coordination by the three bidentate moieties of the ligand arms, indicating that extra water molecules should be coordinated to the metal ion, an important feature for the CAs (required enhancement of water proton relaxivity). In vivo biodistribution studies with the 67Ga complex, as surrogate of the corresponding Gd complex, showed in vivo stability and rapid excretion from the animal body. Though deserving further investigation, these results may give an input on future perspectives towards new MRI diagnostic agents.
Source: Molecules
Authors: Inês Dias, Lurdes Gano, Sílvia Chaves, Maria Amélia Santos
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W4408407141