J Inorg Biochem. 2026 Sep 9;286:113454. doi: 10.1016/j.jinorgbio.2026.113454. Online ahead of print.

ABSTRACT

Responsive MRI probes are a powerful platform for the non-invasive detection of enzymatic activity in biological tissues. Herein, two series of DO3A-based molecular probes, LnL¹ and LnL² (Ln = Gd³⁺, Tb³⁺ and Tm³⁺), capable of responding to enzyme tyrosinase (TYR), were designed and evaluated. Ligands L^1-2 feature either an ester group (L¹) or a carboxylic group (L²) on their side arms. Luminescence lifetimes of the Tb³⁺ complexes in H₂O and D₂O revealed that both complexes have one water molecule in the inner-hydration sphere. UV-Vis studies revealed that both GdL¹ and GdL² undergo oxidative polymerization to form melanin-like polymers upon incubation with TYR, leading to a significant increase in longitudinal relaxivity. The Tm³⁺ complexes exhibited chemical exchange saturation transfer (CEST) effect. Although ¹H NMR results indicated that both complexes predominantly adopt the SAP configuration, the hydrophilic carboxylic group and hydrophobic ester group impart subtle structural variations. These structural modulations consequently underlie the marked differences observed in CEST effect and relaxivity behaviors upon enzyme catalysis, which paves the way to design desirable MRI agents via minor structural modification.

PMID:42748651 | DOI:10.1016/j.jinorgbio.2026.113454