biostudies-literatureTang JHNational Institute of Neurological Disorders and StrokeNCI NIH HHSNINDS NIH HHS10045-10050https://www.ebi.ac.uk/biostudies/studies/S-EPMC10769484biostudies-literatureUnknown145(18)Real-time detection of bio-event in whole animals provides essential information for understanding biological and therapeutic processes. Magnetic resonance (MR) imaging represents a non-invasive approach to generating three-dimensional anatomic images with high spatial-temporal resolution and unlimited depth penetration. We have developed several self-immolative enzyme-activatable agents that provide excellent in vivo contrast and function as gene expression reporters. Here, we describe a vast improvement in image contrast over our previous generations of these bioresponsive agents based on a new pyridyl-carbamate Gd(III) complex. The pyridyl-carbamate-based agent has a very low MR relaxivity in the "off-state" (<i>r</i>₁ = 1.8 mM^-1 s^-1 at 1.41 T). However,Journal of the American Chemical SocietyMolecular Engineering of Self-Immolative Bioresponsive MR Probes.PMC10769484R01 NS115571P30 CA0605535R01NS115571Luchinat CLi HYuan CTang JHMeade TJParigi GfalseMolecular Engineering of Self-Immolative Bioresponsive MR Probes.Real-time detection of bio-event in whole animals provides essential information for understanding biological and therapeutic processes. Magnetic resonance (MR) imaging represents a non-invasive approach to generating three-dimensional anatomic images with high spatial-temporal resolution and unlimited depth penetration. We have developed several self-immolative enzyme-activatable agents that provide excellent in vivo contrast and function as gene expression reporters. Here, we describe a vast improvement in image contrast over our previous generations of these bioresponsive agents based on a new pyridyl-carbamate Gd(III) complex. The pyridyl-carbamate-based agent has a very low MR relaxivity in the "off-state" (<i>r</i>₁ = 1.8 mM^-1 s^-1 at 1.41 T). However,2023-01-01T00:00:00Z2023 May2026-06-02T01:39:03.648Z2025-02-19T03:18:02.375ZS-EPMC107694843711607910.1021/jacs.2c13672