Molecular Engineering of Self-Immolative Bioresponsive MR Probes

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Apr 28

PMID 37116079

Authors

Jian-Hong Tang

Hao Li

Chaonan Yuan

Giacomo Parigi

Claudio Luchinat

Thomas J Meade

Affiliations

Soon will be listed here.

Abstract

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" ( = 1.8 mM s at 1.41 T). However, upon enzymatic processing, it generates a significantly higher relaxivity with a Δ = 106% versus Δ ∼ 20% reported previously. Single X-ray crystal and nuclear magnetic relaxation dispersion analyses offer mechanistic insights regarding MR signal enhancement at the molecular scale. This work demonstrates a pyridyl-carbamate-based self-immolative molecular platform for the construction of enzymatic bio-responsive MR agents, which can be adapted to a wide range of other targets for exploring stimuli-responsive materials and biomedical applications.

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