Membrane-Permeable Mn(III) Complexes for Molecular Magnetic Resonance Imaging of Intracellular Targets.
J Am Chem Soc
; 138(17): 5483-6, 2016 05 04.
Article
em En
| MEDLINE
| ID: mdl-27088782
ABSTRACT
Intracellular compartments make up roughly two-thirds of the body, but delivery of molecular imaging probes to these spaces can be challenging. This situation is particularly true for probes designed for detection by magnetic resonance imaging (MRI), a high-resolution but relatively insensitive modality. Most MRI contrast agents are polar and membrane impermeant, making it difficult to deliver them in sufficient quantities for measurement of intracellular analytes. Here we address this problem by introducing a new class of planar tetradentate Mn(III) chelates assembled from a 1,2-phenylenediamido (PDA) backbone. Mn(III)-PDA complexes display T1 relaxivity comparable to that of Gd(III)-based contrast agents and undergo spontaneous cytosolic localization via defined mechanisms. Probe variants incorporating enzyme-cleavable acetomethoxy ester groups are processed by intracellular esterases and accumulate in cells. Probes modified with ethyl esters preferentially label genetically modified cells that express a substrate-selective esterase. In each case, the contrast agents gives rise to robust T1-weighted MRI enhancements, providing precedents for the detection of intracellular targets by Mn(III)-PDA complexes. These compounds therefore constitute a platform from which to develop reagents for molecular MRI of diverse processes inside cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imageamento por Ressonância Magnética
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Permeabilidade da Membrana Celular
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Meios de Contraste
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Manganês
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article