RESUMO
We have proposed recently that the DO3A-N-α-(amino)propionate chelator and its amide conjugates are leads to targeted, high relaxivity, safe contrast agents for magnetic resonance imaging. In this work we illustrate further the expeditious nature and robustness of the synthetic methodologies developed by preparing the DO3A-N-(α-pyrenebutanamido)propionate chelator. Its Gd(3+) chelate retains the optimized water exchange, high stability and inertness of the parent complex. The pyrene moiety imparts concentration-dependent self-assembly properties and aggregation-sensitive fluorescence emission to the Gd(3+) complex. The Gd(3+) complex displays pyrene-centred fluorescence whilst the Yb(3+) and Nd(3+) complexes exhibit sensitized lanthanide-centred near-infrared luminescence. The aggregated form of the complex displays high relaxivity (32 mM(-1) s(-1), 20 MHz, 25 °C) thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. The relaxivity is however still limited by chelate flexibility. This report demonstrates that the DO3A-N-(α-amino)propionate chelator is a valuable platform for constructing high relaxivity CA using simple design principles and robust chemistries accessible to most chemistry labs.
Assuntos
Complexos de Coordenação/química , Elementos da Série dos Lantanídeos/química , Animais , Quelantes/síntese química , Quelantes/química , Meios de Contraste/síntese química , Meios de Contraste/química , Meios de Contraste/metabolismo , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Gadolínio/química , Humanos , Cinética , Ligação Proteica , Pirenos/química , Ratos , Ratos Wistar , Albumina Sérica/química , Albumina Sérica/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Temperatura , Distribuição Tecidual , Água/químicaRESUMO
Gold nanoparticles functionalized with Gd(3+) chelates displaying fast water exchange, superb pH stability and inertness towards transmetalation with Zn(2+) have been prepared and characterized as a new high relaxivity (29 mM(-1) s(-1), 30 MHz, 25 °C) contrast agent potentially safe for in vivo MRI applications. The Lipari-Szabo treatment for internal rotation was used to evaluate the effect of linker flexibility on the relaxivity of the gold nanoparticles. The effect of fast water exchange on the relaxivity of gold nanoparticles functionalized with Gd(3+) chelates is also addressed in this communication.