A Bis(pyridine N-oxide) Analogue of DOTA: Relaxometric Properties of the Gd super(III) Complex and Efficient Sensitization of Visible and NIR-Emitting Lanthanide(III) Cations Including Pr super(III) and Ho super(III)

• Published in: Chemistry : a European journal 2014-11, Vol.20 (45), p.14834-14845
• Main Authors: Martins, Andre F, Eliseeva, Svetlana V, Carvalho, Henrique F, Teixeira, Joao MC, Paula, Carlos TB, Hermann, Petr, Platas-Iglesias, Carlos, Petoud, Stephane, Toth, Eva, Geraldes, Carlos FGC
• Format: Article
• Language: English
• Subjects: Analogue; Aqueous solutions; Emittance; Imaging; Ligands; Magnetic resonance imaging; Optical properties; Spectroscopy
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201403856

We report the synthesis of a cyclen-based ligand (4,10-bis[(1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododec a ne-1,7-diacetic acid=L1) containing two acetate and two 2-methylpyridine N-oxide arms anchored on the nitrogen atoms of the cyclen platform, which has been designed for stable complexation of lanthanide(III) ions in aqueous solution. Relaxometric studies suggest that the thermodynamic stability and kinetic inertness of the Gd super(III) complex may be sufficient for biological applications. A detailed structural study of the complexes by super(1)HNMR spectroscopy and DFT calculations indicates that they adopt an anti- Delta ( lambda lambda lambda lambda ) conformation in aqueous solution, that is, an anti-square antiprismatic (anti-SAP) isomeric form, as demonstrated by analysis of the super(1)HNMR paramagnetic shifts induced by Yb super(III). The water-exchange rate of the Gd super(III) complex is ${k{{298\hfill \atop {\rm ex}\hfill}}}$[Imageomitted] =6.710 super(6)s super(-1), about a quarter of that for the mono-oxidopyridine analogue, but still about 50% higher than the ${k{{298\hfill \atop {\rm ex}\hfill}}}$[Imageomitted] of GdDOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). The 2-methylpyridine N-oxide chromophores can be used to sensitize a wide range of Ln super(III) ions emitting in both the visible (Eu super(III) and Tb super(III)) and NIR (Pr super(III), Nd super(III), Ho super(III), Yb super(III)) spectral regions. The emission quantum yield determined for the Yb super(III) complex ( ${Q{{{\rm L}\hfill \atop {\rm Yb}\hfill}}}$[Imageomitted] =7.3(1)10 super(-3)) is among the highest ever reported for complexes of this metal ion in aqueous solution. The sensitization ability of the ligand, together with the spectroscopic and relaxometric properties of its complexes, constitute a useful step forward on the way to efficient dual probes for optical imaging (OI) and MRI. Dual probes: Stable Ln super(III) complexes of the new cyclen-based ligand (4,10-bis[(1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododec a ne-1,7-diacetic acid) adopt an anti-square antiprismatic conformation in solution (see figure). The pyridine N-oxide chromophores efficiently sensitize the luminescence of a wide range of Ln super(III) ions emitting in both the visible (Eu super(III), Tb super(III)) and NIR (Pr super(III), Nd super(III), Ho super(III), Yb super(III)) spectral regions. The relaxometric properties of the Gd super(III) comple