title: A bis(pyridine N-oxide) analogue of DOTA: relaxometric properties of the Gd(III) complex and efficient sensitization of visible and NIR-emitting lanthanide(III) cations including Pr(III) and Ho(III).
abstract: We report the synthesis of a cyclen-based ligand (4,10-bis[(1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-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(III) complex may be sufficient for biological applications. A detailed structural study of the complexes by (1) H NMR spectroscopy and DFT calculations indicates that they adopt an anti-Δ(λλλλ) conformation in aqueous solution, that is, an anti-square antiprismatic (anti-SAP) isomeric form, as demonstrated by analysis of the (1) H NMR paramagnetic shifts induced by Yb(III) . The water-exchange rate of the Gd(III) complex is ${k{{298\hfill \atop {\rm ex}\hfill}}}$=6.7×10(6)  s(-1) , about a quarter of that for the mono-oxidopyridine analogue, but still about 50 % higher than the ${k{{298\hfill \atop {\rm ex}\hfill}}}$ 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(III) ions emitting in both the visible (Eu(III) and Tb(III) ) and NIR (Pr(III) , Nd(III) , Ho(III) , Yb(III) ) spectral regions. The emission quantum yield determined for the Yb(III) complex (${Q{{{\rm L}\hfill \atop {\rm Yb}\hfill}}}$=7.3(1)×10(-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.
authors.affiliation: Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, P. O. Box 3046, 3001-401 Coimbra (Portugal); Coimbra Chemistry Center, Rua Larga, University of Coimbra, 3004-535 Coimbra (Portugal); Centre de Biophysique Moléculaire, CNRS, Rue Charles Sadron, 45071 Orléans (France).
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Eliseeva
authors.forename: Henrique F
authors.initials: HF
authors.lastname: Carvalho
authors.forename: João M C
authors.initials: JM
authors.lastname: Teixeira
authors.forename: Carlos T B
authors.initials: CT
authors.lastname: Paula
authors.forename: Petr
authors.initials: P
authors.lastname: Hermann
authors.forename: Carlos
authors.initials: C
authors.lastname: Platas-Iglesias
authors.forename: Stephane
authors.initials: S
authors.lastname: Petoud
authors.forename: Eva
authors.initials: E
authors.lastname: Tóth
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
keywords: MRI; cyclen ligands; imaging agents; lanthanides; luminescence