PAPER www.rsc.org/dalton | Dalton Transactions Relaxation and luminescence studies on hydrated bipyridyl- and terpyridyl-based lanthanide complexes† Vojtˇ ech Kub´ ıˇ cek, a Anna Hamplov´ a, a,b Laurence Marib´ e, c Samir Mameri, c Raymond Ziessel, c ´ Eva T´ oth* a and Lo¨ ıc Charbonni` ere* c,d Received 1st July 2009, Accepted 1st September 2009 First published as an Advance Article on the web 29th September 2009 DOI: 10.1039/b913084e The synthesis of the novel ligand L2, based on a 2,2¢-bipyridine functionalized by a carboxylate function and a methyleneiminodiacetate group in positions 6 and 6¢, is described. Its europium complex, [EuL2(H 2 O) 3 ], has been prepared and characterized. The spectroscopic properties of [EuL2(H 2 O) 3 ] were studied by means of absorption, and both steady-state and time-resolved luminescence spectroscopy. Although L2 displays a very good sensitization efficiency (h sens. = 89%), the overall luminescence quantum yield of the complex is rather poor (2.6%). This results from strong non-radiative deactivations due to the presence of three water molecules in the first coordination sphere, as evidenced by luminescence lifetime measurements in H 2 O and D 2 O. The relaxation properties of the Gd 3+ complexes obtained with ligands L2 and L1, the latter containing an additional pyridine ring in the aromatic core, were assessed by means of 17 O NMR and nuclear magnetic relaxation dispersion (NMRD). The calculated water exchange rates for both complexes are faster than those of currently used contrast agents (k ex 298 = 14.0 ± 1.5 ¥ 10 6 and 11.1 ± 1.1 ¥10 6 s -1 for [GdL1(H 2 O) 2 ] and [GdL2(H 2 O) 3 ], respectively). The rotational correlation time calculated for [GdL1(H 2 O) 2 ] appeared to be long (110 ± 16 ps vs 65 ± 5ps for [GdL2(H 2 O) 3 ]), pointing to a hindered rotation due to the larger aromatic frame. Finally, the interaction of the two Gd complexes with hydrogencarbonate and phosphate anions was studied by relaxivity measurements, showing that both anions are able to compete with water molecules as ligands for Gd 3+ , with HCO 3 - showing a better affinity. Introduction In the last decades, the successful use of lanthanide(III) chelates in various biomedical fields has promoted a considerable in- terest in their coordination chemistry. 1 Gd 3+ complexes, used in clinics to enhance image contrast in magnetic resonance imaging, certainly represent the most widespread application. 2 Luminescent lanthanide chelates are also gaining importance in labeling experiments in time-resolved fluoroimmunoassays, 3 luminescent resonant energy transfer, 4 or time-resolved lumines- cence microscopy (TRLM). 5 Nowadays, much effort is directed towards coupling different bioimaging modalities, with the benefit of simultaneously taking advantage of the positive features of each technique. Magnetic resonance imaging provides excellent spatial and temporal resolution without depth limitation, but, it has low sensitivity, while optical imaging offers great sensitivity a Centre de Biophysique Mol´ eculaire, CNRS, rue Charles Sadron, 45071, Orl´ eans, France. E-mail: eva.jakabtoth@cnrs-orleans.fr; Fax: +33 (0)2 3863 1517; Tel: +33 (0)2 3825 7625 b Department of Analytical Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, Prague 2, 128 40, Czech Republic c Laboratoire de Chimie Organique et Spectroscopie Avanc´ ee, UMR 7515 associ´ ee au CNRS, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France d Laboratoire d’Ing´ enierie Mol´ eculaire Analytique, IPHC, UMR 7178, ECPM, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France. E-mail: l.charbonn@chimie.u-strasbg.fr † Electronic supplementary information (ESI) available: Equations used in the analysis of 17 O NMR and NMRD data; relaxometric titration curves in the presence of anions. See DOI: 10.1039/b913084e and resolution but low penetration into tissue. Luminescent–MRI bimodal imaging could combine the high sensitivity of the optical method with the high resolution of MRI. 6 So far, the majority of imaging probes used in bimodal MR and optical imaging have been fluorescent dyes conjugated to either iron oxide nanoparticles or to macromolecular Gd 3+ complexes. However, the idea of creating bimodal agents based on an identical metal chelator for complexation to Gd 3+ and a luminescent lanthanide ion is rather appealing. The chemical similarities over the entire lanthanide series make it easy to substitute one lanthanide ion with another without greatly affecting the complex stability. Nevertheless, lanthanide-based bimodal agents represent an important challenge for the coordination chemist. The presence of at least one hydration water molecule in the inner coordination sphere of the Gd 3+ ion is a prerequisite for MRI applications. However, such metal-coordinated water molecules are detrimental for the luminescence of the lanthanides, since they induce quenching via non-radiative deactivation pathways. 7 Nevertheless, recent reports have evidenced that it is possible to overcome the quenching effect of the coordinated water molecules by applying ligands that are very good sensitizers of lanthanide luminescence. 8 Even complexes with two inner sphere water molecules have been shown to display interesting luminescence properties, including in the near infra-red region. 9 The MRI efficacy of a Gd 3+ complex is expressed by its proton relaxivity, which is defined as the paramagnetic enhancement of the longitudinal water proton relaxation rate referred to one millimolar concentration of the agent. The relaxivity is directly 9466 | Dalton Trans., 2009, 9466–9474 This journal is © The Royal Society of Chemistry 2009