Divergent Approach to a Large Variety of Versatile Luminescent Lanthanide Complexes Pascal Kadjane, † Matthieu Starck, † Franck Camerel, † Diana Hill, ‡ Niko Hildebrandt, § Raymond Ziessel,* ,† and Lo :: ıc J. Charbonni  ere* ,†,^ † Laboratoire de Chimie Organique et Spectroscopies Avanc ees, UMR 7515 associ  ee au CNRS, ECPM, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France, ‡ Institut f :: ur Chemie, Physikalische Chemie, Universit :: at Potsdam, Karl-Liebknecht-Strasse 24-25, 14476 Potsdam-Golm, Germany, § Fraunhofer Institute for Applied Polymer Research, NanoPolyPhotonics, Wissenschaftspark Golm, Geiselbergstrasse 69, 14476 Postdam-Golm, Germany, and ^ Laboratoire d’Ing enierie Mol  eculaire Analytique, UMR 7178 CNRS, IPHC, ECPM, 25 rue Becquerel, 67087 Strasbourg Cedex 02, France Received January 20, 2009 Using a regioselective strategy for nucleophilic aromatic substitu- tion on polyfluoropyridines, a nonacoordinating precursor was designed that is adequately suited for complexation of lanthanide cations. Further functionalizations afforded numerous applications for near-IR emission, two-photon absorption spectroscopy, or the formation of luminescent gels. Luminescent lanthanide complexes and labels offer nu- merous advantages over fluorescent organic compounds or other luminescent coordination complexes. 1 They display linelike emission bands, large Stokes shifts, and generally very long luminescence lifetimes and emit over the visible and near-IR (NIR) domains, depending on the lanthanide used. While still in their infancy in luminescence microscopy with one- 2 or two-photon excitation, 3 they have undoubtedly reached the level of standards in fluoroimmunoassays, easily reaching subpicomolar detection limits. 4 For this class of complexes, a bright luminescence can only be achieved by taking advantage of the antenna effect, 5 allowing for indirect population of the lanthanide-centered excited states through ligand excitation. The choice of the ligand acting as an antenna must be guided by the matching of the intermediate ligand-centered excited states with that of the targeted emitting lanthanide cation. This generally re- quires synthesis of the proper ligand for each specific lantha- nide. Furthermore, efficient luminescence can only be obtained by optimal protection of the cation from solvent molecules including water. Coordination of the latter in the first sphere of the lanthanide leads to detrimental nonradia- tive processes 6 that drastically quench the luminescence, in particular for NIR emitters. Finally, a targeted use of luminescent lanthanide complexes will also require the syn- thetic input of a specific function to integrate the complex into a functional molecular device, e.g., a grafting function, for labeling applications, 4,7 or a recognition site, for sensing and detection. 8 Up to now, fulfillment of all of these require- ments is achieved by a specific synthetic design of the ligand fitted to the selected lanthanide cation. We here propose an alternative synthetic approach in which the ligand design offers diverging pathways providing first an efficient complexation site, which can then be func- tionalized at will to tune the required electronic properties and/or to introduce specific functions. Using this new meth- odology, a broad scope of highly luminescent lanthanide complexes with visible and NIR emission can be obtained for various applications. The synthesis of the complexation pocket relies on the largely underexploited nucleophilic aromatic substitution reaction of polyfluoropyridine derivatives (Scheme 1). Following the pioneering work of Schlosser an co-work- ers, 9 it was possible to take advantage of the higher reactivity of the para-fluorinated position in 2,4,6-trifluoropyridine to introduce a hydrazine function, which is further transformed into 1 using dibromide in chloroform. 10 This key intermedi- ate allows one to direct the nucleophilic substitution reactions toward the 2 and 6 positions, with the bromine function being *To whom correspondence should be addressed. E-mail: ziessel@ chimie.u-strasbg.fr (R.Z.), charbonn@chimie.u-strasbg.fr (L.J.C.). (1) B :: unzli, J.-C. G.; Piguet, C. Chem. Rev. 2005, 34, 1048. (2) Pandya, S.; Yu, J.; Parker, D. Dalton Trans. 2006, 2757. (3) Picot, A.; D’Al eo, A.; Baldeck, P. L.; Grichine, A.; Duperray, A.; Andraud, C.; Maury, O. J. Am. Chem. Soc. 2008, 130, 1532. (4) (a) Hildebrandt, N.; Charbonni ere, L.; Beck, M.; Ziessel, R.; L :: ohmannsr :: oben, H.-G. Angew. Chem., Int. Ed. 2005, 44, 7612. (b) Hildeb- randt, N.; Charbonni ere, L. J.; L :: ohmannsr :: oben, H.-G. J. Biomed. Biotechnol. 2007, Article ID 79169, 6 pages. (5) Weissmann, S. I. J. Chem. Phys. 1942, 10, 214. (6) (a) Supkowski, R. M.; Horrocks, W. D. W.Jr. Inorg. Chim. Acta 2002, 340, 44. (b) Beeby, A.; Clarkson, I. M.; Dickins, R. S.; Faulkner, S.; Parker, D.; Royle, L.; de Sousa, A. S.; Williams, J. A. G.; Woods, M. J. Chem. Soc., Perkin Trans. 2 1999, 493. (7) Yuan, J.; Wang, V. TrAC, Trends Anal. Chem. 2006, 25, 490. (8) (a) Song, B.; Wang, G. L.; Tan, M. Q.; Yuan, J. L. J. Am. Chem. Soc. 2006, 128, 13442. (b) Charbonni ere, L.; Hildebrandt, N. Eur. J. Inorg. Chem. 2008, 3241. (9) (a) Schlosser, M.; Bobbio, C.; Rausis, T. J. Org. Chem. 2005, 70, 2494. (b) Schlosser, M.; Rausis, T.; Bobbio, C. Org. Lett. 2005, 7, 127. (10) Cefalo, D. R.; Henderson, J. I.; Mokri, H. H. U.S. Patent 7,087,755, 2006. Inorg. Chem. 2009, 48, 4601–4603 4601 DOI:10.1021/ic9001169 © 2009 American Chemical Society Published on Web 4/15/2009 pubs.acs.org/IC