An overview of the design and development of highly luminescent Ln(III) complexes (with Ln = Tb, Eu) for applications in biotechnology will be presented. In particular, developments utilizing the 2-hydroxyisophthalamide (IAM) chelate for Tb(III).(1-3) These Tb(III) complexes exhibit highly efficient emission (Ftotal > 50%), large extinction coefficients (emax >20,000 M_1 cm_1), and long luminescence lifetimes (tH2O> 2.45 ms) at dilute concentrations in standard biological buffers.The Tb(III) complexes thus formed display long-term stability, with little if any change in their spectral properties (including lifetime, quantum yield, and emission spectrum) over time or in different chemical environments. Functionalized derivatives with terminal amine, carboxylate, and N-hydroxysuccinimide groups suitable for derivatization and protein bioconjugation have also been developed. These bifunctional ligands have been covalently attached to a number of different proteins, and the terbium complexes' exceptional photophysical properties are retained. These compounds establish a new aqueous stability and quantum yield standard for long-lifetime lanthanide reporters. They are now in commercial agents for use in Homogeneous Time Resolved Fluorescence (HTRF) technology. Such assays have become widespread in pharmacology and biotechnology. By using the long-lived luminescence of a lanthanide energy donor, the sensitivity of this assay format can be vastly improved by using time gated excitation and detection. These compounds are now used in commercial products by three different companies.(4)(1) S. Petoud, S.M. Cohen, J.-C.G. B�nzli, K.N. Raymond, JACS, 2003  , 125, 13324-13325.(2) A.P.S. Samuel, E.G. Moore, M. Melchior, J. Xu, K.N. Raymond, Inorg. Chem., 2008  , 47, 7535-7544.(3) J. Xu, T.M. Corneillie, E.G. Moore, G.-L. Law, N.G. Butlin, K.N. Raymond, J. Am. Chem. Soc. 2011,  133,19900�19910.(4) http://www.lumiphore.com

Lanthanide time resolved luminescence: From basics to business

247th National Meeting (2014)

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