Stable Europium(III) Complexes with Short Linkers for Site‐Specific Labeling of Biomolecules

In this study, two new terpyridine‐based Eu(III) complexes were synthesized, the structures of which were optimized for luminescence resonance energy‐transfer (LRET) experiments. The complexes showed high quantum yields (32 %); a single long lifetime (1.25 ms), which was not influenced by coupling to protein; very high stability in the presence of chelators such as ethylenediamine‐N,N,N′,N′‐tetraacetate and ethylene glycol‐bis(2‐aminoethylether)‐N,N,N′,N′‐tetraacetic acid; and no interaction with cofactors such as adenosine triphosphate and guanosine triphosphate. A special feature is the short length of the linker between the Eu(III) ion and the maleimide or hydrazide function, which allows for site‐specific coupling of cysteine mutants or unnatural keto amino acids. As a consequence, the new complexes appear particularly suited for accurate distance measurements in biomolecules by LRET.