Design and synthesis of site directed maleimide bifunctional chelators for technetium and rhenium

Sangeeta Ray Banerjee, Paul Schaffer, John W. Babich, John F. Valliant, Jon Zubieta

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

A new family of heterobifunctional linkers (L1-L9) containing a terminus consisting of a tridentate donor set for coordination of the {M(CO) 3}+ core (M = Tc, Re), and a thiol reactive maleimide group has been prepared conveniently and in high yield under Mitsunobu reaction conditions by the coupling of an appropriate alcohol derivative with maleimide. The rhenium complexes [Re(CO)3(Lx)]Br (x = 1-9) were prepared in good yields from the reactions of the ligands and (NEt4) 2[Re(CO)3Br3] in refluxing methanol. The ligands and their Re complexes were characterized by 1H and 13C NMR, IR, and ESI-MS. Ligand L4 and [Re(CO)3(L5)]Br have been structurally characterized by X-ray crystallography. Photoexcitation of solutions of the complexes [Re(CO)3(Lx)]Br (x = 4-6) gives rise to intense and prolonged luminescence at room temperature (fluorescence lifetimes of ca. 16 μs). The ligands and their Re complexes react smoothly at the maleimide linker with sulfhydryl groups of peptides and proteins at room temperature in phosphate-buffered saline (PBS, pH 7.4) to form stable thioether bioconjugates. The photoluminescence properties of the labeled conjugates are similar to those of the parent complexes, but with even longer lifetimes. The ligands can also be labeled at room temperature with 99mTc to give chemically robust complexes. The corresponding hydrazinonicotinamide derivative N-[5-(6′-hydrazinopyridine-3′-carbonyl)aminopentyl]-maleimide (L10) was also prepared. While coupling of L10 to cysteine ethylester and synthesis of the rhenium derivative [ReCl3(HYNIC-maleimide)2] were successfully accomplished, attempts to couple [ReCl3(HYNIC-maleimide) 2] to glutathione or BSA yielded intractable mixtures.

Original languageEnglish (US)
Pages (from-to)3886-3897
Number of pages12
JournalDalton Transactions
Issue number24
DOIs
StatePublished - Dec 21 2005

ASJC Scopus subject areas

  • Inorganic Chemistry

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