Structural characterisation and bioconjugation of an active ester containing oxorhenium(V) complex incorporating a thioether donor

Abstract

A simple new 2,3,5,6-tetrafluorophenyl ester containing diamide–thioether–thiol bifunctional chelating agent LH₃, HS(CH₂)₂SCH₂C(O)NHCH₂C(O)NH(CH₂)₃C(O)OC₆HF₄, has been synthesised. The key intermediates were prepared using standard peptide chemistry procedures. Reaction of LH₃ with [Bu₄N][ReOCl₄] formed an uncharged oxorhenium(V) complex, which was characterised by X-ray structural analysis. The five-co-ordinate complex showed approximately square-pyramidal geometry with an apical oxo group and a basal ligand set comprising a deprotonated thiol group, two deprotonated amide groups, and a thioether group. A second complex of stoichiometry [ReO(LH₂)₂]Cl was formed by reaction of LH₃ with a rhenium(V) gluconate intermediate in water at pH 4.7. The 1∶1 complex [ReOL] was conjugated with the small protein N-TIMP-2 by aminolysis at a lysine residue, to form a 1∶1 adduct as established by electrospray mass spectrometry.

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