Thiourea derivatives as chelating agents for bioconjugation of rhenium and technetium

Abstract

Potential tetradentate thiocarbamoylbenzamidine derivatives H₄L have been synthesized from the corresponding benzimidoyl chlorides and triglycine. They are suitable chelating agents for the oxidotechnetium(V) and oxidorhenium(V) cores and form stable, neutral [MO(HL)] complexes with an equatorial SN₃ coordination sphere and an additional, uncoordinated carboxylic group, which can be used for bioconjugation. Representatives of the rhenium and ⁹⁹Tc products have been isolated and analyzed with spectroscopic methods and X-ray diffraction. Bioconjugates of these complexes with angiotensin-II have been synthesized and structurally characterized. Analogous ^99mTc complexes have been produced and tested in vitro and in vivo. The experiments confirm a considerable stability for the [^99mTc(HL)] product as well as for its bioconjugate and recommend this class of compounds for further bioconjugation studies towards clinical applications.