Syntheses of High-Valent fac-[99mTcO3]+ Complexes and [3+2] Cycloadditions with Alkenes in Water as a Direct Labelling Strategy

Abstract

Reported herein is a new concept for the labelling of biomolecules with small [^99 mTcO₃]⁺ complexes through a [3+2] cycloaddition with alkenes for radiopharmaceutical applications. We developed convenient reactions for the synthesis of small, water stable fac-[TcO₃(tacn-R)]⁺ complexes (⁹⁹Tc and ^99mTc, tacn=1,4,7-triazacyclononane, R=H, -CH₂-C₆H₅, -CH₂-C₆H₄COOH). With alkenes, these high valent [^99mTcO₃]⁺ complexes undergo [3+2] cycloaddition with formation of the corresponding Tc^V–glycolato complexes. The ^99mTc^V and ^99mTc^VII complexes are stable at 37 °C in water and in the presence of serum proteins. Therefore, new opportunities in technetium chemistry are enabled with a high potential for medicinal and biological applications. In contrast to classical labelling, the presented strategy is ligand and not metal-centred.