Combining Bifunctional Chelator with (3 + 2)-Cycloaddition Approaches: Synthesis of Dual-Function Technetium Complexes

A new concept for the synthesis of dual-functionalized
technetium
(Tc) compounds is presented, on the basis of the reactivity of fac-{TcVIIO3}+ complexes.
The concept combines the “classical” bifunctional chelator
(BFC) approach with the new ligand centered labeling strategy of fac-{TcO3}+ complexes with alkenes
((3 + 2)-cycloaddition approach). To evidence this concept, fac-{99TcO3}+ model complexes
containing functionalized 1,4,7-triazacyclononane (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)­acetamide (tacn-ba) and
2,2′,2″-(1,4,7-triazonane-1,4,7-triyl)­triacetic acid
(nota·3H) were synthesized and characterized. Whereas [99TcO3(tacn-ba)]+ [2]+ can be synthesized following a established oxidation procedure starting
from the TcV complex [99TcO­(glyc)­(tacn-ba)]+ [1]+, a new synthetic pathway for
the synthesis of [99TcO3(nota)]2‑ [5]2‑ had to be developed, starting
from [99Tc­(nota·3H)­(CO)3]+ [4]+ and using sodium perborate tetrahydrate (NaBO3·4H2O) as oxidizing reagent. While [99TcO3(nota)]2‑ [5]2‑ is a very attractive candidate for the development of trisubstituted
novel multifunctional radioprobes, (3 + 2)-cycloaddition reactions
of [99TcO3(tacn-ba)]+ [2]+ with 4-vinylbenzenesulfonate (styrene-SO3–) demonstrated the suitability of monosubstituted
tacn derivatives for the new mixed “BFC-(3 + 2)-cycloaddition”
approach. Kinetic studies of this reaction lead to the conclusion
that the alteration of the electronic structure of the nitrogen donors
by, e.g., alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.