Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium...

Area of Science:

• Radiochemistry and Nuclear Medicine
• Coordination Chemistry
• Organic Synthesis

Background:

• Development of dual-functionalized technetium (Tc) compounds is crucial for advanced radiotracers.
• Existing methods often rely on bifunctional chelator (BFC) approaches.
• Novel strategies are needed to expand the toolkit for Tc-based radiopharmaceutical synthesis.

Purpose of the Study:

• To present a new concept for synthesizing dual-functionalized technetium (Tc) compounds.
• To combine the classical BFC approach with a ligand-centered labeling strategy using fac-{TcO3}+ complexes and alkenes via (3+2)-cycloaddition.
• To demonstrate the feasibility of this mixed approach using functionalized 1,4,7-triazacyclononane (tacn) derivatives.

Main Methods:

• Synthesis and characterization of fac-{(99)TcO3}+ model complexes with functionalized tacn derivatives (tacn-ba and nota).
• Development of a new synthetic pathway for [(99)TcO3(nota)](2-) using sodium perborate tetrahydrate as an oxidizing agent.
• Investigation of (3+2)-cycloaddition reactions between [(99)TcO3(tacn-ba)](+) and 4-vinylbenzenesulfonate.

Main Results:

• Successfully synthesized and characterized fac-{(99)TcO3}+ complexes with tacn-ba and nota derivatives.
• Established a new synthetic route for [(99)TcO3(nota)](2-), highlighting its potential for multifunctional radioprobes.
• Demonstrated the suitability of monosubstituted tacn derivatives for the mixed BFC-(3+2)-cycloaddition approach via kinetic studies.

Conclusions:

• The presented concept effectively combines BFC and ligand-centered labeling strategies for dual-functionalized Tc compound synthesis.
• Functionalized tacn derivatives are suitable for this novel mixed approach, enabling tunable reaction rates.
• This work opens new avenues for developing advanced, multifunctional Tc-based radiotracers.