Technetium Complexes with an Isocyano-alkyne Ligand and Its Reaction Products

Abstract

The attachment of an ethyne substituent in the para position of phenylisocyanide, CNPhpCCH, enables the isocyanide to replace carbonyl ligands in the coordination sphere of common technetium(I) starting materials such as (NBu4)[Tc2(μ-Cl)3(CO)6]. The ligand exchange proceeds under thermal conditions and finally forms the corresponding hexakis(isocyanide)technetium(I) complex. The product undergoes a copper-catalyzed cycloaddition (“Click” reaction), e.g., with benzyl azide, which gives the [Tc(CNPhazole)6]+ cation. The free, uncoordinated “Click” product is obtained from a reaction of the corresponding tetrakis(CNPhazole)copper(I) complex and NaCN. It readily reacts with mer-[Tc(CO)3(tht)(PPh3)2](BF4) (tht = tetrahydrothiophene) under exchange of the thioether ligand. Alternatively, [Cu(CNPhazole)4]+ can be used as a transmetalation reagent for the synthesis of the hexakis(isocyanide)technetium(I) complex, which is the preferable approach for the synthesis of the technetium complex with the short-lived nuclear isomer 99mTc, and a corresponding protocol for [99mTc(CNPhazole)6]+ is reported. The 99Tc and copper complexes have been studied by single-crystal X-ray diffraction and/or spectroscopic methods including IR and multinuclear NMR spectroscopy.

[Tc(NO)(Cp)(PPh3)Cl] and [Tc(NO)(Cp)(PPh3)(NCCH3)](PF6), and Their Reactions with Pyridine and Chalcogen Donors

“…Molecules relevant for such applications frequently possess a reactive group in their periphery on which targeting biomolecules can be attached. Carboxylic or amino groups allow common peptide couplings, but also click reactions and the formation of thiourea linkers via isocyanates have been utilized [ 107 , 114 , 115 , 116 ].…”

Radiosynthesis and Bioevaluation of 99mTc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging

“…The organ uptakes of the [ 99m Tc]Tc-CNnUBI 29-41 complexes and [ 99m Tc]Tc(CO) 3 -CNnUBI 29-41 complexes at the bacterial infection site were significantly greater than that of [ 99m Tc]TcN-CNnUBI 29-41, which may be related to the overall charge properties of the complex and the valence of technetium. The [ 99m Tc]Tc-CNnUBI 29-41 complexes and [ 99m Tc]Tc(CO) 3 -CNnUBI 29-41 complexes had a +1 valence charge overall [31], while the [ 99m Tc]TcN-CNnUBI 29-41 complexes were electrically neutral [43]. Molecules with positive charges are more likely to bind to negatively charged bacterial surfaces.…”

“…Molecules with positive charges are more likely to bind to negatively charged bacterial surfaces. Secondly, the valence of technetium in the [ 99m Tc]Tc-CNnUBI 29-41 complexes and [ 99m Tc]Tc(CO) 3 -CNnUBI 29-41 complexes is +1 [31], while the valence of technetium in the [ 99m Tc]TcN-CNnUBI 29-41 complexes is +5 [32,43]. The valence of technetium in the technetium complex may also have a significant impact on the biodistribution properties and images.…”

“…The final compounds were identified by electrospray ionization mass spectrometry (ESI-MS), and the purity of the compounds was analyzed by high-performance liquid chromatography (HPLC); all the compounds were >94% pure (Figures S1-S10). The isocyanide group (-N≡C) is a common bifunctional linker used for 99m Tc labeling, which is formed when the isocyanide group coordinates with technetium, not only through a σ-coordinate bond but also through a π-feedback bond, which is a strong coordination group [30,31]. Isocyanide derivatives can coordinate different 99m Tc cores, such as the [ 99m Tc]Tc(I) + core, [ 99m Tc][Tc(I)(CO)3(H2O)3] + core and [ 99m Tc][Tc(V)N] 2+ core, to form various well-stable 99m Tc-labeled complexes with different lipophilicities and biometabolic properties [32].…”