Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).
Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues.
Department of Chemistry, Washington State University , P.O. Box 644630, Pullman, Washington 99164, United States.
Shalina C
SC
Bottorff
Benjamin B
BB
Kasten
Jelena
J
Stojakovic
Adam L
AL
Moore
Leonard R
LR
MacGillivray
Paul D
PD
Benny
D002614:Chelating Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D057930:Click Chemistry; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D007555:Isoxazoles / Q000737:chemistry*; D008024:Ligands; D015609:Organotechnetium Compounds / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*
D002614:Chelating Agents; D007555:Isoxazoles; D008024:Ligands; D015609:Organotechnetium Compounds; D012211:Rhenium; D003300:Copper