Direct <sup>18</sup>F-Labeling of Biomolecules via Spontaneous Site-Specific Nucleophilic Substitution by F<sup>–</sup> on Phosphonate Prostheses
Chao Wang, Lei Zhang, Zhaobiao Mou, Wanru Feng, Zhongjing Li, Zhongjing Li, Hongzhang Yang, Xueyuan Chen, Shengji Lv, Zijing Li, Zijing Li
Abstract
We describe a high radiochemical yield late-stage direct 18F-labeling of bare biomolecules containing common active groups. Spontaneity and site-selectivity are attributed to the remarkably higher rates of nucleophilic substitution reactions on phosphonates than on other electrophiles by F– at various hydrogen bond forms. Rapid access to many medicinally significant 18F-labeled biomolecules is achieved at 21–68% radiochemical yields and 35.9–55.1 GBq μmol–1 molar activities both manually or automatically.
Topics & Concepts
ChemistryBiomoleculeNucleophilePhosphonateYield (engineering)ElectrophileNucleophilic substitutionCombinatorial chemistrySelectivitySubstitution reactionStereochemistryMolar ratioMedicinal chemistryOrganic chemistryCatalysisBiochemistryMaterials scienceMetallurgyChemical Synthesis and AnalysisRadiopharmaceutical Chemistry and ApplicationsPeptidase Inhibition and Analysis