Structural and Kinetic Considerations for the Application of the Traceless Staudinger Ligation to Future ¹⁸F Radiolabeling Using XRD and ¹⁹F NMR

Abstract

A 4-fluorobenzoate-functionalized phosphane was synthesized and reacted with different azides using the traceless Staudinger ligation as a representative sample reaction for future radiolabeling purposes with short-lived radionuclides like fluorine-18. For this purpose, the reaction rate was evaluated at different temperatures. The effect of starting material concentrations and the influence of the steric effect coming from the applied azides were investigated. 19 F NMR was used to determine the reaction half-live (τ 1/2 ) and the reaction rate constant (k obs ) of this ligation under mild reaction conditions in a water-acetonitrile mixture. Furthermore, the phosphane key compound 1 (orthorhombic, space group Pna2 1 , a = 18.6363(9), b = 8.3589(4), c = 18.5480(9)Å, V = 2889.4(2)Å 3 , Z = 8, D obs = 1.277 g/cm 3 ), which acts as starting material for all subsequent syntheses, and the fluorine-containing phosphane 3 (monoclinic, space group P2 1 /c, a = 8.321(2), b = 16.160(4), c = 14.940(4)Å, β = 99.51(1)°, V = 1981.4(8)Å 3 , Z = 4, D obs = 1.342 g/cm 3 ) were analyzed by single-crystal XRD.

The Staudinger Ligation

“…The entries are organized by number of carbon atoms of the phosphane (and then grouped by publication), and it will cover examples up to beginning of 2020 (for not or only partly covered examples, see refs − ).…”

Bioorthogonal Reactions of Triarylphosphines and Related Analogues

“…The high chemoselectivity of the reaction permits its use in the presence of native, unprotected biomolecules. In one example, the traceless Staudinger ligation was used to attach position emission tomography (PET) tags to small molecules. , Phosphines comprising radioactive 18 F- or 131 I-labeled acyl chains were incubated with azide-bearing pharmaceutical agents. ,− The PET-tagged products could be used immediately for in vivo imaging. The products did not require purification owing to the mild nature of the ligation and lack of toxic byproducts.…”