Organofluorosilanes as Model Compounds for 18 F‐Labeled Silicon‐Based PET Tracers and their Hydrolytic Stability: Experimental Data and Theoretical Calculations (PET=Positron Emission Tomography)

Water stable! Radiochemists have recently discovered silicon chemistry as a tool for the introduction of 18 F into biomolecules for positron emission tomography (PET) imaging. 18 F‐labeled PET tracers must be stable towards defluorination under physiological conditions. Here, a theoretical model of organofluorosilane hydrolysis is developed that correlates with the experimentally determined hydrolytic half‐lives and allows estimation of the stability of newly designed compounds (see scheme).Silicon chemistry has only recently been discovered by radiochemists as a straightforward tool for the introduction of 18 F into biomolecules for positron emission tomography (PET) imaging. 18 F‐labeled PET tracers must be stable towards defluorination under physiological conditions, but it is known that the hydrolytic stability of the silicon–fluorine bond is determined by the nature of the substituents on silicon. In the presented study we performed an extensive investigation on the hydrolytic stability of various synthesized organofluorosilane model compounds. By means of density functional theory (DFT) methods a theoretical model of organofluorosilane hydrolysis, which correlates with the experimentally determined hydrolytic half‐lives, is developed. The calculation of the difference of SiF bond lengths between the optimized structures of the starting material A and the intermediate structure C allows the estimation of the hydrolytic stability of newly designed compounds. This model permits the facilitated development of improved building blocks for the synthesis of novel 18 F‐silyl‐modified biomolecules for PET imaging.