## 7 Silicon Building Blocks Containing H, OH and Alkoxy moieties as Leaving Groups
After careful consideration of the obtained data, a linear relationship between the Si-F bond length difference between structure _ii_ and _iii_ and the corresponding half-lives were found to be reliable predictors of stability. However, the model was constructed on the simplified assumption that the hydrolytic half-lives are most probably impacted by kinetic and/or equilibrium effects, depending on the steric hindrance imparted by the organic rests attached to the Si atom. The radioactive labeling of the corresponding alkoxyl- and H-derivatized silanes demonstrated that steric hindrance impedes an easy access of the \({}^{18}\)F\({}^{-}\) ion and reduces radiochemical yields. Even at 90 \({}^{\circ}\)C, the labeling precursor of **23**, bearing an H atom as leaving group, could only be labeled in 48% radiochemical yield. In all investigated cases, where either the H- or alkoxyl-derivatized silanes were used as precursors, an amount of 5 mg was used, which is a substantial amount that has to be separated by preparative HPLC after the reaction if the \({}^{18}\)F-labeled fluorosilane is required in pure form. The labeling experiments were extended to peptides which will be discussed in Section 8. **8. Peptides**  
Peptides, having an intermediate size between small molecules and proteins, normally show a relatively high stability towards even harsh labeling conditions, making a one-step labeling feasible. However, the many different unprotected functional groups of the amino acid side chains can possibly hamper a selective one-step \({}^{18}\)F-introduction by nucleophilic substitution. Therefore, \({}^{18}\)F-labeling reactions of peptides normally imply multistep syntheses consisting of the production of a secondary labeling precursor bearing the F-18 label, which has then to be reacted with the peptide. Although the synthesis of several secondary labeling precursors has been improved in recent years, yielding the labeled peptides in high yields and relatively short reaction times, the multi-step syntheses of \({}^{18}\)F-labeled peptides using these synthons still require long preparation times--which is unfavorable, considering the short half-life of \({}^{18}\)F--as well as complex and costly in terms of technical equipment [34, 35, 36]. An alternative to the conventional secondary labeling precursor approach is the recently developed technique to introduce \({}^{18}\)F by reaction with Al\({}^{3+}\) and the subsequent complication of the system formed by NOTA and NO2A derivatives or the \({}^{18}\)F-labeling of the preformed Al-NOXA complex [8, 11, 12, 37] This method allows for a one-step and straightforward introduction of \({}^{18}\)F-fluoride, even into complex peptidic compounds at elevated temperatures of 100-110\({}^{\circ}\)C within 15 min, and will probably attract increasing attention within the next years. A modification of this technique involving the use of a NO2A chelator derivatized with a maleimide functionality also allowed for protein \({}^{18}\)F-labeling in a two-step labeling reaction applying _i_) the fast complication of Al-\({}^{18}\)F by the chelator and _ii_) the efficient conjugation of the formed complex to the studied antibody fragment [12]. Another alternative to the use of conventional C-\({}^{18}\)F secondary labeling precursors is the SiFA-technique for introduction of \({}^{18}\)F into peptides. There, the \({}^{19}\)F against \({}^{18}\)F isotopic exchange reaction on the SiFA moiety proved to be applicable for the one-step introduction of \({}^{18}\)F even into complex molecules such as peptides. The isotopic exchange is thereby so efficient that it takes place even at room temperature and within short reaction times, as demonstrated on the example of the clinically relevant peptide Tyr\({}^{3}\)-octreotate (TATE). The labeled compound **29** (Figure 9) was obtained in high radiochemical yields (RCYs) of 55-65% after purification and within 25 min overall synthesis time [28].