Evaluating the Aqueous Stability of Alkyl‐/Aryl‐Hydrosilanes by NMR Spectroscopy and GC‐MS

The incorporation of hydrosilanes as a carbon bioisostere in bioapplied molecules is under-explored. In this study, the aqueous stability at neutral pH of representative alkyl-/aryl-hydrosilanes is investigated using NMR spectroscopy and GC-MS.The aggregate data analysis reveals which Si-H bonds are susceptible to hydrolysis, which will inform future organosilane design in bioapplied molecules.

Hydrosilanes are commonly used as reducing agents or as synthetic precursors for silanols. However, the incorporation of hydrosilanes as carbon bioisosteres is underexplored. In this study, the hydrolytic stability of ten variably substituted hydrosilanes—including monoaryl, monoalkyl, diaryl, dialkyl, alkyl aryl, triaryl, trialkyl, dialkyl aryl, and alkyl diaryl silanes—is investigated using five complementary methods, including ¹H–NMR time-lapse and GC-MS experiments, at neutral pH. The ¹H–NMR time-lapse experiments suggest that monoaryl and monoalkyl silanes are susceptible to hydrolysis, as evidenced by 31% and 22% reduction in starting material, respectively, over 24 h. Other investigated silanes are resistant to hydrolysis in these solvent systems for at least 24 h. The GC-MS experiments quantitatively support the respective reactivity of these hydrosilanes at pH 7. Lastly, the reactivity of selected hydrosilanes is evaluated at pH 7.4 phosphate-buffered saline buffer; only monoalkyl silanes degraded in the presence of the added salt content. Overall, the study demonstrates that hydrosilanes exhibit hydrolytic stability at neutral pH, except for monoaryl- and monoalkyl-substituted silanes, which are susceptible to degradation. The results provide insight into the likelihood of the SiH bond surviving in aqueous environments, opening the door for a wider variety of silicon-containing molecules in drug discovery.

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