The Preparation of Nucleoside-Functionalized Silicone and Oligonucleotide-Silicone Copolymers

Abstract

<p> Attempts to prepare silicone oligonucleotide copolymers are complicated by the large difference in hydrophobicity in the two materials. Two approaches were followed to overcome this challenge. Initially, highly sterically hindered tetraisopropyldisiloxanes were used to bind 5'-0-(4,4'-dimethoxytrityl)-thyrnidine at the 5'-0H. These compounds proved to be hydrolytically more stable than the analogous dimethylsiloxane compounds, which were also prepared. Alternatively, Si-C bonds, which are hydrolytically stable, can be used to bind the two species together. Introduction of allyl ether by traditional Williamson conditions was followed by hydrosilylation with hydride terminated (Si-H) silicone, catalyzed by using platinum complexes, to give the nucleoside-functionalized silicone. We also introduced an epoxy group to one end of a silicone chain and found it to be stable to hydrolysis. Once the epoxy group binds nucleoside-functionalized silicone to solid phase, it is expected that the nucleoside-functionalized silicone via a trimethylene spacer linkage might be a starter for preparation of oligonucleotide-functionalized silicones in future work. </p>