Sequence-Controlled Synthesis of Advanced Clickable Synthetic Oligonucleotides.

Through thiol-ene photopolymerization of presynthesized oligomers, advanced clickable nucleic acids (CNA-2G) are synthesized with sequence-controlled repeating units. As examples, poly(thymine-adenine) (polyTA) CNA-2G and poly(thymine-thymine-cytosine) CNA-2G are synthesized by polymerizing thiol-ene heterofunctional dimers with pendant thymine-adenine nucleobases and trimer with pendant thymine-thymine-cytosine nucleobases. Based on size exclusion chromatography (SEC) analysis, polyTA and polyTTC have number average molecular weights of 2000 and 1800, respectively, which contain 7-8 pendant nucleobases. Based on the different behavior of the CNA-2G monomers and CNA-2G oligomers with two or more pendant nucleobases in photopolymerization, an unusual thiol-ene chain-growth propagation mechanism is observed for the former and a common thiol-ene step-growth propagation mechanism for the latter. The uncommon thiol-ene chain-growth propagation is hypothesized to rely on a six-membered ring mediated intramolecular hydrogen atom transfer process.