Thesis advisor: Larry W. McLaughlin / Thesis advisor: Mary F. Roberts / Nucleic acids are the only biopolymers capable of encoding and transferring information, this property has placed them at the fundamental core of all living organisms, and made them a topic of intense research for over a century. The former studies in our laboratory on simplified nucleic acid backbones provided insight into how we might rationally alter nucleic acid structure into one that possesses properties not observed in natural DNA and RNA. Here the work began as an investigation into rigidified nucleic acid systems capable of functioning as DNA. The first rigidified nucleic acid system we designed, the cyclo-2'-deoxynucleic acids, has a linkage between the C5' of the ribose sugar and base to lock the ӽ angle into the similar angle as the native nucleoside. These rigidified bases show great impact towards the DNA structure, destabilizing double helix formation. This in fact can also be found in nature to inhibit the TATA binding protein associating with its target region. The next generation of rigidified nucleosides has an extended 7-membered ring instead of the 6-membered ring that was present in the first generation to push the base closer to the helical center. Both diastereomers of the ring-expanded-cyclo-2'-deoxyadenosine have been successfully synthesized and characterized and are ready to perform further studies. The third system is the hydroxymethyl-cyclo-nucleosides. The modified nucleosides in this project not only have the same linkage as the cyclo-nucleosides in the first system to restrict the base rotation, but also have an extra carbon (C6') to give the backbone more flexibility which might better stabilize a double helix than the first generation. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.