# Nucleobase-Containing Polymers: Structure, Synthesis, and Applications
## 3 Synthetic Nucleobase-Containing Polymers
### Synthesizing Nucleobase Polymers by RAFT  
As popular as ATRP, the RAFT (reversible addition-fragmentation chain transfer) process, which was first introduced by the group of [PERSON] [48] in 1998, is also recognized as one of the most versatile methods for producing a wide range of macromolecules with well-defined functionalities and complex architectures.  
In 2013, [PERSON] et al. synthesized methacryloyl-monomers containing adenine and thymine to yield homopolymers and copolymers with excellent control over molecular weight and end group fidelity via RAFT polymerization (shown in Figure 2) [49]. Their results indicated that the polymerization solvent greatly affected the monomer reactivity; for example, chloroform promoted hydrogen bonds between the adenine monomers and thymine monomers, preferring moderate alternating copolymers, while solvent DMF suppressed these interactions, preferring statistical copolymers. Furthermore, they investigated the self-assembly properties of the copolymers and their TEM and DLS results clearly indicated that the presence or absence of hydrogen bonding between nucleobases could influence the morphology of forming micelles. Similarly, the same group explored more nucleobase-containing materials via RAFT dispersion polymerization in 1,4-dioxane and chloroform, and also investigated the behavior of copolymers self-assembly [29]. The results confirmed again that the morphologies of self-assembled nucleobase-containing polymers were dependent on polymerization solvents. For example: spherical micelles with internal structures were only observed in chloroform by varying the \(DP\) of the core-forming block. As an extension of this work, in 2015 they reported the synthesis and self-assembly of thymine-containing polymers via RAFT dispersion polymerization and a wide variety of morphologies were accessed by changing the different solvent of polymerization or incorporating adenine-containing mediators [50]. These results strongly demonstrated that nucleobase interactions played a central role in controlling the shape and size of polymeric self-assemblies.  
Figure 2: Synthesis and self-assembly of adenine and thymine block copolymers using RAFT [49]. Reproduced with permission. Copyright American Chemical Society, 2013.  
[PERSON] et al. used a similar RAFT polymerization strategy to synthesize well-defined acrylic ABA triblock copolymers with nucleobase-functionalized external blocks and poly(\(n\)-butyl acrylate) (PnBA) as a central block (shown in Scheme 3) [31]. Moreover, they prepared triblock copolymer films and supramolecular blend and their results indicated that the acrylic monomer with a flexible spacer to the pendant nucleobases promoted intermolecular recognition of nucleobases, lowering the \(T_{\text{g}}\) of functionalized polymers. In addition, the complementary hydrogen bonding between adenine and thymine formed a thermally labile, physically crosslinked network that exhibited enhanced mechanical performance with melt processability, and the supramolecular blend exhibited a cylindrical microphase-separate morphology. More and more work has been using RAFT as an efficient and robust method for the preparation of multi-block polymers with nucleobase functionalities, and more and more morphologies have been accessed by fine tuning of the interactions between nucleobases [30; 32; 51]. RAFT has been the most frequently used living polymerization method in preparing nucleobase-containing polymers; however, it is still worth noting some challenges of this method. For example, RAFT usually requires careful selection of chain transfer agents (CTAs) for each monomer, which may require screening of CTAs before the polymerization of different nucleobase-containing monomers.