# Nucleobase-Containing Polymers: Structure, Synthesis, and Applications
## 3 Synthetic Nucleobase-Containing Polymers
### Synthesizing Nucleobase Polymers by Conventional Radical Polymerization  
Besides controlled polymerizations, conventional radical polymerization also allows efficient large-scale synthesis of nucleobase functionalized polymers. As early as 2005, [PERSON] et al. investigated the polymerization of a series of monomers bearing nucleobases 1-(4-vinylbenzyl)uracil (VBU), 1-(4-vinylbenzyl)thymine (VBT), and 9-(4-vinylbenzyl)adenine (VBA) [37]. The corresponding homopolymers (PVBT, PVBU, and PVBA) were prepared in high yields via conventional radical polymerization, while the copolymers of dodecyl methacrylate (DMA) with either VBT or VBA were prepared by ATRP and free radical polymerization. The results indicated that these homopolymers were not very practical due to poor solubility in most of the common organic solvents. However, copolymers of DMA with either VBT or VBA could be dissolved in a range of organic solvents. Furthermore, the formed copolymers P(VBT-_co_-DMA) and P(VBA-_co_-DMA) were found to self-assemble in dilute solutions in dioxane or chloroform, as confirmed by the hypochromicity effect in UV spectroscopy. Nevertheless, it was found that at higher concentrations of chloroform, P(VBT-_co_-DMA), P(VBA-_co_-DMA), or P(VBT-_co_-DMA)/P(VBA-_co_-DMA) mixtures spontaneously self-assembled into spherical aggregates. Later in 2006, the same group studied in detail the self-organization of random copolymers composed of a nucleobase monomer (either VBT or VBA) and DMA in dilute chloroform [35]. They investigated how the balance between the molar fractions of the nucleobase monomer and DMA could affect the solubility and self-assembly behavior of nucleobase-containing copolymers. In addition, they demonstrated that hydrogen bonding was an efficient driving force for organizing synthetic nucleobase-containing polymers in a noncompetitive solvent.  
[PERSON] presented an interesting work that created a selective macroscopic self-assembly system by using polymer gels modified with either complementary DNA oligonucleotides or nucleobase-containing polymers [36]. Specifically, hydrogels and organogels were obtained via conventional radical terpolymerization of AAm or styrene (main chain units) and MBAAm or DVB (crosslinking units) (showed in Scheme 4). The oligonucleotide-modified hydrogels exhibited macroscopic recognition between complementary strands. Similarly, nucleobase-modified organogels exhibited the same adhesion as DNA oligonucleotide-functionalized hydrogels and were visualized on a macroscopic scale. Direct adhesion between macroscopic objects by nucleobase interaction provides the possibility of creating \"smart\" materials that can bind many kinds of heterogeneous materials  
Figure 3: Synthesis of adenine and thymine nucleobase-functionalized triblock copolymers using NMP [33]. Reproduced with permission. Copyright American Chemical Society, 2007.  
without adhesives. Although conventional radical polymerization provides a very simple method for nucleobase-containing polymer synthesis (no metal catalyst, no precursors), it also has disadvantages such as insufficient control of the polymer length, polydispersity, and macromolecular structure, which may impair its potential applications in biology and materials science.  
With the inherent property of sequence recognition, [PERSON] et al. reported that the nucleobase core of a block copolymer micelle can serve as a template for controlled radical polymerization [28] (Figure 4). This uniquely templated polymerization yields unexpectedly high molecular weight polymers (up to \(\sim\)400,000 g/mol), with low polydispersity (\(P\leq 1.08\)); and their TEM imaging clearly demonstrated that polymerization takes place in the core of the micelle as its size changes from \(\sim\)13 to \(\sim\)20 nm before and after polymerization. More interestingly, the discrete micelle core structures enabled the control of the polymerization by segregation of propagating radicals.