# Nucleobase-Containing Polymers: Structure, Synthesis, and Applications
## 3 Synthetic Nucleobase-Containing Polymers
### Synthesizing Nucleobase Polymers by ATRP  
Since Atom Transfer Radical Polymerization (ATRP) was independently discovered by [PERSON] and [PERSON] et al. (2005, 2010) in 1995, by virtue of affording polymers of narrow molecular weight distributions, high molecular weight, and advanced macromolecular architectures, it presents a powerful method to prepare a great variety of polymers, including nucleobase-contained polymers. [PERSON] et al. utilized ATRP to synthesize a series of well-defined poly(ethylene glycol), (PEG)-poly(adenine) and PEG-poly(thymine) nucleobase containing block co-polymers from a PEG-based macroinitiator ([PERSON] and [PERSON], 2009). Nucleobase-functionalized monomer (thymine and/or adenine), catalyst (CuCI), ligand (bpy) and PEG-based macroinitiator (stoichiometric) were mixed and underwent typical ATRP procedures. The expected conversion was analyzed by \({}^{1}\)H-NMR spectroscopy. Finally, the reaction was quenched by 1-phenyl-1-(trime-thysiloxy)ethylene (showed in Scheme 1). Furthermore, to demonstrate the unique properties of the nucleobases in the sidechain, they investigated the aggregation behavior of two complementary block copolymers in water (The structure of assembled copolymers is shown in Scheme 1). They found an interaction between the complementary thymine and adenine moieties, which resulted in an increased solubility of the block copolymers by an improved shielding of the hydrophobic blocks. In 2007, the same group reported the synthesis and controlled polymerization of all four nucleobases' (thymine, adenine, cytosine, and guanine) methacrylate monomers through ATRP method ([PERSON] and [PERSON], 2009). Technically, by alkylation of the nucleobases with 3-bromopropyl methacrylate, thymine-, adenine-, cytosine-, and guanine-functionalized methacrylate monomers were prepared and their ATRP kinetics were examined. Interestingly, they found the formation of guanine and cytosine monomer with copper(II), and these two specific polymerizations required more addition of catalyst and the use of PMDETA. From this study, all four unprotected nucleobase monomers could be polymerized in a controlled manner, but there is still space for improving the level of control in the synthesis of nucleobase-containing polymers through ATRP. Similarly, [PERSON] et al. (2010) synthesized poly[1-(4-vinylbenzyl)thymine] (PVBT) through ATRP at a high temperature (showed in Scheme 2) and, furthermore, performed nucleobase recognition through adding presynthesized 9-hexadecyladenine (A-C16) in the presence of polythymine homopolymers. Specifically, due to the hydrogen bonding interactions between the thymine groups of PVBT and \begin{table}
\begin{tabular}{|c c c c|} \hline
**Polymerization method** & **NB-Monomer** & **Length** & **References** \\ \hline \multicolumn{4}{|c|}{Styrenes and derivatives} \\ \multicolumn{4}{|c|}{Acrylates} \\ ATRP & Methacrylates & 10–100 bases & [25; 26; 27] \\  & (Meth)acrylamides & & \\  & Miscellaneous monomers & & \\ \hline \multicolumn{4}{|c|}{Styrenes and derivatives} \\ \multicolumn{4}{|c|}{RAFT} & Acrylates & \\  & Methacrylates & 10–100 bases & [28; 29; 30; 31; 32] \\  & (meth)acrylamides & & \\ \hline NMP & Styrenes and derivatives & & \\ \hline NMP & Acrylates & 20–100 bases & [33; 34] \\ \hline Conventional radical polymerization & Common monomers & 80–200 bases & [35; 36; 37] \\ \hline \multicolumn{4}{|c|}{Azides} \\ \multicolumn{4}{|c|}{Alkynes} \\ \multicolumn{4}{|c|}{Click chemistry} & Thios \\ \multicolumn{4}{|c|}{Vinyls} \\ \multicolumn{4}{|c|}{Acrylamides} \\ \multicolumn{4}{|c|}{Dienes} \\ \multicolumn{4}{|c|}{Ring opening polymerization} & Cyclic monomers (e.g., cyclic & \\  & olefins, acetals, lactams, lactones) & 10–40 bases & [41; 42; 43] \\ \hline Other polymerization & Thiophenes and derivatives & N.A. & [44] \\ \hline \end{tabular}
\end{table} 
Table 1: Common methods for the preparation of NB-containing polymers. the adenine group of A-C16, the biocomplementary PVBT/A-C16 hierarchical supramolecular complexes were formed in dilute DMSO solution.