Synthesis of nucleobase functionalised block copolymers towards precision self-assembly

Abstract

The formation of nanoaggregates from continuous flow assembly of nucleobase-functionalized amphiphilic block co-polymers is investigated. Block copolymers (BCPs) made from nucleobase-conjugated acrylate monomers and PEG acrylate were synthesized via reversible addition fragmentation chain transfer polymerization (RAFT) and tested. Polymers containing adenine, thymine, cytosine and uracil were obtained. Close inspection of the block extensions revealed potential issues in the livingness of the polymers, which may, however, only be an artifact from the high aggregation of polymers even in size exclusion chromatography. Using different synthesis methods (varying the order of polymer blocks and using in situ one-pot recipes) leads to very similar nanoaggregates with highly consistent results. Nanoaggregates were formed using a highly reproducible flow mixing setup, which enables not only fast but also scalable nanoparticle formation. By using complementary and non-complementary nucleobase BCPs, nanoparticles of very different sizes can be obtained in aqueous solution, ranging from about 35 to 230 nm, whose size distribution can be related to diffusion coefficients obtained for the polymers and their blends in a homogeneous solution via diffusion ordered spectroscopy. Further tunability of the system was shown by changing the average degree of polymerization of the nucleobase block from 25 to 60, demonstrating a transition from small spherical particles to elongated worm-like morphologies. Overall, this study gives guidelines for the targeted synthesis of nucleobase-containing nanoparticles with high tunability and under well reproducible synthesis conditions.