Synthesis of sequence-defined nucleobase acrylate oligomers via RAFT polymerization

Abstract

Nucleobases are well known functionalities in nature which have an important role in biomolecules such as DNA and RNA. The potential of sequence-defined (SD) nucleobase acrylate functionalized oligomers lies not only in mimicry of these biomolecules, but also in its application as a molecular sensor, a tag or even as a chemical data unit.

Synthesis and purification of the first single unit monomer insertion (SUMI) with adenine functionalized acrylate monomer (AAM) is the main goal of this project. Firstly, synthesis of adenine as well as cytosine functionalized acrylate monomers was performed with corresponding yields of 55-68% and 42%. Secondly, different reaction parameters such as reaction time, RAFT agent, concentration, solvent and starting product equivalents were varied to find the ideal reaction conditions for the first AAM SUMI synthesis. Thymine as well as cytosine acrylate monomer SUMI synthesis was performed using these ideal conditions as a proof of concept. Thirdly, a flash chromatography purification method was developed for the crude AAM SUMI product. Products were analysed using 1H-NMR spectroscopy and ESI-MS.

Optimization of the reaction parameters and purification method was performed. The molar ratios are monomer:CTA:initiator (5:1:0.05) when using AAM as monomer, CPD-TTC as RAFT agent and AIBN as initiator in DMSO when reacting 1h at 100 °C. A purity of 95% was achieved after purification of the SUMI product with flash chromatography when using MeOH:DCM (7:93) as mobile phase.