Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

Synthetic chemists have devoted tremendous effort towards the production of precision synthetic polymers with defined sequences and specific functions. However, the creation of a general technology that enables precise control over monomer sequence, with efficient isolation of the target polymers, is highly challenging. Here, we report a robust strategy for the production of sequence-defined synthetic polymers through a combination of liquid-phase synthesis and selective molecular sieving. The polymer is assembled in solution with real-time monitoring to ensure couplings proceed to completion, on a three-armed star-shaped macromolecule to maximize efficiency during the molecular sieving process. This approach is applied to the construction of sequence-defined polyethers, with side-arms at precisely defined locations that can undergo site-selective modification after polymerization. Using this versatile strategy, we have introduced structural and functional diversity into sequence-defined polyethers, unlocking their potential for real-life applications in nanotechnology, healthcare and information storage

Iterative synthesis of uniform poly(ethylene glycol) via organic solvent nanofiltration

This thesis describes the synthesis of uniform, heterobifunctional poly(ethylene glycol) via organic solvent nanofiltration, a scalable and cost-effective membrane-based technology that allows reactions and purifications to be carried out in liquid medium throughout and provides access to oligomers of commercially relevant length. This membrane-based strategy contrasts with established routes via chromatography, extraction and solid phase synthesis. The preparation of uniform oligomers relies on the stepwise addition of building blocks, one at a time, over many synthetic extension cycles. To ensure uniformity, the growing oligomer requires purification from excess building block and reaction debris after each extension. In this strategy, intermediate and final products en route to the desired poly(ethylene glycol) oligomer are freed from impurities by diafiltration. In order to facilitate the removal of impurities during diafiltration, multiple oligomers are synchronously grown on a soluble, multivalent anchor. The attachment of multiple growing oligomers onto the anchor leads to a fast-growing product complex with enough size to be well-retained by a membrane. On the other hand, the separable impurities consisting of much smaller building block and reaction debris can readily pass through the membrane, resulting in an efficient separation. To enhance discrimination, the anchor is enlarged, and the size of the functional groups on the building block minimized. Further, the anchor is designed to be sufficiently distinct and readily detectable by UV. A two-stage diafiltration process then allowed the synthesis of uniform, mono-methyl Eg60 (mPEG-2700) with excellent quality (dispersity Đ = 1.0006, oligomer purity = 97 %) from an Eg12 building block in four chain extension cycles. It is demonstrated that deprotection and purification may be accomplished jointly via nanofiltration with a poly(ether ether ketone) membrane that is sufficiently stable towards acidic deprotection conditions and that spent diafiltration solvent may be partially recovered by membrane-based solvent recovery in a closed loop.Open Acces

Author Correction: Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

Correction to: Nature Chemistry https://doi.org/10.1038/s41557-018-0169-6, published online 3 December 2018