CO2-Driven stereochemical inversion of sugars to create thymidine-based polycarbonates by ring-opening polymerisation

Abstract

The development of biodegradable polymers from renewable resources is vital in addressing the dependence of plastics on petroleum-based feedstocks and growing ocean and landfill waste. Herein, both CO₂ and natural sugar diols are utilised as abundant, safe and renewable building blocks for the synthesis of degradable and biocompatible aliphatic polycarbonates. Despite a strong potential for advanced polymer properties, inspired by Nature's supramolecular base-pairing, polycarbonates from the sugar components of DNA, 2′-deoxyribonucleosides have been limited by the inability of phosgene derivatives to form the cyclic carbonate monomers that would allow for controlled ring-opening polymerisation. CO₂ insertion at 1 atm pressure into methylated thymidine 2′-deoxyribonucleoside, facilitated by organic base 1,8-diazabicyclo-[5.4.0]-undec-7-ene, affected an intramolecular S_N2-like displacement of a tosyl leaving group to yield the cyclic carbonate by stereochemical inversion. Organocatalytic ring-opening polymerisation proceeded rapidly in solution resulting in high monomer conversions of 93% and number-average molecular weights, substantially greater and more controlled than via polycondensation routes. The thermodynamic parameters of the polymerisation (ΔH_p = −12.3 ± 0.4 kJ mol⁻¹ and ΔS_p = −29 ± 1.1 J mol⁻¹ K⁻¹) were determined from the equilibrium monomer conversions over a temperature range of 0 to 80 °C and pseudo-first order kinetics demonstrated. The amorphous thymidine-based polycarbonates exhibited high glass transition temperatures of 156 °C and were found to be highly degradable to the constituent diol under basic aqueous conditions. Static water contact angle measurements and cell studies with MG-63 cell line indicated slightly hydrophilic and biocompatible materials, promising for tissue-engineering applications. The novel, CO₂-driven approach to cyclic carbonate synthesis represents a means of expanding the scope of sugar-based monomers for tailored material properties derived from natural products.