Solvent effects in the enzymatic synthesis of poly(glycerol adipate): a design of experiments approach toward sustainable media

Abstract

The identification of sustainable reaction media remains a central challenge in enzymatic polymer synthesis, where solvent properties strongly influence enzyme activity, polymer chain growth, and overall process sustainability. Here, a Design of Experiments (DoE) strategy was employed to systematically investigate the enzymatic synthesis of poly(glycerol adipate) (PGA) using Candida antarctica lipase B (CaLB) across alternative solvent systems. The influence of solvent (2-methyltetrahydrofuran (2-MeTHF), methyl ethyl ketone (MEK), cyclopentyl methyl ether (CPME), and supercritical carbon dioxide (scCO2)), temperature, enzyme loading and reaction time were simultaneously evaluated in the polycondensation of two adipate-based systems − divinyl adipate (DVA) and adipic acid (AA) with glycerol. Across the experimental design space, conversions ranged from 9 to 100 % for DVA and 0–96 % for AA, while the resulting polymers spanned a broad structural range with weight-average molar masses reaching 16300 g/mol and 36700 g/mol for DVA and AA, respectively. Contour plot modelling revealed clear solvent-dependent behaviour, with 2-MeTHF consistently supporting efficient polymerisation, whereas MEK and CPME displayed intermediate performance, and scCO2 exhibited limitations associated with solubility and mass-transfer constraints. The DoE framework enabled the mathematical modelling of solvent effects, providing a predictive strategy for exploring sustainable reaction media while minimizing experimental effort. The results demonstrate how statistically guided experimentation can accelerate the identification of greener reaction media for enzymatic polyester synthesis while enabling rational control over polymer structure.