Integrating Computational and Experimental Methods for the Rational Ecodesign and Synthesis of Functionalized Safe...

A chemical platform for post-polymerization methods was developed, starting from the ecodesign and enzymatic synthesis of safe and sustainable bio-based polyesters containing discrete units of itaconic acid. This unsaturated bio-based monomer enables the covalent linkage of molecules that can impart desired properties such as hydrophilicity, flexibility, permeability, or affinity for biological targets. Molecular descriptor-based computational methods, which are generally used for modeling the pharmacokinetic properties of drugs (ADME), were employed to predict in silico the hydrophobicity (LogP), permeability, and flexibility of virtual terpolymers composed of different polyols (1,4-butanediol, glycerol, 1,3-propanediol, and 1,2-ethanediol) with adipic acid and itaconic acid. Itaconic acid, with its reactive vinyl group, acts as a chemical platform for various post-polymerization functionalizations. Poly(glycerol adipate itaconate) was selected because of its higher hydrophilicity and synthetized via solvent-free enzymatic polycondensation at 50 °C to prevent the isomerization or crosslinking of itaconic acid. The ecotoxicity and marine biodegradability of the resulting oligoester were assessed experimentally in order to verify its compliance with safety and sustainability criteria. Finally, the viability of the covalent linkage of biomolecules via Michael addition to the vinyl pendant of the oligoesters was verified using four molecules bearing thiol and amine nucleophilic groups: N-acetylcysteine, N-Ac-Phe-ε-Lys-OtBu, Lys-Lys-Lys, and glucosamine.