Rational Guidelines for the Two‐Step Scalability of Enzymatic Polycondensation: Experimental and Computational Optimization of the Enzymatic Synthesis of Poly(glycerolazelate)

Abstract

The lipase‐catalyzed polycondensation of azelaic acid and glycerol is investigated according to a Design‐of‐Experiment approach that helps to elucidate the effect of experimental variables on monomer conversion, Mn and regioselectivity of acylation of glycerol. Chemometric analysis shows that after 24 h the reaction proceeds regardless of the presence of the enzyme. Accordingly, the biocatalyst was removed after a first step of synthesis and the chain elongation continued at 80 °C. That allowed the removal of the biocatalyst and the preservation of its activity: pre‐requites for efficient applicability at industrial scale. The experimental study, combined with docking‐based computational analysis, provides rational guidelines for the optimization of the regioselective acylation of glycerol. The process is scaled up to 73.5 g of monomer. The novelty of the present study is the rigorous control of the reaction conditions and of the integrity of the immobilized biocatalyst, which serve to avoiding any interference of free enzyme or fines released in the reaction mixture. The quantitative analysis of the effect of experimental conditions and the overcoming of some major technical bottlenecks for the scalability of enzymatic polycondensation opens new scenarios for industrial exploitation.

Understanding Marine Biodegradation of Bio-Based Oligoesters and Plasticizers

“…The bio-based oligoesters poly(butyleneadipate) and poly(glycerolazelate) were investigated to understand some of the drivers of marine biodegradation in bio-based polyesters, which are not natural polymers but are obtainable through the enzyme-catalyzed synthesis of ester bonds connecting the bio-based monomers. The use of a lipase as a catalyst allowed for the control of the molecular weight and the structure of the products—for instance, avoiding branching [ 27 ].…”

“…Lipase B from Candida antarctica (CaLB) was employed for catalyzing the polycondensation of adipic acid and 1,4-BDO to obtain poly(butyleneadipate) (BDO-AA), as well as that of azelaic acid and glycerol to yield poly(glycerolazelate) (Gly-AZA), exploiting the specificity of CalB for the primary hydroxyl groups [ 28 ]. The process was carried out at 70 °C under solventless conditions and using a thin-film system, as previously described by Todea et al [ 27 ].…”

“…These oligoesters were selected not only for their potential industrial relevance, but also because they have already been the object of extensive investigations concerning their synthesis, structural properties, and degradation. Previously, we have reported the synthesis of oligoesters of poly(glycerolazelate) [ 27 ] for potential use in dermatological and cosmetic formulations, due to the pharmacological properties of azelaic acid [ 29 ]. Therefore, these oligoesters are subjected to be washed off and collected in the wastewater, ultimately reaching the sea.…”

“…Notably, previous computational simulations shed light on the ability of different hydrolases to recognize poly(glycerolazelate) as a substrate in both synthetic and hydrolytic reactions [ 27 ]. As the synthesis of the ester bond is a reversible reaction, these oligoesters can in principle undergo hydrolytic degradation catalyzed by the same enzymes used for their synthesis—namely, triacylglycerol hydrolases, which are quite ubiquitous in nature.…”

“…Marine water is typically slightly alkaline (pH = 8.1), so biodegradation of chemicals that occur more frequently in slightly acidic or neutral environments—such as esters and polyesters—is disadvantaged under such conditions, as they could induce a lack of the microbial strains needed in the marine medium to support effective biodegradation [ 51 ]. Notably, we have already demonstrated the lability of the ester between glycerol and azelaic acid that simulated the physiological skin environment at pH 4.5 [ 27 ].…”