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Gaining understanding on the aggregation behavior of proteins under concentrated conditions is of both fundamental and industrial relevance. Here, we study the aggregation kinetics of a model monoclonal antibody (mAb) under thermal stress over a wide range of protein concentrations in various buffer solutions. We follow experimentally the monomer depletion and the aggregate growth by size exclusion chromatography with inline light scattering. We describe the experimental results in the frame of a kinetic model based on population balance equations, which allows one to discriminate the contributions of the conformational and of the colloidal stabilities to the global aggregation rate. Finally, we propose an expression for the aggregation rate constant, which accounts for solution viscosity, protein-protein interactions, as well as aggregate compactness. All these effects can be quantified by light scattering techniques. It is found that the model describes well the experimental data under dilute conditions. Under concentrated conditions, good model predictions are obtained when the solution pH is far below the isoelectric point (pI) of the mAb. However, peculiar effects arise when the solution pH is increased toward the mAb pI, and possible explanations are discussed.

A new synthetic pathway for the polymerization of furan based polyesters is reported in this work. First, poly(butylene 2,5-furandicarboxylate) cyclic oligoesters (COEs) are chemically synthesized by semi-batch esterifi cation. The structure of the COEs is confi rmed by infrared spectroscopy, 1 H, and 13 C-NMR, while the molecular weight distribution of the COEs is determined by matrix-assisted laser desorption/ionization time of fl ight mass spectroscopy. The cyclic oligoesters are then successfully polymerized via ring-opening polymerization using tetrakis(2ethylhexyl)-titanate as catalyst. Differential scanning calorimetry and 1 H-NMR analysis unambiguously proves the formation of polymeric species. Both end-group analysis from 1 H-NMR spectrum and calculation through Flory-Fox equation give comparable estimates of the number average molecular weight: 5.8 × 10 3 g mol −1 and 7.8 × 10 3 g mol −1 , respectively. this approach. A still unexplored alternative route to produce this class of macromolecules consists in performing a ring-opening polymerization (ROP), exploiting the benefi ts of a living polymerization mechanism to overcome the typical polycondensation limits. In addition, the ROP method would enable a more precise control of the molecular weight and structure of the synthesized polymer and therefore of the material properties. [ 22,23 ] A ROP strategy is applied for the very fi rst time to the polymerization of furan based polymers. To pursue this strategy, a viable synthesis of the cyclic precursors must be envisioned and developed, and the ring-opening polymerization of these latter has to be proved. In short, the aim of this work is to explore the possibility to apply to furan-based polyesters a synthetic pathway similar to the one successfully developed for the production of polylactic acid, which is actually well-established also at industrial scale. [ 24,25 ] Accordingly, herein we present for the fi rst time the chemical synthesis of cyclic oligomers of butylene-2,5-furandicarboxylate and their successful polymerization into polybutylene 2,5-furanoate (PBF) by ROP. The proposed synthetic pathway could be generalized in the future to other furan-based copolymers, such as D. Pfi ster et al.

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