Synthesis and Modeling of Poly(L-lactic acid) via Polycondensation of L-Lactic Acid.

We present synthetic experiments of lactic acid (LA) polycondensation to produce poly(lactic acid) (PLA) as well as kinetic modeling calculations that capture the polymer molecular weight increase with time, given the initial concentrations. Tin-octoate-catalyzed polycondensation of (D,L)- or L-lactic acid was carried out in pre-dried toluene after azeotropic dehydration for 48-120 h at 130-137 °C. The polymerization was optimized by varying lactic acid and catalyst concentrations as well as the temperature. Gel permeation chromatography was used to experimentally follow the evolution of molecular weights and the products were characterized by NMR, TGA, DSC and IR. Under optimal conditions, PLLA with weight-average molecular weight (Mw) of 161 kDa could be obtained. The rate equations that describe polycondensation kinetics were recast in a condensed form that allowed very fast numerical solution and calculation of the number-average molecular weight with time. Deviations with respect to the experiment were minimized in a least-squares fashion to determine rate constants. The optimized kinetics parameters are shown to reproduce the experimental data accurately.

Rapid Oxygen-Tolerant Synthesis of Protein-Polymer Bioconjugates via Aqueous Copper-Mediated Polymerization.

The synthesis of protein-polymer conjugates usually requires extensive and costly deoxygenation procedures, thus limiting their availability and potential applications. In this work, we report the ultrafast synthesis of polymer-protein bioconjugates in the absence of any external deoxygenation via an aqueous copper-mediated methodology. Within 10 min and in the absence of any external stimulus such as light (which may limit the monomer scope and/or disrupt the secondary structure of the protein), a range of hydrophobic and hydrophilic monomers could be successfully grafted from a BSA macroinitiator, yielding well-defined polymer-protein bioconjugates at quantitative yields. Our approach is compatible with a wide range of monomer classes such as (meth) acrylates, styrene, and acrylamides as well as multiple macroinitiators including BSA, BSA nanoparticles, and beta-galactosidase from Aspergillus oryzae. Notably, the synthesis of challenging protein-polymer-polymer triblock copolymers was also demonstrated, thus significantly expanding the scope of our strategy. Importantly, both lower and higher scale polymerizations (from 0.2 to 35 mL) were possible without compromising the overall efficiency and the final yields. This simple methodology paves the way for a plethora of applications in aqueous solutions without the need of external stimuli or tedious deoxygenation.