Side-chain functionality driven thermoresponsive and semicrystalline poly(L-glutamate)s and self-assembly

Abstract

The appropriate functionalization of synthetic polypeptides is the key to introduce stimuli-responsiveness and amphiphilicity for generating self-assembled nanostructures (micelles, vesicles, etc.) with promising applications in the areas of drug/gene delivery and tissue engineering. This work presents a way to functionalize poly(L-glutamate)s with long chain alkyl groups and to study the semicrystalline as well as solution-phase behavior such as thermoresponsiveness, self-aggregation etc. of the resultant polypeptides. The ring opening polymerization (ROP) of the as-synthesized γ-propargyl-L-glutamate N-carboxyanhydride produce poly(L-glutamate) (PGlu-Pr) with pendant propargyl group, which is clicked with long-chain alkyl azides via Cu-catalyzed alkyne-azide-cycloaddition (Cu-AAC) reaction to give alkyl-grafted poly(L-glutamate)s [PGlu–Cn(s), n = 10, 12, 16, 20]. The helical secondary conformation predominates for PGlu-Pr and PGlu–Cn(s) in both solution phase and in solid state and the extent of helicity decreases with increase in the length of alkyl chains. The corresponding control monomeric analogs, alkyl grafted L-glutamates (Glu–Cn)s, show formation of birefringent crystals due to the presence of the long alkyl chains as examined by differential scanning calorimetry (DSC) and polarized optical microscopy. Whereas PGlu–Cn(s) having n ≥ 12 show feeble crystallinity in their solid state. Interestingly, the solutions of PGlu–Cn(s) in CHCl3 and THF show upper critical solution temperature (UCST)-type thermoresponsive properties with tunable cloud point, but no such property is observed for Glu–Cn(s). Self-assembly of PGlu–Cn(s) in these solvents generates vesicular nanoaggregates as confirmed by the dynamic light scattering and transmission electron microscopy. These nanoaggregates can encapsulate organic dye (Eosin B) as studied by fluorescence and confocal microscopy.