Synthesis and UCST-type phase behavior of polypeptide with alkyl side-chains in alcohol or ethanol/water solvent mixtures

A series of thermoresponsive polypeptides bearing 1-butyl, 1-hexyl, or 1-dodecyl side-chains (i.e., 6a - 6c ) were synthesized by copper-mediated 1,3-dipolar cycloaddition with high grafting efficiency (>95%) between side-chain “clickable” polypeptide, namely poly( γ -4-(propargoxycarbonyl)benzyl- L -glutamate) ( 5 ) and 1-azidoalkanes. 5 with different degree of polymerization (DP = 48–86) were prepared from triethylamine initiated ring-opening polymerization of γ -4-(propargoxycarbonyl)benzyl- L -glutamic acid based N -carboxyanhydride ( 4 ). 1 H NMR, FTIR, and GPC results revealed the successful preparation of the resulting polypeptides. 6a - 6c showed reversible UCST-type phase behaviors in methanol, ethanol, and ethanol/water solvent mixtures depending on the polymer main-chain length, alkyl side-chain length, weight percentage of ethanol ( f w ) in the binary solvent, and so forth. FTIR analysis revealed the presence of the van der Waals interaction between the alkyl pendants of polypeptides and alkyl groups of alcoholic solvents. Variable-temperature UV-vis spectroscopy revealed that the UCST-type phase transition temperature ( T pt ) increased as polymer main-chain length or concentration increased. In ethanol/water solvent mixtures, polypeptide with short alkyl pendant (i.e., 1-butyl group) and short main-chain length (DP = 41) showed the widest f w range and T pt s in the range of 61.0–71.1 °C. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54 , 3425–3435