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(gamma-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 gamma-4-(propargoxycarbonyl) benzyl-L-glutamic acid based N-carboxyanhydride (4). H-1 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 polymermain-chain length, alkyl side-chain length, weight percentage of ethanol (f(vv)) 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 shortmain-chain length (DP=41) showed the widest f(vv) range and T(pt)s in the range of 61.0-71.1 degrees C. (C) 2016 Wiley Periodicals, Inc.