Side chain impacts on pH- and thermo-responsiveness of tertiary amine functionalized polypeptides

The systemic investigation of the structural impacts of side chains on the pH- and thermo-responsiveness of tertiary amine functionalized poly( l -glutamate)s (TA-PGs) was carried out. The TA-PGs polymers were effectively synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition click reaction of azido tertiary amines with poly(γ-propargyl- l -glutamate) (PPLG). Turbimetric measurements were performed to characterize the pH- and temperature-induced phase transition of TA-PGs in aqueous solution, which suggested a structural dependence of the properties on the N -substituted groups and the “linkers” between 1,2,3-triazole ring and the tertiary amine groups in the side chains. In detail, the pH responsive properties of TA-PGs were basically determined by the hydrophobicity of the N -substituted groups in the side chains and the pH transition point (pH t ) decreased as the increasing hydrophobicity of the N -substituted groups, while the temperature-responsiveness of TA-PGs were affected by either the N -substituted groups or the “linkers.” TA-PGs with a moderate N -substituted amine group (e.g., DEA, PR, and PD) or a branched “linker” (e.g., iso -propylene and 2-methylpropylene group) were more likely to express the LCST-type phase transition tuned by pH variation. These structure–property relationships revealed in this study would help to develop the applications of TA-PGs in smart drug delivery systems. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52 , 671–679