LCST/UCST-type thermosensitive properties of carboxy-terminal PAMAM dendrimers modified with different numbers of phenylalanine residues

Stimuli-sensitive polymers are useful smart materials. Dendrimers are synthetic polymers with well-defined structures, and various functional dendrimers have been produced by modifying compounds at their termini. We previously reported that polyamidoamine (PAMAM) dendrimers modified with cis-1,2-cyclohexane dicarboxylic acid (CHex) and phenylalanine (Phe), named PAMAM-CHex-Phe, exhibit upper critical solution temperature (UCST)-type thermosensitivity at acidic pH. In this study, we synthesized PAMAM dendrimers with CHex and various numbers of bound Phe residues and examined their pH and temperature sensitivities. Interestingly, PAMAM-CHex-Phe, with fewer than 32 Phe residues, showed lower critical solution temperature (LCST)-type thermosensitivity at pH 5 but not UCST-type thermosensitivity. PAMAM-CHex-Phe40 and PAMAM-CHex-Phe48 exhibited both LCST- and UCST-type thermosensitivity at pH values of 5 and 6, respectively. Fully Phe-modified PAMAM-CHex-Phe (PAMAM-CHex-Phe64) showed UCST-type but not LCST-type thermosensitivity. pH titration experiments suggested that the protonation behaviors of these dendrimers were different, likely resulting in different phase transitions. Therefore, the phase transition temperature and behavior could be regulated by varying the number of bound Phe residues in the PAMAM-CHex-Phe dendrimers and the solution pH.