Rational Design of UCST-type Ureido Copolymers Based on a Hydrophobic Parameter.
Thermoresponsive polymers exhibiting upper critical solution temperature (UCST)-type behavior under physiologically relevant conditions have potential as biomaterials. The phase separation temperature ( Tp) of the UCST-type polymers can be increased by copolymerization with hydrophobic comonomers. Quantitative index parameters that could be used to rationally tune the Tp are lacking, however. We have reported that ureido copolymers such as poly(allylamine- co-allylurea) (AM-PU) and poly(l-ornithine- co-citrulline) exhibit UCST-type solution behavior under physiologically relevant conditions. In this study, AM-PU was hydrophobized by acylation. Tp of AM-PU can be regulated in a wide temperature range from about 20 to 80 °C or even higher by 20 mol % acylation with acetyl, propionyl, isobutanoyl, or pivaloyl groups, implying considerable impacts of hydrophobic groups on UCST phase separation. We observed a liner relationship between Tp and the hydrophobic parameter, log P, of the acyl groups. Furthermore, the acylation significantly reduced the influence of serum components on Tp by eliminating interactions of copolymers with serum components such as proteins and lipids. Acylation also abolished pH dependence of Tp which had been observed for unmodified AM-PU. Owing to the simple relationship between log P and Tp and the inertness of the acylated copolymer to serum components and pH changes, it is possible to rationally design copolymers exhibiting UCST-type behavior at a desired temperature under biological conditions.