Rational Design of UCST-type Ureido Copolymers Based on a Hydrophobic Parameter

Abstract

Thermoresponsive polymers exhibiting upper critical solution temperature (UCST)-type behavior under physiologically relevant conditions have potential as biomaterials. The phase separation temperature ( T) of the UCST-type polymers can be increased by copolymerization with hydrophobic comonomers. Quantitative index parameters that could be used to rationally tune the T 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. T 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 T and the hydrophobic parameter, log P, of the acyl groups. Furthermore, the acylation significantly reduced the influence of serum components on T by eliminating interactions of copolymers with serum components such as proteins and lipids. Acylation also abolished pH dependence of T which had been observed for unmodified AM-PU. Owing to the simple relationship between log P and T 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.

Thermoresponsive properties of poly(acrylamide-co-acrylonitrile)-based diblock copolymers synthesized (by PISA) in water

“…They are generally less sensitive to the aforementioned changes. The most studied neutral UCST polymers are N-acryloylglycinamide (NAGA) (co)polymers [22][23][24][25][26][27][28][29] , polymers possessing ureido-moities [30][31][32][33] and (co)polymers based on (meth)acrylamide ((M)AAm) [34][35][36][37][38][39] . Among the latter family, the statistical copolymer poly(acrylamide-co-acrylonitrile) (P(AAm-co-AN)) has gained more and more interest.…”

Unexpected aqueous UCST behavior of a cationic comb polymer with pentaarginine side chains

“…Copolymerization of hydrogen bonding and charged monomers yields to pH-sensitive UCST materials through a delicate balance between electrostatic interactions and hydrogen bonding. Copolymerization of ureido-and allyl-based acrylates allows the rational design of copolymers with a targeted UCST depending on the hydrophobic parameter [19]. Seuring and Agarwal provide guidelines for the design of such copolymers indicating that they should "possess strong hydrogen donors and acceptors, contain no or very few ionic groups, be hydrolytically stable and consist of chains with homogeneous copolymer composition" [9].…”

Evaluation of Cooling‐Induced Liquid–Liquid Phase Separation of Ureido Polymers as a Cold‐Shock Stress Granules Model

“…This implies that the suppressed activity of β‐Gal in the coacervates is due not only to the reduced binding affinity for the substrate but to reduced catalytic activity. The concentration of PAU 5k 92 in the coacervate is at least 40 wt%, [ 23 ] suggesting that the entrapped β‐Gal experiences molecular crowding. Molecular crowding is known to induce structural changes in proteins and nucleic acids.…”