Synthesis And Thermoresponsive Properties Of Ionic Poly(L-glutamate)

Thermoresponsive polymers are an important type of smart polymers with great potential applications as biomedical materials. However, most thermoresponsive polymers are derivatized from non-biodegradable polyacrylates or polyacrylamides, which restricted their use in biomedical applications. Recently, thermoresponsive polypeptides have gained significant attention due to their promising properties including biocompatibility and unique secondary conformations. In this dissertation, we have designed and synthesized a series of poly(L-glutamate)s bearing imidazolium groups, among which we discovered the first example of ionic and α-helical polypeptides with an upper critical solution temperature(UCST) in water. We have systematic investigated the structure-property relationship, and the effect of concentration and ionic strength on the thermoresponsive properties. The polymers we made will enrich the variety of thermoresponsive polypeptide. Our results not only shed some light on the mechanism of solution phase transitions, but also provide guidence for future molecular design on other thermoresponsive polymers. Details are as follows:γ-4-(3-Chloropropoxycarbonyl)benzyl-L-glutamate based N-carboxyanhydirde(NCA) and γ-4-chloromethylbenzyl-L-glutamate based N-carboxyanhydirde were synthesized by monoesterifications and cyclization in the presence of triphosgene in anhydrous THF from γ-4-(3-chloropropoxy-carbonyl)benzyl-L-glutamate and γ-4-chloromethylbenzyl-L-glutamate. Two types of polypeptides with different spacer lengths, namely poly(γ-4-(3-chloropropoxycarbonyl)benzyl-L-glutamate) and poly(γ-4-chloromethylbenzyl-L-glutamate) were prepared via the ring-opening polymerization(ROP) of respective NCAs. Water-soluble ionic polypeptides bearing 1-butylimidazolium and various counter-anions(i.e., Cl–, I– or BF4–) were prepared by nuleophilic substitution and ion-exchange reaction.CD analysis revealed that the resulting ionic polypeptides adopted α-helical conformation in water and exhibited good conformational stability against temperature variations(20-80 °C). Some polypeptides exhibited lower critical solution temperature(LCST)-type or UCST-type transitions in organic solvents. For example, polypeptides with I– counter-anions showed UCST-tye transitions in ethanol while polypeptides with BF4– counter-anions prepared from poly(γ-4-chloromethylbenzyl-L-glutamate) showed LCST-type transitions in acetone.Polypeptides with I– or BF4– counter-anions showed UCST-type transitions in water. The UCST-type transition temperature(Tpt) in water was independent on the molecular weight, yet it was very dependent on the counter-anions, spacer length, concentration, and salt. The Tpt increased as increasing the spacer length and polymer concentration. Additionally, the Tpt increased as increasing the concentration of Na I or Na BF4, but it decreased as increasing the concentration of Na Cl.