Synthesis and UCST-type phase behavior of OEGylated poly(γ-benzyl-l-glutamate) in organic media

Abstract

A series of OEGylated poly(c-benzyl-L-glutamate) with different oligo-ethylene-glycol side-chain length, molecular weight (MW 5 8.4 3 10 3 to 13.5 3 10 4 ) and narrow molecular weight distribution (PDI 5 1.12-1.19) can be readily prepared from triethylamine initiated ring-opening polymerization of OEGylated c-benzyl-L-glutamic acid based N-carboxyanhydride. FTIR analysis revealed that the polymers adopted a-helical conformation in the solid-state. While they showed poor solubility in water, they exhibited a reversible upper critical solution temperature (UCST)-type phase behavior in various alcoholic organic solvents (i.e., methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, and isopropanol). Variable-temperature UV-vis analysis revealed that the UCST-type transition temperatures (T pt s) of the resulting polymers were highly dependent on the type of solvent, polymer concentration, side-and main-chain length.

Synthesis and UCST-type phase behavior of polypeptide with alkyl side-chains in alcohol or ethanol/water solvent mixtures

“…They can be prepared in large‐scale by ring‐opening polymerization (ROP) from N ‐carboxyanhydride (NCA) monomers . While significant progress has been made on stimuli‐responsive polypeptides, UCST‐type thermoresponsive polypeptides in organic media has been less investigated . Moreover, UCST‐type phase behaviors of polypeptide in a binary solvent mixture have never been reported yet.…”

Synthesis and UCST-type phase behaviors of OEGylated random copolypeptides in alcoholic solvents

“…OEGylated random copolypeptides, namely, poly( γ −4‐oligo(ethylene glycol)benzyl‐ L ‐glutamate)‐ random ‐poly( γ ‐benzyl‐ L ‐glutamate) (POEG m BLG‐ ran ‐PBLG, m = 2, 3), were synthesized by ring‐opening polymerization of γ −4‐oligo(ethylene glycol)benzyl‐ L ‐glutamic acid based N ‐carboxyanhydride (OEG m BLG–NCA, m = 2, 3) and γ ‐benzyl‐ L ‐glutamic acid based N ‐carboxyanhydride (BLG–NCA) at room temperature using anhydrous DMF as the solvent and triethylamine (Et 3 N) as the initiator (Scheme ). The NCA monomers were prepared according to reported procedures . In order to obtain copolypeptide samples with constant main‐chain lengths and different content of oligo(ethylene glycol) (OEG) pendants, the initial monomer to initiator ratio was fixed while the feeding composition of OEG m BLG–NCA and BLG–NCA was adjusted as designed.…”

“…Methanol (MeOH, 99.8%) and all other chemicals were purchased from Tianjin HengXing Chemical Reagent. γ −4‐Oligo(ethylene glycol)benzyl‐ L ‐glutamic acid based N ‐carboxyanhydride (OEG m BLG–NCA, m = 2, 3) and γ ‐benzyl‐ L ‐glutamic acid based N ‐carboxyanhydride (BLG–NCA) were synthesized by reported procedures . Deionized water (DI H 2 O) was obtained from Aquapro AR1‐100L‐P11 water‐purification system (Ever Young Enterprises Development, People's Republic of China).…”

“…Recently, stimuli‐responsive polypeptides with responsiveness to pH, temperature, light, oxidation, and gas have gained increased attention for their great potential as smart biomaterials . While thermoresponsive polypeptides with LCSTs have been intensively studied, thermoresponsive polypeptides with UCSTs have been less investigated . For example, polypeptides with ionic liquid pendants (e.g., imidazolium or pyridinium) showed UCST‐type phase behaviors in aqueous solutions.…”

“…For example, polypeptides with ionic liquid pendants (e.g., imidazolium or pyridinium) showed UCST‐type phase behaviors in aqueous solutions. OEGylated homopolypeptides showed UCST‐type phase behaviors in water, methanol, and ethanol depending on the main‐chain and side‐chain lengths . To enrich the number of thermoresponsive polypeptides with UCSTs in organic media and expand our understanding of their structure–property relationships, synthesis and investigation of thermoresponsive random copolypeptides provide a practical and feasible way.…”