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

Abstract

A series of thermoresponsive polypeptides bearing 1‐butyl, 1‐hexyl, or 1‐dodecyl side‐chains (i.e., 6a‐6c) were synthesized by copper‐mediated 1,3‐dipolar cycloaddition with high grafting efficiency (>95%) between side‐chain “clickable” polypeptide, namely poly(γ‐4‐(propargoxycarbonyl)benzyl‐L‐glutamate) (5) and 1‐azidoalkanes. 5 with different degree of polymerization (DP = 48–86) were prepared from triethylamine initiated ring‐opening polymerization of γ‐4‐(propargoxycarbonyl)benzyl‐L‐glutamic acid based N‐carboxyanhydride (4). 1H NMR, FTIR, and GPC results revealed the successful preparation of the resulting polypeptides. 6a‐6c showed reversible UCST‐type phase behaviors in methanol, ethanol, and ethanol/water solvent mixtures depending on the polymer main‐chain length, alkyl side‐chain length, weight percentage of ethanol (fw) in the binary solvent, and so forth. FTIR analysis revealed the presence of the van der Waals interaction between the alkyl pendants of polypeptides and alkyl groups of alcoholic solvents. Variable‐temperature UV‐vis spectroscopy revealed that the UCST‐type phase transition temperature (Tpt) increased as polymer main‐chain length or concentration increased. In ethanol/water solvent mixtures, polypeptide with short alkyl pendant (i.e., 1‐butyl group) and short main‐chain length (DP = 41) showed the widest fw range and Tpts in the range of 61.0–71.1 °C. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3425–3435

Synthesis and thermoresponsive properties of OEGylated polypeptide with a LCST at body temperature in water and with a UCST in alcohol or ethanol/water solvent mixture

“…OEGylated polypeptides (P1‐OEG x and P2‐OEG x , x = 3, 7) with different hydrophobic linkage groups (phenyl linkage for P1‐OEG x and benzoic acid phenyl ester linkage for P2‐OEG x ) and various OEG pendants were designed to achieve thermoresponsive polypeptides with a lower critical solution temperature (LCST)‐type solution phase transition temperature ( T pt ) at around body temperature. P1 (Scheme ) was prepared according to a reported procedure using Et 3 N as the initiator . The molecular structures of the monomer and P1 were confirmed by 1 H NMR spectroscopy (Supporting Information Fig.…”

“…The solubility difference in MeOH for P1‐OEG 7 and P2‐OEG 7 was ascribed to the hydrophobicity increase in P2‐OEG 7 . The mechanism of UCST‐type solution phase transition in alcohols is that polymers tend to aggregated at low temperatures, but H‐bonding interactions between the polar linkages (e.g., ester bonds and 1,2,3‐triazole groups) and OEG groups of polymers and alcoholic molecules increased as temperature elevation, resulting in polymer dissolution …”

“…Moreover, ethanol/water solvent mixtures are of low toxicity, which makes this system promising for application in personal care or medical pharmaceutical areas . Previous work have suggested that thermoresponsive polymers with UCST‐type phase behaviors in alcoholic solvents also showed UCST‐type phase behaviors in ethanol/water binary solvent mixtures . Therefore, the solution properties of P1‐OEG x and P2‐OEG x ( x = 3, 7) have also been investigated (Supporting Information Table S1).…”

“…Poly( γ ‐4‐(propargoxycarbonyl)benzyl‐ l ‐glutamate) (P1), azido functionalized triethylene glycol monomethylether (N 3 ‐OEG 3 ) and azido functionalized poly(ethylene glycol) methyl ether 350 (N 3 ‐OEG 7 ), l ‐glutamic acid copper salt were prepared by reported procedures. 4‐(Chloromethyl)benzoyl chloride (98%), triphosgene (98%), p ‐toluenesulfonyl chloride (98%), N , N , N ′, N ′‐tetramethylguanidine (TMG, 98%), propargyl bromide (99%), copper bromide (CuBr, 99%), N , N , N ′, N ″, N ″‐pentamethyldiethylenetriamine (PMDETA, 99%), NaI (98%), and trifluoroacetic acid (99%) were purchased from Energy Chemical.…”

Preparation and Thermoresponsive Properties of UCST‐Type Polypeptide Bearing p‐Tolyl Pendants and 3‐Methyl‐1,2,3‐triazolium Linkages in Methanol or Ethanol/Water Solvent Mixtures

“…Previous work have suggested that thermoresponsive polymers with UCST‐type phase behaviors in alcoholic solvents also showed UCST‐type phase behaviors in alcohol/water binary solvent mixtures . Therefore, the solubility of the resulting polypeptides in MeOH/H 2 O or EtOH/H 2 O binary solvent mixtures has also been tested.…”