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

Abstract

Thermoresponsive polypeptides bearing oligo(ethylene glycol) (OEG) pendants (i.e., P1‐OEGx and P2‐OEGx, x = 3, 7) were synthesized by copper‐mediated 1,3‐dipolar cycloaddition with high grafting efficiency (≥97%) between side‐chain “clickable” polypeptides, namely poly(γ‐4‐(propargoxycarbonyl)benzyl‐l‐glutamate) (P1) or poly(γ‐4‐(4‐propargoxyphenoxycarbonyl)benzyl‐l‐glutamate) (P2) and azido functionalized OEG (N3‐OEGx). P1 and P2 with similar degree of polymerization (DP = 35 or 37) were prepared from triethylamine initiated ring‐opening polymerization of respective N‐carboxyanhydrides. P1‐OEGx (x = 3, 7) and P2‐OEG7 showed reversible UCST‐type phase transitions in various alcoholic solvents (e.g., ethanol, propanol, n‐butanol, and n‐pentanol). P2‐OEG3 also showed reversible UCST‐type phase transitions in ethanol/water solvent mixtures at the weight percentage of ethanol no less than 50 wt %. P1‐OEG7 and P2‐OEG7 showed reversible LCST‐type phase transitions in aqueous solutions. Variable‐temperature UV–vis spectroscopy revealed that the LCST‐type phase transition temperature (Tpt) of P2‐OEG7 with benzoic acid phenyl ester linkages was at around body temperature and it was barely changed with the variation of polymer concentration, yet it showed noticeable dependence on the nature of salt (i.e., NaCl, NaBr, NaI, or KCl) and salt concentration in the range of 0–300 mM. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 163–173

Core–Shell Copolymers with Brush-on-Hyperbranched Arm Architecture: Synthesis, Dual Thermoresponsive Behaviors, and Nanocarriers

“…The influence of polymer concentration on the LCST has been extensively explored, and the trend observed in the current study agreed with those from the literature. ,, It could be attributed to the enhanced intermolecular aggregation with increasing concentration. However, much less attention has been given to the influence of molecular architecture on LCST behaviors. ,, Considering that the LCST of PEG chains in aqueous solutions is usually attributed to the thermodissociation of hydrogen bonds between the oxygen atoms in the ethylene glycol unit and water molecules upon heating, , plausible reasons could be raised for the molecular architecture-dependent LCST behaviors. When the molecular weight of PEG chains increased, the overall hydrogen bonding interaction strength between the copolymer and surrounding water molecules increased, requiring a higher temperature to break the hydrogen bonding interaction. ,, Similarly, longer GAP arms on the copolymers also led to enhanced hydrogen bonding interactions, resulting in a higher CP. , Meanwhile, despite the same PEG chain length, without the high grafting density, the linear PEG- g -GAP-10 brushes or PEG homopolymers could not show LCST behaviors due to their much higher configurational entropy and, thus, higher solubility in water.…”

“…As shown in Figure b, the transmittance of the solutions of PEG 1900 - g -POG-8 changed from 100% to almost 0% when the solution was cooled below 15 °C. The CP was also defined as where the transmittance decreased by 50% of the difference from the initial value to the final value, , as indicated in Figure b. Therefore, when the concentration was fixed to 5.0 mg·mL –1 , the CP for the THF solutions of PEG 1900 - g -POG-8 was determined to be 14.5 °C, while PEG 350 - g -POG-8 and PEG 750 - g -POG-8 showed no UCST behavior, as shown in Figure b.…”

“…However, much less attention has been given to the influence of molecular architecture on LCST behaviors. 62,68,69 Considering that the LCST of PEG chains in aqueous solutions is usually attributed to the thermodissociation of hydrogen bonds between the oxygen atoms in the ethylene glycol unit and water molecules upon heating, 66,70 plausible reasons could be raised for the molecular architecture-dependent LCST behaviors. When the molecular weight of PEG chains increased, the overall hydrogen bonding interaction strength between the copolymer and surrounding water molecules increased, requiring a higher temperature to break the hydrogen bonding interaction.…”

“…When the molecular weight of PEG chains increased, the overall hydrogen bonding interaction strength between the copolymer and surrounding water molecules increased, requiring a higher temperature to break the hydrogen bonding interaction. 59,70,71 Similarly, longer GAP arms on the copolymers also led to enhanced hydrogen bonding interactions, resulting in a higher CP. 72,73 Meanwhile, despite the same PEG chain length, without the high grafting density, the linear PEG-g-GAP-10 brushes or PEG homopolymers could not show LCST behaviors due to their much higher configurational entropy and, thus, higher solubility in water.…”

Synthesis of novel 1,5 bis-propargyloxy-sulfides via β, β’-dihydroxythioethers derived from epoxides

“…Synthetic methods of organic chemistry demonstrate alkyne groups to be most reactive ones which increase the importance of the compound 17 . Low cost, high yield of the compound has attracted the attention of scientists to synthesize the compound as monomer for many polymeric compounds 18,19 . They are used as an intermediate for the synthesis of triazole by the click chemistry 20,21 .…”