Preparation and properties of thermo- and pH-responsive polypeptide bearing OEG and aldehyde pendants

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Preparation and properties of thermo- and pH-responsive polypeptide bearing OEG and aldehyde pendants Congping Zhou 1 & Zuowen Shi 1 & Fei Xu 1 & Ying Ling 1 & Haoyu Tang 1 Received: 20 December 2019 / Accepted: 18 July 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract OEGylated polypeptide bearing triethylene glycol monomethylether (OEG3) and poly(ethylene glycol) methyl ether 350 (OEG7) were first prepared by copper-mediated 1,3-dipolar cycloaddition. 1H NMR, FTIR, and GPC results indicated the successful conjugation of oligo(ethylene glycol) (OEG) pendants with high grafting efficiency (≥ 98%). Variable temperature UV–vis spectroscopy revealed a reversible lower critical solution temperature (LCST)-type phase transition of the resulting polypeptides. The LCST-type cloud point temperature (Tcp) in the range of 20–60 °C can be readily tuned by changing the OEG3 and OEG7 composition. Thermo- and pH-responsive polypeptide was prepared by first conjugating of OEG and 6-aldehyde hexyl pendants, then crosslinking in the presence of 1,6-hexanediamine, yielding OEGylated polypeptide bearing pH-labile imine bonds. The resulting polypeptide showed pH-responsive property and less pronounced thermoresponsive property at high pH values (i.e., ≥ 6.15) and noticeable thermo- and pH- dual responsive properties at low pH values (i.e., ≤ 5.80). Keywords Stimuli-responsive polymers . Thermoresponsive property . pH-responsive property . Lower critical solution temperature . Cloud point temperatures

Introduction Stimuli-responsive polymers can undergo chemical or physical changes on receiving external triggers, leading to interesting property variations, such as solubility, permeability, mechanical and optical properties, and bioactivity. [1] They have gained significant attention for their potential applications ranging from nanotechnology to biomaterials. [2–5] Among all stimuli-responsive polymers, thermo- and pH-responsive polymers are the most studied because temperature and pH are the most common environment stimulators. [6–12] Usually, thermoresponsive polymers undergo a solution phase separation upon heating or cooling, corresponding to the polymers with a lower critical solution temperature (LCST) or an upper critical solution temperature (UCST). [13–18] The cloud point * Ying Ling [email protected] * Haoyu Tang [email protected] 1

Key Laboratory of Polymeric Materials and Application Technology of Hunan Province, College of Chemistry, Xiangtan University, Xiangtan 411105, Hunan, China

temperature (Tcp) is an important parameter to evaluate the property of thermoresponsive polymers. A tunable Tcp can be readily achieved by adjusting the hydrophilic/ hydrophobic balance of polymer structures, which is critical to various practical applications. [19–28] On the other hand, pH-responsive polymers can undergo structural and property changes upon pH variations. [29–31] They can be constructed by incorporation of acidic (e.g., carboxylic groups), basic groups (e.g., amino gro