Degradable polymers with adjustable thermoresponsiveness based on multicomponent polymerization and molecular recognition

Abstract

Thermoresponsive polymers with lower critical solution temperature have attracted intensive attention due to their wide range of applications as smart materials. Their thermoresponsive behaviors are influenced by the balance between the hydrophobic and hydrophilic moieties present in the polymers. In this research, Passerini multicomponent polymerization of benzaldehyde group-modified poly(ethylene glycol) (PEG) (M_n = 600, 1000, 1500, 2000, or 4000 Da), 3,3′-dithiodipropionic acid, and 1-isocyanoadamantane is conducted to prepare degradable polymers P(PEG) with adjustable thermoresponsiveness. The fractionation of P(PEG) was carried out to obtain fractions with low dispersities. In P(PEG), the balance between the hydrophilic PEG segments and the hydrophobic diethyl disulfide and adamantyl groups greatly affects the dissolution and thermoresponsive behaviors of P(PEG). It was discovered that P(PEG600) and P(PEG1000) were insoluble, while P(PEG1500), P(PEG4000), and most fractions of P(PEG2000) were thermoresponsive with cloud point temperatures (T_cp) ranging from 24.8 to 60.8 °C. The T_cp of P(PEG) increases with increasing M_n of the PEG precursor but decreases with increasing M_n of P(PEG). The Hofmeister effect of the thermoresponsive P(PEG) was investigated using the fraction P(PEG1500)-1 whose T_cp was close to that of poly(N-isopropyl acrylamide). It was found that P(PEG1500)-1 followed the Hofmeister series and exhibited high sensitivity to anions, which is attributed to the high sensitivity of PEG and the alternating structure of hydrophilic and hydrophobic moieties. Based on the molecular recognition between the adamantyl groups of P(PEG) and β-cyclodextrin (β-CD) derivatives, the aqueous solubility and T_cp of P(PEG) could be adjusted. Due to the dynamic interaction of the molecular recognition, P(PEG) could be successively modified with several β-CD derivatives, offering facile control of the T_cp and the zeta potential of the polymer. All the P(PEG) could be degraded in DMF through the cleavage of the disulfide linkages. In water, the assemblies of P(PEG) could also be degraded into about 10 nm fragments when mixed with 10 mM glutathione solution. This degradable PEG-based polymer with adjustable thermoresponsiveness can be applied as a new smart material.