Synthesis of thermosensitive glycopolymers containing D‐glucose residue: Copolymers with N‐isopropylacrylamide

Abstract

A new glycomonomer, 3-acrylamido-3-deoxy-1,2:5,6-di-O-isopropylidene-a-D-glucofuranose, was synthesized from D-glucose. This monomer was homopolymerized and copolymerized with N-isopropylacrylamide in different compositions by free-radical polymerization. The composition of the copolymer was determined with 1 H-NMR spectroscopy. On acid hydrolysis, water-soluble deprotected copolymers were obtained. The protected and deprotected copolymers showed a sharp cloud-point temperature. A linear correlation was obtained between the lower critical solution temperatures and the concentration of glycomonomer in the copolymers V

Poly(N-isopropylacrylamide)-Based Polymer-Inducing Isothermal Hydrophilic-to-Hydrophobic Phase Transition via Detachment of Hydrophilic Acid-Labile Moiety

“…Triazole containing glycomonomer protected with isopropylidene ketal (TG) and N -(2-(2,4,6-trime-thoxyphenyl)-1,3-dioxan-5-yl)­acrylamide with acetal linkage (TPMDA) are examples of acid-responsive monomers that can be copolymerized with NIPAAm to lower its LCST. The hydrolysis of ketal/acetal linkages and eventual removal of hydrophobic moieties have been shown to induce gradual increase in LCST in a time-dependent manner. − Compared to the aforementioned strategies using detachment of hydrophobic moieties to shift LCST upward, our polymer utilized hydrophilic PMM moieties in which its detachment from the polymer side chain reduced the polymer’s hydrophilicity and subsequently lowered its LCST. P­(NIPAAm/AIPAAm-PMM) also exhibited a sharp phase transition even at pH 6.8, which is higher than the pH required for hydrolysis of ketal (∼pH 2.3) or acetal linkage (∼pH 5.6).…”

“…Hence, tumor-targeted drug delivery using such a polymer design requires gradual cleavage of the hydrophilic moieties. Such temporal control of the cleavage is expected to be achieved by exploiting appropriate linkages, as demonstrated in the previous studies using hydrophobic acid-labile moieties. − Because conventional ionization-dependent LCST polymers exhibit fast protonation and deprotonation, it is difficult to attain the aforementioned functions. Thus, our proposed design offers a useful approach for designing LCST polymers that exerts a hydrophilic-to-hydrophobic phase transition in a spatiotemporally controlled manner in a biological environments.…”

“…Furthermore, excess introduction of the ionizable monomer can reduce or even eliminate phase transition behavior ,,− because the aggregation force of the hydrophobic component in NIPAAm is offset by the increased hydration and disruption of the repetitive structure of the isopropylamide group that captures and releases hydrated water clusters during phase transition. , Considering the above-mentioned limitations, synthesis of a polymer that drastically decreases its LCST in response to narrow pH change without compromising its thermal sensitivity may require new design concept. In this regard, recent studies have proposed ionization-independent LCST polymers exerting a sharp phase transition in response to pH change. − Their proposed polymers were PNIPAAm-based copolymers having hydrophobic moieties in the side chains through acid/base-labile linkers. Acidic or basic condition could induce irreversible detachment of the hydrophobic moieties and eventual isothermal sharp phase transition.…”