Thermo-reversible supramolecular hydrogels of trehalose-type diblock methylcellulose analogues

Abstract

This paper describes the design and synthesis of new trehalose-type diblock methylcellulose analogues with nonionic, cationic, and anionic cellobiosyl segments, namely 1-(tri-O-methyl-cellulosyl)-4-[β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyloxymethyl]-1H-1,2,3-triazole (1), 1-(tri-O-methyl-cellulosyl)-4-[(6-amino-6-deoxy-β-d-glucopyranosyl)-(1→4)- 6-amino-6-deoxy-β-d-glucopyranosyloxymethyl]-1H-1,2,3-triazole (2), and 4-(tri-O-methyl-cellulosyloxymethyl)-1-[β-d-glucopyranuronosyl-(1→4)-β-d-glucopyranuronosyl]-1H-1,2,3-triazole (3), respectively. Aqueous solutions of all of the 1,2,3-triazole-linked diblock methylcellulose analogues possessed higher surface activities than that of industrially produced methylcellulose and exhibited lower critical solution temperatures, that allowed the formation of thermoresponsive supramolecular hydrogels at close to human body temperature. Supramolecular structures of thermo-reversible hydrogels based on compounds 1, 2, and 3 were investigated by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Detailed structure-property-function relationships of compounds 1, 2, and 3 were discussed. Not only nonionic hydrophilic segment but also ionic hydrophilic segments of diblock methylcellulose analogues were valid for the formation of thermo-reversible supramolecular hydrogels based on end-functionalized methylcellulose.

Methylcelluloses end-functionalized with peptides as thermoresponsive supramolecular hydrogelators

“…The triazole proton of compound 4b appears at 7.69 (β-anomer) and 7.70 (αanomer) ppm (α/β ratio = 2/1) (Yamagami et al 2018), while the triazole protons of compounds 5b and 6b were unable to be identified due to overlapping resonances associated with the aromatic protons of their Fmoc groups, although proton resonances of the peptide side-chains were observed.…”

“…Scheme displays the synthetic routes to methylcelluloses end-functionalized with peptides, as well as the control compounds. Trehalose-type methylated cellobiose derivative 1a and diblock methylcellulose analogues 1b (Yamagami et al 2018) are control compounds for peptide-functionalized methylated cellobiose derivatives 2a and 3a, and peptide-end-functionalized methylcelluloses 2b and 3b, respectively. Carbon resonances of compounds 1a, 2a, and 3a have also been assigned (see experimental section).…”

“…Hence, the reaction conditions developed for these cellobiose derivatives were used to synthesize the peptide-functionalized methylcelluloses 1b, 2b, and 3b. Compounds 5b and 6b as well as the trehalose-type diblock methylcellulose analogue 4b (Yamagami et al 2018), as an authentic sample of a methylcellulose end-functionalized with a peptide, were synthesized according to the optimized reaction conditions for cellobiose derivatives 5a and 6a, as well as 4a. Figure 3 displays the 1 H-NMR spectra of compounds 4b, 5b, and 6b acquired in CDCl 3 .…”

“…In particular, thermoresponsive supramolecular hydrogels (Du et al 2015) with lower critical solution temperatures (LCSTs) (Yamagami et al 2018) enable the development of biomedical applications such as injectable drug-delivery technology (Baumann et al 2009). While poly(N-isopropylacrylamide) (Fundueanu et al 2009) is a well known thermoresponsive polymer derived from fossil resources, methylcellulose (MC) is a thermoresponsive material from renewable resources.…”

“…Consequently, we developed a synthetic method for the end-functionalization of methylcellulose to produce methylcellulosyl azide and propargyl methylcelluloside (Kamitakahara et al 2016). Moreover, not only did nonionic segments, such as cellobiosyl units (as hydrophilic blocks) induce thermoreversible hydrogelation, but ionic segments did as well (Yamagami et al 2018), although it was crucial that the concentrations of the diblock methylcellulose analogues in aqueous media remain at 4 wt%.…”