Construction of nanostructures in aqueous solution from amphiphilic glucose‐derived polycarbonates

Abstract

This manuscript is dedicated to Professor Mitsuo Sawamoto's outstanding achievements in polymer chemistry and recognizes his recent retirement from 40 years of exceptional service to Kyoto University.ABSTRACT: Carbohydrates are the fundamental building blocks of many natural polymers, their wide bioavailability, high chemical functionality, and stereochemical diversity make them attractive starting materials for the development of new synthetic polymers. In this work, one such carbohydrate, D-glucopyranoside, was utilized to produce a hydrophobic five-membered cyclic carbonate monomer to afford sugar-based amphiphilic copolymers and block copolymers via organocatalyzed ring-opening polymerizations with 4-methylbenzyl alcohol and methoxy poly(ethylene glycol) as initiator and macroinitiator, respectively. To modulate the amphiphilicities of these polymers acidic benzylidene cleavage reactions were performed to deprotect the sugar repeat units and present hydrophilic hydroxyl side chain groups. Assembly of the polymers under aqueous conditions revealed interesting morphological differences, based on the polymer molar mass and repeat unit composition. The initial polymers, prior to the removal of the benzylidenes, underwent a morphological change from micelles to vesicles as the sugar block length was increased, causing a decrease in the hydrophilichydrophobic ratio. Deprotection of the sugar block increased the hydrophilicity and gave micellar morphologies. This tunable polymeric platform holds promise for the production of advanced materials for implementation in a diverse range of applications.Morphological control over the supramolecular assembly of amphiphilic polymers has been studied widely in the bulk and solution states. [21][22][23][24][25][26] A key advantage for amphiphilic polymers and block polymers is their ability to undergo assembly in water. The self-assembly of amphiphilic block copolymers into micelles or other nanostructures in aqueous solution allows Additional supporting information may be found in the online version of this article. † Shota Osumi and Simcha E. Felder contributed equally to this study.

Experiments and Simulations of Complex Sugar-Based Coil−Brush Block Polymer Nanoassemblies in Aqueous Solution

“…Instrumentation. 1 H NMR and 13 C NMR spectra were recorded on a Varian Inova 500 spectrometer (Varian, Inc., Palo Alto, CA, USA) interfaced to a UNIX computer using the VnmrJ software. Chemical shifts for 1 H NMR and 13 C NMR signals were referenced to the solvent resonance frequencies.…”

“…1 H NMR and 13 C NMR spectra were recorded on a Varian Inova 500 spectrometer (Varian, Inc., Palo Alto, CA, USA) interfaced to a UNIX computer using the VnmrJ software. Chemical shifts for 1 H NMR and 13 C NMR signals were referenced to the solvent resonance frequencies. Fourier transform infrared (FT-IR) spectra were recorded on an IR Prestige 21 system, equipped with a diamond attenuated total reflection (ATR) lens (Shimadzu Corp., Japan), and analyzed using IRsolution v. 1.40 software.…”

“…In a 25 mL Schlenk flask charged with a stir bar, the exo-5-norbornenecarboxylic acid (283 mg, 2.05 mmol, 1.0 equiv), N-hydroxysuccinimide (320 mg, 2.78 mmol, 1.4 equiv), and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDCI•HCl) (470 mg, 3.03 mmol, 1.5 equiv) were allowed to stir in 10 mL of anhydrous DCM for 20 h under nitrogen flow at room temperature. The reaction mixture was concentrated under reduced pressure, and N-hydroxysuccinimidyl ester was purified by flash chromatography (100% DCM as eluent) to afford 1 as a white powder (482 mg, 1.70 mmol, 83% yield): 1 H NMR (500 MHz, CDCl 3 ) δ ppm 6.19 (dd, J = 6, 3 Hz, 1H), 6.13 (dd, J = 6, 3 Hz, 1H), 3.25 (s, 1H), 2.99 (s, 1H), 2.81 (d, J = 4 Hz, 5H), 2.49 (dd, J = 9, 4 Hz, 1H), 2.03 (dt, J = 12, 4 Hz, 1H), 1.59−1.47 (m, 2H), 1.43 (d, J = 9 Hz, 1H); 13 General Procedure for Synthesis of Hydrophobic Macromonomers, exo-Norbornene-Terminated Poly(glucose carbonate)s (NB-PGCs). To a solution of the monomer GC (100 mg, 0.275 mmol) in anhydrous DCM (500 μL) was added exo-5norbornene-2-methanol (1.11 μL, 0.009 60 mmol).…”

“…First, norbornenylfunctionalized NHS ester 1 (NB-NHS) was synthesized in 83% yield by carbodiimide-mediated coupling of exonorbornene carboxylic acid and NHS in dichloromethane at room temperature followed by purification by flash chromatography. The structure was confirmed by electrospray ionization mass spectrometry (ESI-MS) and Fourier-transform infrared and 1 H and 13 C NMR spectroscopies (Figure S1). Second, a series of hydrophobic norbornene-terminated macromonomers 2 (Table S1) with different chain lengths was synthesized by organocatalyzed ROP of the bicyclic Dglucose-based carbonate monomer methyl-2,3-O-ethyloxycarbonyl-4,6-O-carbonyl-α-D-glucopyranoside at −78 °C using exo-5-norbornene-2-methanol as the initiator, according to a previously established procedure.…”

“…Obtaining more complex nanostructures has long fascinated researchers at the interface of biology, chemistry, materials science, and medicine − and motivated the design of amphiphilic macromolecules with degradability, e . g ., polyesters, polypeptides, and polycarbonates, − as well as sophisticated architectures, e . g ., cyclic, bottlebrush, and branched structures. − Precisely constructed brush polymers are of increasing interest, especially multifunctional bottlebrushes that are capable of supramolecular assembly into biologically active nanomaterials, due to their physicochemical properties, such as their extended backbone conformation, hindered entanglement, and feasibility as nanoscopic molecular building blocks with tunable relative concentric and lengthwise dimensions. − Coil–brush block polymers, also known as linear- block -brush polymers, contain both a flexible linear structure and a bulky bottlebrush structure, resulting in a wide range of compositional variables over both blocks, individually, as well as their combined two-dimensional architectures.…”