Synthesis of Monodisperse Cylindrical Nanoparticles via Crystallization-driven Self-assembly of Biodegradable Block Copolymers

Summary

Crystallization-driven self-assembly (CDSA) displays the unique ability to fabricate cylindrical nanostructures of narrow length distributions. The organocatalyzed ring-opening polymerization of ε-caprolactone and subsequent chain extensions of methyl methacrylate and N,N-dimethyl acrylamide are demonstrated. A living CDSA protocol that produces monodisperse cylinders up to 500 nm in length is outlined.

Abstract

The production of monodisperse cylindrical micelles is a significant challenge in polymer chemistry. Most cylindrical constructs formed from diblock copolymers are produced by one of three techniques: thin film rehydration, solvent switching or polymerization-induced self-assembly, and produce only flexible, polydisperse cylinders. Crystallization-driven self-assembly (CDSA) is a method which can produce cylinders with these properties, by stabilizing structures of a lower curvature due to the formation of a crystalline core. However, the living polymerization techniques by which most core-forming blocks are formed are not trivial processes and the CDSA process may yield unsatisfactory results if carried out incorrectly. Here, the synthesis of cylindrical nanoparticles from simple reagents is shown. The drying and purification of reagents prior to a ring-opening polymerization of ε-caprolactone catalyzed by diphenyl phosphate is described. This polymer is then chain extended by methyl methacrylate (MMA) followed by N,N-dimethyl acrylamide (DMA) using reversible addition−fragmentation chain-transfer (RAFT) polymerization, affording a triblock copolymer that can undergo CDSA in ethanol. The living CDSA process is outlined, the results of which yield cylindrical nanoparticles up to 500 nm in length and a length dispersity as low as 1.05. It is anticipated that these protocols will allow others to produce cylindrical nanostructures and elevate the field of CDSA in the future.

Introduction

One-dimensional (1D) nanostructures, such as cylinders, fibers and tubes, have garnered increasing attention in a variety of fields. Amongst these, their popularity in polymer science is owed to their rich variety of properties. For example, Geng et al. demonstrated that filomicelles exhibit a tenfold increase in residence time in the bloodstream of a rodent model compared to their spherical counterparts, and Won et al. revealed that polybutadiene-b-poly(ethylene oxide) fiber dispersions display an increase in storage modulus by two orders of magnitude upon crosslinking of the core during rheological measurements^1,

Protocol

1. Drying of toluene

NOTE: If you have access to dry solvent towers, collect the toluene and degas by five freeze-pump-thaw cycles.

1. Dry 3 Å molecular sieves in a 250 mL Schlenk flask at 250-300 °C under vacuum for 48 h and transfer into a glovebox.
2. Dry two ampoules in the oven at 150 °C overnight and transfer them into the glovebox.
3. Transfer the activated molecular sieves into the two ampoules and remove from the glovebox.
4. Dry a two-neck round-bottom flask (RBF) and add 100 mL of toluene, the volume of which equals to, at most, half of the ampoule volume. Add 1.0 g of CaH₂ ....

Results

PCL was analyzed by ¹H NMR spectroscopy and gel permeation chromatography (GPC). The ¹H NMR spectrum yielded a degree of polymerization (DP) of 50, by comparison of resonances at 3.36 ppm and 4.08 ppm, which correspond to the end group ethyl protons and the in-chain ester α-protons respectively (Figure 1b). This provided validation of the molecular weight values obtained by GPC where a single peak, with a dispersity value of 1.07, was ob.......

Discussion

The synthesis and living CDSA of the triblock copolymer PCL₅₀-PMMA₁₀-PDMA₂₀₀ has been outlined. Although stringent conditions are required, the ring-opening polymerization of ε-caprolactone gave polymers with excellent properties that enabled the successful chain extensions of MMA and DMA. These polymers were successful in their self-seeding, obtaining a pure phase of cylindrical micelles, which were sonicated into seed particles of L_N 98 nm. Through simple additi.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
2,2'-azobisisobutyrnitrile	Sigma Aldrich
250 mL ampoule
250 mL two neck RBF
Ampoule (25 mL)
B19 tap
B24 stopper
Basic Alumina	Fluka
Buchner Flask
Buchner Funnel
Caclium Hydride
Cannulae
caprolactone	Arcos Organics
Chain Transfer Agent	Made in House
Conical Flask (multiple sizes)
Dessicator
Diethyl Ether	Merck
Dioxane	Fisher
diphenylphosphate	Sigma Aldrich
Distillation Condenser
Ethanol	Fisher
Filter Paper (multiple sizes)
Gel Permeation Chrmoatography Instrument	Agilent Technologies Infinity 1260 II		Running DMF at 50 °C
Glovebox	Mbraun, Unilab
Hotplate	IKA, RCT basic
Mercury Thermometer
Methyl Methacrylate	Sigma Aldrich
Molecular seives	Fisher	MS/1030/53
N,N-dimethyl acrylamide	Sigma Aldrich
NMR spectrometer	Bruker 400 MHz
Phosphorus pentoxide	Sigma Aldrich
RBF (multiple sizes)
Schlenk Cap (B24)
Schlenk Flask (250 mL)
Schlenk Line
Sonication Probe	Bandelin Sonoplus
Suba Seal (multiple sizes)
TEM grids	EmResolutions, Formvar/carbon film 300 mesh copper
THF	Merck
three neck adaptor
Toluene	Fisher
Transmission Electron Microscope	Jeol 2100