Scalable synthesis of degradable copolymers containing α‑lipoic 2 acid via miniemulsion polymerization

A robust method is described to synthesize degradable copolymers under aqueous miniemulsion conditions using α-lipoic acid as a cheap and scalable building block. Simple formulations of α-lipoic acid (up to 10 mol%), n-butyl acrylate, surfactant, and costabilizer generate stable micelles in water with particle sizes <200 nm. The ready availability of these starting materials facilitated performing polymerization reactions at large scales (4 L), yielding 600 g of poly(n-butyl acrylate–stat–α-lipoic acid) latexes that degrade under reducing conditions (250 kg mol–1 → 8 kg mol–1). Substitution of α-lipoic acid with ethyl lipoate further improves the solubility of dithiolane in n-butyl acrylate, resulting in copolymers that degrade to even lower molecular weights after polymerization and reduction. In summary, this simple and scalable strategy provides access to large quantities of degradable copolymers and particles using cheap and commercially available starting materials.

Methods
Molecular Characterization

1H nuclear magnetic resonance spectroscopy

Solution state 1H nuclear magnetic resonance (NMR) spectra were recorded on a Varian VNMRS 600 MHz spectrometer. Chemical shifts (δ) are reported in ppm relative to residual protio solvent in CDCl3 (7.26 ppm).

Size-exclusion chromatography instrumentation

Size-exclusion chromatography (SEC) was performed on a Waters instrument using a differential refractive index detector and two Tosoh columns (TSKgel SuperHZM-N, 3 μm polymer, 150 × 4.6 mm) with THF at 35 °C for the mobile phase. Molar masses and molar mass dispersities (Đ) were determined against narrow PS standards (Agilent).

Thermal Characterization

Differential scanning calorimetry (DSC) was performed with a TA Instruments DSC Q2000 at a heating/cooling rate of 10 °C/min using 3–5 mg of sample in a sealed aluminum pan. Thermogravimetric analysis (TGA) was performed under nitrogen on a TA Instruments Q500 at a heating rate of 10 °C min−1 with a sample size of ca. 4 mg.

Dispersion Preparation and Characterization

Ultrasonication

Emulsions were prepared using a Fisher Scientific Ultrasonication Horn model FB-705. Sonications were performed using an ice bath with frequency 20 KHz, amplitude 20 m, pulsing on for 5 sec, then off for 10 sec for a total processing time of 5 minutes.

Dynamic Light Scattering

Dynamic light scattering (DLS) measurements of the emulsions were taken using a DynaPro NanoStar™ from Wyatt Technology run at 25 C. The laser used emitted at 662 nm with an intensity of 100 mW. Disposable 1 L cuvettes were used.