Controlled radical polymerization of α-Lipoic acid: A general route to degradable vinyl copolymers

Here, we present the synthesis and characterization of statistical and block copolymers containing α-lipoic acid (LA) using reversible addition–fragmentation transfer (RAFT) polymerization. LA, a readily available nutritional supplement, undergoes efficient radical ring-opening copolymerization with vinyl monomers in a controlled manner with predictable molecular weights and low molar-mass dispersities. Because lipoic-acid diads present in the resulting copolymers include disulfide bonds, these copolymers efficiently and rapidly degrade when exposed to mild reducing agents such as tris(2-carboxyethyl)phosphine (Mn = 56 kg mol–1 → 3.6 kg mol–1). This scalable and versatile polymerization method affords a facile way to synthesize degradable polymers with controlled architectures, molecular weights, and molar-mass dispersities from α-lipoic acid, a commercially available and renewable monomer.

Methods
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 or chloroform containing 0.25% TEA at 35 °C for the mobile phase. Molar masses and molar mass dispersities (Đ) were determined against narrow PS standards (Agilent).

Dynamic Light Scattering (DLS)

The DLS experiment was performed with disposable 4 mL plastic cuvettes for the DLS instrument with 1 mL of aqueous solution. The light scattering signals were measured by using a Marvin Instrument Ltd. nanoZS Zetasizer.

Photoluminescence

Solution-state photoluminescent data were obtained using a Jobin-Yvon HORIBA FluoroMax-4 (xenon source, 1.0 nm excitation, and emission slit widths, 1 nm step size, λexcitation = 536 nm) equipped with a solution-state sample holder and quartz cuvette with a diameter of 1 cm. Photoluminescent data were analyzed using the FluorEssence (v3.5) software powered by Origin. Samples were prepared according to the following: A stock solution of polymer (~2.2 mg) was dissolved in 100 µL of THF. The micelles were prepared by rapidly mixing the THF solution with 3 mL of Milli-Q water. With Nile red, a 1 µg/mL solution was added to the polymer THF solution prior to micelle formation. 

Thermal characterization

Thermogravimetric analysis (TGA) was performed under air on a TA Instruments Q500 at a heating rate of 10 °C min−1 with a sample size of ca. 10 mg. Differential Scanning Calorimetry (DSC) was performed using 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.