RAFT Polymerization

Reversible Addition-Fragmentation Chain Transfer (RAFT) is a living free radical polymerization technique invented in 1998 by the Commonwealth Scientific and In- dustrial Research Organization (CSIRO) which is suited for the polymerization of a large family of functional monomers through its degenerative chain transfer process [167]. RAFT is frequently employed in areas such as drug delivery, tissue engineering, and membrane science among others [168–170]. Limitations of RAFT chemistry in- clude the lack of one or two universal chain transfer agents suited to all chemistries as well as difficulties encountered when extending this technique to efficiently fabricate block co-polymers when monomers differ in their reactivities [167].

RAFT chemistry establishes a kinetic control regime over the degree of polymer- ization which is unique from radical-radical terminations which are central to other radical polymerization methods. Specifically, this is accomplished through reversibly trapping the radical as chain growth commences. Dithioester chain transfer agents (also known as RAFT agents) capable of forming carbon centered radicals which can undergo β-scission or form leaving groups facillitate this chemistry. RAFT pro- vides the ability to fabricate novel architectures and useful end-group functionalities

through manipulation of the Z- and R-group chemistry of the chain transfer agent, which is not possible when using other well established polymerization techniques such as atom transfer radical polymerization (ATRP). An important factor in RAFT polymerization is the choice of a RAFT agent where the R group chemistry is am- menable to both β-scission and polymerization initiation, such that equilibrium is maintained between chain growth and the formation of dormant poly-RAFT agent where there is more dormant than active species [167].

In this work, the RAFT polymerization of tert-butyl acrylate (tBA) procedure reported by Liang et al [156] was adapted to fabricate ptBA with lengths ranging from 11 to 397 repeat units. This was accomplished mainly through controlling the amount of mononer used in the RAFT polymerization process, as will be discussed in detail later.

2.7.1 Synthesis of the RAFT Agent

Methyl-2-(butylthiocarbonothioylthio) propanoate, the RAFT agent employed in this work, was synthesized based on the procedure described in the enclosed reference [156]. The exact procedure was carried out as follows. A mixture of 10 ml of 1- butanethiol, 14.3 ml of triethylamine (TEA) and 100 ml of dichloromethane (DCM) was stirred under Ar before adding a mixture of 6.18 ml of carbon disulfide (CS2) and

50 ml of DCM over a 30 minute period using a syringe pump. After the addition the mixture was stirred for 1 hour prior to adding 11.46 ml of methyl-2-bromopropionate (MBP) in 50 ml of DCM over a 30 minute period using a syrringe pump. After stirring for 2 hours the excess solvent was evaporated and the remaining solid was dissolved in diethyl ether, causing the precipitation of a TEA-HBr salt which was subsequently filtered using filter paper and by pulling a light water-induced vacuum. The methyl- 2-(butylthiocarbonothioylthio) propanoate in ether was then washed thrice with both 50 ml of ice cold 10% HCl solution and 50 ml of DIW prior to drying overnight in a

vessel enclosed with anhydrous MgSO4. The ether was evaporated and the product

was purified by performing column chromatography with an in-house constructed 19:1 pentane/ethyl acetate column. Specifically, a packed slurry was made by adding quartz wool and 3 cm of SiO2to the bottom of a column followed by filling the column

half full with solvent. Subsequently, SiO2was added to the solvent to create the slurry

and the RAFT agent was dissolved in 5 ml of the 19:1 pentane/ethyl acetate mixture and added dropwise to the column. The second band was isolated.

2.7.2 RAFT Polymerization of tert-Butyl Acrylate

A typical polymerization was carried out as follows, using the procedure adapted from Liang et al [156]. 226.8 mg (0.90 mmol) of methyl-2-(butylthiocarbonothioylthio) propanoate, the RAFT agent, was added with 14.8 mg (0.90 mmol) of AIBN, the initiator, and 5.2 ml (36 mmol) tBA liquid monomer to a round bottom flask and purged for 30 minutes while stirring with Argon. A schematic of the appartus used, in lieu of the Schlenk tubes typically employed for air sensitive chemistry, is shown in Figure 2.20. Prior to use, 4-Methoxyphenol (MEHQ) inhibitor was removed from the tBA monomer by passing the tBA over a basic alumina column and discarding the first 5 ml. Additionally, the AIBN was purified by recrystallization in methanol. Polymerization was then initiated by heating the solution in an oil bath to 55◦_C

and holding for 1.5 hours, or until the stir bar stopped. The polymerization was subsequently quenched with liquid nitrogen before dissolution of the ptBA in the smallest possible volume of THF. The ptBA was then precipitated from the THF with 200-500 ml of ice cold 1/1 by volume methanol/water mixture, the exact amount depending on how much was needed for sufficient precipitation. The methanol/water mixture was then carefully decanted and the isolated polymer was dried under vacuum at room temperature overnight. The quoted procedure yielded polymers with 35.8 repeat units. Polymer lengths were tuned from 11 to 397 repeat units by adjusting

Figure 2.20: Experimental set-up for RAFT polymerization experiments the ratio of tBA mononer to RAFT agent.

2.7.3 Acid Hydrolysis of poly-tert-Butyl Acrylate

The ptBA prepared via RAFT polymerization was converted into polyacrylic acid (PAA) via acid hydrolysis prior to AuNP functionalization using methodology adapted from Wu et al [171]. Specifically, 2.5 g of ptBA was dissolved in 20 mL of 1,4-dioxane with 3 ml of 37% fuming HCl solution and heated while stirring under reflux at a temperature of 101◦C. The solution was refluxed until a visible layer of tert-butyl alcohol formed in the flask (typically 5+ hours), at which point the reflux condenser was removed and the tert-butyl alcohol was removed by evaporation while stirirng at 190◦C. The PAA was then precipitated from the 1,4-dioxane through the addition of ether which was then decanted from the precipitate. Finally, the PAA was dried under vacuum at room temperature overnight.

2.7.4 Preparation of Funtionalized PAA-AuNPs

The functionalization of prepared aqueous solutions of AuNPs with PAA was carried out using a procedure adapted from Liang et al [156]. In a typical functionalization, 15 mg of PAA in a 3 ml aqueous solution containing 0.1M NaHCO3was added to a 100

ml aqueous solution containing approximately 5 mg of AuNPs and stirred overnight. Following functionalization, the citrate and excess PAA were removed from solution through precipitation with ultracentrifugation at 100,000 g for 1 hour and washing with DIW (3 times).