Reversible Addition-Fragmentation chain Transfer or RAFT polymerization is one of several kinds of controlled radical polymerization. It makes use of a chain transfer agent in the form of a dithioester (or similar compounds, from here on referred to as RAFT agents, see Figure 1) to afford control over the generated molecular weight and polyispersity in the formed polymers. Discovered at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in 1998, RAFT polymerization is one of several living or Controlled radical polymerization techniques, othes being atom transfer radical polymerization (ATRP) and nitroxide-mediated polymerization (NMP). RAFT polymerization uses thiocarbonylthio compounds,[1] such as dithioesters, thiocarbamates, and xanthates, to mediate the polymerization via a reversible chain-transfer process. As with other controlled radical polymerization techniques, RAFT polymerizations can be performed with conditions to favor low polydispersity indices and a pre-chosen. RAFT polymerization can be used to design polymers of complex architectures, such as linear block copolymers, comb-like, star, brush polymers and dendrimers.
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Addition-fragmentation chain transfer process was first reported in the early 1970s.[2] However, the technique was irreversible so the transfer reagents could not be selected to control radical polymerization at this time. For the first few years RAFT was used to help synthesize end-functionalized polymers.
Scientists began to realize the potential of RAFT in controlled radical polymerization in the 1980s.[3] Macromonomers were known as reversible chain transfer agents during this time, but had limited applications on controlled radical polymerization.
In 1995, a key step in the “degenerate” reversible chain transfer step for chain equilibration was brought to attention. The essential feature is that the product of chain transfer is also a chain transfer agent with similar activity to the precursor transfer agent.[4]
RAFT polymerization today is mainly carried out by thiocarbonylthio chain transfer agents. It was first reported by Thang et al. in 1998.[5] RAFT is one of the most versatile methods of controlled radical polymerization because it is tolerant of a very wide range of functionality in the monomer and solvent, including aqueous solutions.[6] RAFT polymerization has also been effectively carried out over a wide temperature range.
Typically, a RAFT polymerization system consists of:
A temperature is chosen such that chain growth occurs at an appropriate rate, the chemical initiator (radical source) delivers radicals at an appropriate rate and the central RAFT equilibrium (see later) favors the active rather than domant state to an acceptable extent.
RAFT polymerization can be performed by adding a chosen quantity of an appropriate RAFT agent (thiocarbonylthio compounds) to a conventional free radical polymerization. Usually the same monomers, initiators, solvents and temperatures can be used.
Radical initiators such as Azobisisobutyronitrile(AIBN) and 4,4'-Azobis(4-cyanovaleric acid) (ACVA) which is also called 4,4'-Azobis(4-cyanopentanoic acid) are widely used as the initiator in RAFT.
Figure 3 provides a visual description of RAFT polymerizations of poly(methyl methacrylate) and polyacrylic acid using AIBN as the initiator and two RAFT agents.
RAFT polymerization is known for its compatibility with a wide range of monomers compared to other controlled radical polymerizations. These monomers include (meth)acrylates, (meth)acrylamides, acrylonitrile, styrene and derivatives, butadiene, vinyl acetate and N-vinylpyrrolidone.
RAFT agents are thiocarbonylthio compounds (or dithioesters) with the Z and R chosen according to a number of considerations. The Z group primarily affects the stability of the S=C bond and the stabiity of the adduct radical. These in turn affect the position of and rates of the elementary reactions in the pre- and main- equilibrium. The R group must be able to stabilize a radical such that the right hand side of the pre-equilibrium is favoured, but unstable enough such that it can reinitiate growth of a new polymer chain. As such, a RAFT agent must be designed with consideration of the monomer and temperature, since both these parameters also strongly influence the kinetics and thermodynamics of the RAFT equilibria.
RAFT is a type of living polymerization involving a conventional radical polymerization which is mediated by a RAFT agent.[7] Monomers must be capable of radical polymerization.[8] There are a number of steps in a RAFT polymerization: initiation, pre-equilbrium, re-initiation, main equilibrium, propagation and termination.
The mechanism is now explained with the help of Figure 4.
Initiation: The reaction is started by a free-radical source which may be a chemical radical initators such as AIBN. In the example in Figure 3, the initiator decomposes to form two fragments (I•) which react with a single monomer molecule to yield a polymeric radical of length 1, denoted P1•.
Propagation: Polymeric chains of length n in their active (radical) form, Pn•, add to monomer to form longer propagating radicals, Pn+1•.
RAFT pre-equilibrium: A polymeric radical with n monomer units (Pn) reacts with the dithioester to form a RAFT adduct radical. This may undergo a fragmentation reaction in either direction to yield either the starting species or a radical (R•) and a polymeric RAFT agent (RAFT-Pn). This is a reversible step in which the intermediate RAFT adduct radical is capable of losing either the R group (R•) or the polymeric species (Pn•).
Re-initiation: The leaving group radical (R•) then reacts with another monomer species, starting another active polymer chain.
Main RAFT equilibrium: This is the most important part in the RAFT process[7], in which, by a process of rapid interchange, the present radicals (an hence opportunities for polymer chain growth) are shared among all species that have not yet undergone termination (Pn• and RAFT-Pn).
Termination: Chains in their active form react via a process known as bi-radical termination to form chains that cannot react further, know as dead polymer. Ideally, the RAFT adduct radical is sufficiently hindered such that it does not undergo termination reactions.
In terms of mechanism, an ideal RAFT polymerisation has several features. The pre-equilibrium and re-initiation steps are completed very early in the polymerisation meaning that the major product of the reaction (the RAFT polymer chains, RAFT-Pn), all start growing at approximately the same time. The forwards and reverse reactions of the main RAFT equilibrium are fast, favoring equal growth opportunities amongst the chains. The total number of radicals delivered to the system by the initiator during the course of the polymerisation is low compared to the number of RAFT agent molecules, meaning that the R group bearing species from the Re-initiation step form the majority of the chains in the system, rather than initiator fragment bearing chains formed in the Initiation step. This is important because initiator decomposes continuously during the poolymerisation, not just at the start, and polymer chains arising from initiator decmposition cannot, therefore, have a narrow length distribution. These mechanistic features lead to an average chain length that increases linearly with the conversion of monomer into polymer.
A RAFT polymerization does not achieve controlled evolution of molecular weight and low polydispersity by reducing bi-radical termination events (although in some systems, these events may indeed be reduced somewhat), but rather, by ensuring that most polymer chains start growing at approximately the same time and grow together throughout the polymerization.
RAFT polymerization has successfully synthesized a wide range of polymers with controlled molecular weight and low polydispersities (between 1.05 and 1.4 for many monomers).
Some monomers capable of polymerizing by RAFT include styrenes, acrylates, acrylamides, and many vinyl monomers. Additionally, the RAFT process allows the synthesis of polymers with specific macromolecular architectures such as block, gradient, statistical, comb/brush, star, hyperbranched, and network copolymers. These properties make RAFT useful in many types of polymer synthesis.[9]
As with other living radical polymerization techniques, RAFT may be used for the synthesis of block copolymers. For example, in the copolymerization of two monomers (A and B) allowing A to polymerize via RAFT will exhaust the monomer in solution without termination. After monomer A is fully reacted, the addition of monomer B will result in a block copolymer. One requirement for maintaining a narrow polydispersity in this type of copolymer is to have a chain transfer agent with a high transfer constant to the subsequent monomer (monomer B in the example).[9]
Multiblock copolymers have also been reported by using difunctional R groups or symmetrical trithiocarbonates with difunctional Z groups.
Using a compound with multiple dithio moieties (often termed a star or multifunctional RAFT agent) can result in the formation of a star polymer. RAFT differs from other forms of living radical polymerization techniques in that either the R- or Z-group may form the core of the star. While utilizing the R group results in similar structures found using ATRP or NMP, the use of the Z group makes RAFT unique. When the Z group is used, the reactive polymeric arms are detached from the core while they grow and react back into the core for the chain-transfer reaction.[9]
Producing grafted polymers onto a polymer bead via non-controlled radical polymerization results in a broad molecular weight distribution and high polydispersity. Even when using other controlled radical polymerization techniques (such as ATRP) polymeric microspheres would often require derivitization.By employing RAFT polymerization, grafting from these microspheres becomes a one-step process. Furthermore the grafted polymer would have a RAFT end group, leading to the possibility of reinitiating the chains to form block copolymer shells.[10]
Due to its flexibility with respect to the choice of monomers and reaction conditions, the RAFT process competes favorably with other forms of living polymerization for the generation of bio-materials. New types of polymers are able to be constructed with unique properties, such as temperature and pH sensitivity.
Specific materials and their applications include polymer-protein and polymer-drug conjugates, mediation of enzyme activity, molecular recognition processes and polymeric micelles which can deliver a drug to a specific site in the body.[11][12]
Polymerizations can be performed in large range of solvents (including water), within a wide temperature range, is suitable for use with many dfferent monomers and does not require highly rigorous removal of oxygen and other impurities.
A particular RAFT agent is only suitiable for a limited set of monomers and the synthesis of a RAFT agent typically requires a multistep synthetic procedure. RAFT agents can be unstable over long time periods, are highly colored and can have a pungent odor due to gradual decomposition of the dithioester moiety to yield small sulfur compounds. The presence of sulfur and color in the resulting polymer may also be undesirable for some applications; however, this can, to an extent, be eliminated with further chemical and physical purifiation steps.[13]