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RAFT or Reversible Addition-Fragmentation chain Transfer polymerization is one kind of controlled radical polymerizations. Reversible addition–fragmentation chain transfer polymerization was discovered by the CSIRO in 1998. This is a relatively new method for the synthesis of living radical polymers that may be more versatile than atom transfer radical polymerization (ATRP) or Nitroxide-Mediated Polymerization|nitroxide-mediated polymerization (NMP). RAFT polymerization uses thiocarbonylthio compounds, such as dithioesters, dithiocarbamates, trithiocarbonates, and xanthates in order to mediate the polymerization via a reversible chain-transfer process. This allows access to polymers with low polydispersity and high functionality. RAFT is also known for its compatibility with a great variety of monomers, solvents and reaction conditions.

With respect to its exceptional effectiveness and the wide range of applicable monomers as well as solvents, RAFT polymerization has developed into an extremely versatile polymerization technique. Indeed, the molecular weight of the polymer can be easily predetermined and the molecular weight distribution can be controlled fairly well. Moreover, RAFT polymerization is used to design polymers of complex architectures such as linear block, comb-like, star, brush polymers and dendrimers.

History
Addition-fragmentation chain transfer process was first reported in the early 1970s. 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-functional polymers.

Scientists began to realize the potential of RAFT in controlled radical polymerization in the 1980s. 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.

RAFT polymerization today is mainly carried out by thiocarbonylthio chain transfer agents. It was first report by Thang et al in 1998. 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. RAFT polymerization has also been effectively carried our over a wide temperature range.

Important Components of RAFT
Typically, a RAFT polymerization system consists of:
 * initiator
 * monomer
 * chain transfer agent
 * solvent
 * temperature

RAFT polymerization can be performed by simply adding a chosen quantity of an appropriate RAFT agent to a conventional free radical polymerization. Usually the same monomers, initiators, solvents and temperatures can be used.

Because of the low concentration of RAFT agent in the system, the concentration of initiator is usually lower than that in conventional radical polymerization. Radical initiators such as Azobisisobutyronitrile(AIBN) and 4,4'-Azobis(4-cyanovaleric acid)(ACVA) are widely used as the initiator in RAFT.

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 (also called chain-transfer agents) must be thiocarbonylthio compounds where the Z and R groups perform different functions. The Z group primarily controls the ease with which radical species add to the C=S bond. The R group plays two important roles--it must be a good homolytic leaving group and the expelled radical R· must be able to add to monomer.

RAFT Mechanism
RAFT is a type of living polymerization involving a conventional radical polymerization in the presence of a reversible chain transfer reagent. Like other living polymerizations, there is no termination step in the RAFT process, leading to very large molecular weight polymers. It is an very versatile method to form low polydispersity polymer from monomers capable of radical polymerization. The reaction is usually done with a dithioester. The dithio compound must have a good homolytic leaving group, R, whose radical must be capable of initiating a polymerization reaction. There are four steps in raft polymerization: initiation, addition-fragmentation, reinitiation and equilibration.

Initiation: The reaction is started by radical initators  such as  AIBN. In this step, the initiator (I) reacts with a monomer unit to create a radical species which starts an active polymerizing chain.

Addition-Fragmentation: The active chain (Pn) reacts with the dithioester, which kicks out the homolytic leaving group (R). This is a reversible step, with an intermediate species capable of losing either the leaving group (R) or the active species (Pn).

Reinitiation: The leaving group radical then reacts with another monomer species, starting another active polymer chain. This active chain (Pm) is then able to go through the addition-fragmentation or equilibration steps.

Equilibration: This is the fundamental step in the RAFT process which traps the majority of the active propagating species into the dormant thiocarbonyl compound. This limits the possibility of chain termination through. Active polymer chains (Pm> and Pn) are in an equilibrium between the active and dormant stages. While one polymer chain is in the dormant stage (bound to the thiocarbonyl compound), the other is active in polymerization.

By controlling the concentration of initiator and capping agent (dithioester), it is possible to produce controlled molecular weight with low polydispersities. In RAFT polymerization, the concentration on the active species is kept low relative to the dormant species by controlling the amount of initiator and capping agent. This in turn will limit termination steps such as radical combination and disproportionation, increasing the polymer length.

Many High molecular weight polymers with low PDIs have been synthesized using RAFT polymerization. As seen in Figure 4, poly(methyl methacrylate) and polyacrylic acid have been synthesized using AIBN as the initiator and various dithioester compounds.



Applications
RAFT polymerization has successfully synthesized a wide range of polymers with controlled molecular weight and low polydispersities. 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.

Block Copolymers
Because RAFT is a form of living radical polymerization, it is ideal for 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).

Multiblock copolymers have also been reported by using difunctional R groups or symmetrical trithiocarbonates with difunctional Z groups.

Star Copolymers
Using a multifuntional CTA can result in the formation of a star copolymer. RAFT differs from other forms of LRPs because the core of the copolymer can be introduced by functionalization of either the R group or the Z group. While utilizing the R groupresults 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.

Controlled Grafting onto Polymeric Surfaces
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.

Drug Delivery
In the design of polymer-protein or polymer-drug conjugates, a specific polymerization technique is required. This technique must need inexpensive reagents and not require expensive instrumentation, the reaction must be performable in a standard laboratory, and no complicated purification should be necessary. For such a demanding scheme, RAFT appears to dominate over other forms of polymerization. With the ability to form complex architectures with a large variety of monomers, new types of polymers are able to be constructed with unique properties, such as temperature and pH sensitivity. These properties open up the possibility of using polymers for control of enzyme activity or molecular recognition processes. Additionally, polymers with these properties could be manufactured to form micelles allowing it to contain a drug for site-specific delivery.