RAFT (chemistry)
Encyclopedia
Reversible Addition-Fragmentation chain Transfer or RAFT polymerization is one kind of controlled radical polymerization. Discovered at the Commonwealth Scientific and Industrial Research Organisation
(CSIRO) in 1998, RAFT polymerization is a relatively new method for the synthesis of living
radical
polymers that may be more versatile than other living polymerization techniques, such as atom transfer radical polymerization
(ATRP) or nitroxide-mediated polymerization (NMP). RAFT polymerization uses thiocarbonylthio compounds, such as dithioesters, thiocarbamates, and xanthate
s, to mediate the polymerization via a reversible chain-transfer process. As with other controlled radical polymerization techniques, RAFT generally yields polymers with a low polydispersity index and a predetermined molecular weight. RAFT polymerization can be used to design polymers of complex architectures, such as linear block copolymers, comb-like, star, brush polymers and dendrimer
s.
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 reported 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, including aqueous solutions. RAFT polymerization has also been effectively carried out over a wide temperature range.
RAFT polymerization can be performed by simply 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.
Because of the low concentration of the RAFT agent in the system, the concentration of the initiator is usually lower than in conventional radical polymerization. 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.
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 an important role - it must be a good homolytic leaving group which is able to initiate new polymer chains.
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. It is a 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.
RAFT polymerization may be performed on many monomers to yield polymers of varying molecular weights and low PDIs. As seen in Figure 4, poly(methyl methacrylate) and polyacrylic acid
have been synthesized using AIBN as the initiator and various dithioester compounds.
(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.
Multiblock copolymers have also been reported by using difunctional R groups or symmetrical trithiocarbonates with difunctional Z groups.
s, 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.
Commonwealth Scientific and Industrial Research Organisation
The Commonwealth Scientific and Industrial Research Organisation is the national government body for scientific research in Australia...
(CSIRO) in 1998, RAFT polymerization is a relatively new method for the synthesis of living
Living polymerization
In polymer chemistry, living polymerization is a form of addition polymerization where the ability of a growing polymer chain to terminate has been removed. This can be accomplished in a variety of ways. Chain termination and chain transfer reactions are absent and the rate of chain initiation is...
radical
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
polymers that may be more versatile than other living polymerization techniques, such as atom transfer radical polymerization
ATRP (chemistry)
Atom transfer radical polymerization is an example of a living polymerization or a controlled/living radical polymerization . Like its counter part, ATRA or atom transfer radical addition, it is a means of forming carbon-carbon bond through transition metal catalyst...
(ATRP) or nitroxide-mediated polymerization (NMP). RAFT polymerization uses thiocarbonylthio compounds, such as dithioesters, thiocarbamates, and xanthate
Xanthate
Xanthate usually refers to a salt with the formula ROCS2-M+ . The name xanthates is derived from Greek ξανθός , meaning “yellowish, golden”, and indeed most xanthate salts are yellow...
s, to mediate the polymerization via a reversible chain-transfer process. As with other controlled radical polymerization techniques, RAFT generally yields polymers with a low polydispersity index and a predetermined molecular weight. RAFT polymerization can be used to design polymers of complex architectures, such as linear block copolymers, comb-like, star, brush polymers and dendrimer
Dendrimer
Dendrimers are repetitively branched molecules. The name comes from the Greek word "δένδρον" , which translates to "tree". Synonymous terms for dendrimer include arborols and cascade molecules. However, dendrimer is currently the internationally accepted term. A dendrimer is typically symmetric...
s.
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-functionalized 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 reported 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, including aqueous solutions. RAFT polymerization has also been effectively carried out over a wide temperature range.
Important Components of RAFT
Typically, a RAFT polymerization system consists of:- initiator
- monomerMonomerA monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
- chain transfer agent
- solvent
- temperature
RAFT polymerization can be performed by simply 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.
Because of the low concentration of the RAFT agent in the system, the concentration of the initiator is usually lower than in conventional radical polymerization. Radical initiators such as Azobisisobutyronitrile(AIBN) and 4,4'-Azobis(4-cyanovaleric acid) (ACVA) which is also called 4,4'-Azobis(4-cyanopentanoic acid)
4,4'-Azobis(4-cyanopentanoic acid)
4,4'-Azobis is a free radical initiator used in polymer synthesis it is used as one of the initiators in Reversible addition−fragmentation chain transfer polymerization when heated to decomposition it releases vapours of NOx....
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 an important role - it must be a good homolytic leaving group which is able to initiate new polymer chains.
RAFT Mechanism
RAFT is a type of living polymerizationLiving polymerization
In polymer chemistry, living polymerization is a form of addition polymerization where the ability of a growing polymer chain to terminate has been removed. This can be accomplished in a variety of ways. Chain termination and chain transfer reactions are absent and the rate of chain initiation is...
involving a conventional radical polymerization
Radical polymerization
Free radical polymerization is a method of polymerization by which a polymer forms by the successive addition of free radical building blocks. Free radicals can be formed via a number of different mechanisms usually involving separate initiator molecules...
in the presence of a reversible chain transfer reagent. Like other living polymerizations, there is no termination step in the RAFT process. It is a 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
Radical initiator
In chemistry, radical initiators are substances that can produce radical species under mild conditions and promote radical reactions . These substances generally possess weak bonds—bonds that have small bond dissociation energies. Radical initiators are utilized in industrial processes such...
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
Disproportionation
Disproportionation, also known as dismutation is used to describe a specific type of redox reaction in which a species is simultaneously reduced and oxidized so as to form two different products....
, increasing the polymer length.
RAFT polymerization may be performed on many monomers to yield polymers of varying molecular weights and low PDIs. As seen in Figure 4, poly(methyl methacrylate) and polyacrylic acid
Polyacrylic acid
Poly or PAA or Carbomer is a type of anionic polymer. The monomer of poly is acrylic acid. In a water solution at neutral pH, many of the side chains of PAA will lose their protons and acquire a negative charge. This makes PAA a polyelectrolyte.Dry PAA is a white solid...
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 polydispersitiesPolydispersity index
In physical and organic chemistry, the polydispersity index , is a measure of the distribution of molecular mass in a given polymer sample. The PDI calculated is the weight average molecular weight divided by the number average molecular weight. It indicates the distribution of individual...
(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
Branching (chemistry)
In polymer chemistry, branching occurs by the replacement of a substituent, e.g., a hydrogen atom, on a monomer subunit, by another covalently bonded chain of that polymer; or, in the case of a graft copolymer, by a chain of another type...
such as block, gradient
Gradient copolymers
Copolymers are polymers that are synthesized with more than one kind of repeat unit . It exhibits a gradual change in monomer composition from predominantly one species to predominantly the other, unlike with block copolymers, which have an abrupt change in composition, and random copolymers,...
, 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 living radical polymerization techniques because the core of the copolymer can be introduced by functionalization of either the R group or the Z group. 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.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 monomerMonomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
s, 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.
See also
- Radical (chemistry)Radical (chemistry)Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
- Copolymer
- Living polymerizationLiving polymerizationIn polymer chemistry, living polymerization is a form of addition polymerization where the ability of a growing polymer chain to terminate has been removed. This can be accomplished in a variety of ways. Chain termination and chain transfer reactions are absent and the rate of chain initiation is...
- ATRP (chemistry)ATRP (chemistry)Atom transfer radical polymerization is an example of a living polymerization or a controlled/living radical polymerization . Like its counter part, ATRA or atom transfer radical addition, it is a means of forming carbon-carbon bond through transition metal catalyst...