Atom transfer radical polymerization

Overview of ATRP

ATRP usually employs a transition metal complex as the catalyst with an alkyl halide as the initiator (R-X). Various transition metal complexes, namely those of Cu, Fe, Ru, Ni, Os, etc., have been employed as catalysts for ATRP. In an ATRP process, the dormant species is activated by the transition metal complex to generate radicals via one electron transfer process. Simultaneously the transition metal is oxidized to higher oxidation state. This reversible process rapidly establishes an equilibrium that is predominately shifted to the side with very low radical concentrations. The number of polymer chains is determined by the number of initiators. Each growing chain has the same probability to propagate with monomers to form living/dormant polymer chains (R-P_n-X). As a result, polymers with similar molecular weights and narrow molecular weight distribution can be prepared.

ATRP reactions are very robust in that they are tolerant of many functional groups like allyl, amino, epoxy, hydroxy and vinyl groups present in either the monomer or the initiator. ATRP methods are also advantageous due to the ease of preparation, commercially available and inexpensive catalysts (copper complexes), pyridine based ligands and initiators (alkyl halides).

Components of Normal ATRP

There are four important variable components of Atom Transfer Radical Polymerizations. They are the monomer, initiator, catalyst and solvent. The following section breaks down the contributions of each component to the overall polymerization.

Monomer

Monomers that are typically used in ATRP are molecules with substituents that can stabilize the propagating radicals; for example, styrenes, (meth)acrylates, (meth)acrylamides, and acrylonitrile. ATRP are successful at leading to polymers of high number average molecular weight and a narrow polydispersity index when the concentration of the propagating radical balances the rate of radical termination. Yet, the propagating rate is unique to each individual monomer. Therefore, it is important that the other components of the polymerization (initiator, catalysts, ligands and solvents) are optimized in order for the concentration of the dormant species to be greater than the concentration of the propagating radical and yet not too great to slow down or halt the reaction.

Initiator

The number of growing polymer chains is determined by the initiator. Fast initiation ensures consistency of the number of propagating chains leading and to narrow molecular weight distributions. Organic halides that are similar in the organic framework as the propagating radical are often chosen as initiators. Most initiators for ATRP are alkyl halides. Alkyl halides such as alkyl bromides are more reactive than alkyl chlorides and both have good molecular weight control. The shape or structure of your initiator can determine the architecture of your polymer. For example, initiators with multiple alkyl halide groups on a single core can lead to a star-like polymer shape.

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Catalyst

The catalyst is the most important component of ATRP because it determines the equilibrium constant between the active and dormant species. This equilibrium determines the polymerization rate and an equilibrium constant too small may inhibit or slow the polymerization while an equilibrium constant too large leads to a high distribution of chain lengths.

There are several requirements for the metal catalyst:

1. there needs to be two accessible oxidation states that are separated by one electron
2. the metal center needs to have a reasonable affinity for halogens
3. the coordination sphere of the metal needs to be expandable when it is oxidized so to be able to accommodate the halogen
4. the transition metal catalyst should not lead to significant side reactions, such as irreversible coupling with the propagating radicals and catalytic radical termination, etc.

The most studied catalysts are those that include copper, which has shown the most versatility, with successful polymerizations for a wide selection of monomers.

Solvents

Toluene,1,4-dioxane, xylene, anisole, DMF, DMSO, water, methanol, acetonitrile, and other solvents are used.

Kinetics of Normal ATRP

ATRP Equilibrium Constant

The radical concentration in normal ATRP can be calculated via the following equation:

It is important to know the K_ATRP value to adjust the radical concentration. The K_ATRP value depends on the homo-cleavage energy of the alkyl halide and the redox potential of the Cu catalyst with different ligands. Given two alkyl halides (R¹-X and R²-X) and two ligands (L¹ and L²), there will be four combinations between different alkyl halides and ligands. Let K^ij_ATRP refer to the K_ATRP value for Rⁱ-X and L^j. If we know three of these four combinations, the fourth one can be calculated as K²²_ATRP=K¹²_ATRP × K²¹_ATRP / K¹¹_ATRP. The K_ATRP values for different alkyl halides and different Cu catalysts can be found in literature.

Solvents have significant effects on the K_ATRP values. The K_ATRP value increases dramatically with the polarity of the solvent for the same alkyl halide and the same Cu catalyst. The polymerization must take place in solvent/monomer mixture, which changes to solvent/monomer/polymer mixture gradually. The K_ATRP values could change 10000 times by switching the reaction medium from pure methyl acrylate to pure dimethyl sulfoxide.

Activation and Deactivation Rate Coefficients

Deactivation rate coefficient, k_d, values must be sufficiently large to obtain low M_w/M_n value. The direct measurement of k_d value is difficult though not impossible. In most cases the k_d values were calculated from known K_ATRP and k_a. Cu complexes giving very low k_d values are not recommended to be used in ATRP reactions.

Retention of Chain End Functionality

High level retention of chain end functionality is desired. However, the determination of the loss of chain end functionality based on ¹H NMR and MS methods cannot provide precise values. As a result, it is difficult to identify the contributions of different chain breaking reactions in ATRP. There is a simple rule in ATRP which is the principle of halogen conservation. Halogen conservation means the total amount of halogen in the reaction systems must remain as a constant. Based on the simple rule, the level of retention of chain end functionality can be precisely determined in many cases. The precise determination of the loss of chain end functionality enabled further investigation of the chain breaking reactions in ATRP.

Activator Regeneration ATRP Methods

In a normal ATRP, the concentration of radicals is determined by the K_ATRP value, concentration of dormant species and [Cu^I]/[Cu^II] ratio. In principle, the total amount of Cu catalyst should not influence the polymerization kinetics. However, the loss of chain end functionality slowly but irreversibly converts [Cu^I] to [Cu^II]. Thus the initial [Cu^I] is typically 0.1~1 equiv to the initiator. When very low concentrations of catalysts are used, usually at tens of ppm level, activator regeneration processes are generally required to compensate the loss of CEF and regenerate a sufficient amount of [Cu^I] to continue the polymerization. Several activator regeneration ATRP methods were developed, namely ICAR ATRP, ARGET ATRP, SARA ATRP, eATRP and Photoinduced ATRP. The activator regeneration process is introduced to compensate the loss of chain end functionality, thus the cumulative amount of activator regeneration should roughly equal the total amount of the loss of chain end functionality.

ICAR ATRP

Initiators for continuous activator regeneration (ICAR) is a technique that uses conventional radical initiators to continuously regenerate the activator, lowering its required concentration from thousands of ppm to <100 ppm; making it an industrially relevant technique.

ARGET ATRP

Activators regenerated by electron transfer (ARGET) employs non-radical forming reducing agents for regeneration of Cu^I. A good reducing agent (e.g. hydrazine, phenoles, sugars, ascorbic acid, etc...) should only react with Cu^II and not with radicals or other reagents in the reaction mixture.

SARA ATRP

A typical SARA ATRP employs Cu⁰ as both supplemental activator and reducing agent (SARA). Cu⁰ can activate alkyl halide directly but slowly. Cu⁰ can also reduce Cu^II to Cu^I. Both processes help to regenerate Cu^I activator. Other zero valent metals, such as Mg, Zn and Fe, have also been employed for Cu-based SARA ATRP.

eATRP

In eATRP the activator Cu^I is regenerated via electrochemical process. The development of eATRP enables precise control of the reduction process and external regulation of the polymerization. In an eATRP process, the redox reaction involves two electrodes. The Cu^II species is reduced to Cu^I at the cathode. The anode compartment is typically separated from the polymerization environment, by using a glass frit and a conductive gel. Alternatively, a sacrificial aluminum counter electrode can be used, which is directly immersed in the reaction mixture.

Photoinduced ATRP

The direct photo reduction of transition metal catalysts in ATRP and/or photo assistant activation of alkyl halide is particularly interesting because such a procedure will allow performing of ATRP with ppm level of catalysts without any other additives.

Reverse ATRP

In reverse ATRP, the catalyst is added in its higher oxidation state. Chains are activated by conventional radical initiators (e.g. AIBN) and deactivated by the transition metal. The source of transferrable halogen is the copper salt, so this must be present in concentrations comparable to the transition metal.

SR&NI ATRP

A mixture of radical initiator and active (lower oxidation state) catalyst allows for the creation of block copolymers (contaminated with homopolymer) which is impossible using standard reverse ATRP. This is called SR&NI (simultaneous reverse and normal initiation ATRP).

AGET ATRP

Activators generated by electron transfer uses a reducing agent unable to initiate new chains (instead of organic radicals) as regenerator for the low-valent metal. Examples are metallic Cu, tin(II), ascorbic acid, or triethylamine. It allows for lower concentrations of transition metals, and may also be possible in aqueous or dispersed media.

Hybrid and bimetallic systems

This technique uses a variety of different metals/oxidation states, possibly on solid supports, to act as activators/deactivators, possibly with reduced toxicity or sensitivity. Iron salts can, for example, efficiently activate alkyl halides but requires an efficient Cu(II) deactivator which can be present in much lower concentrations (3–5 mol%)

Metal-free ATRP

Trace metal catalyst remaining in the final product has limited the application of ATRP in biomedical and electronic fields. In 2014, Craig Hawker and coworkers developed a new catalysis system involving photoredox reaction of 10-phenothiazine. The metal-free ATRP has been demonstrated to be capable of controlled polymerization of methacrylates. This technique was later expanded to polymerization of acrylonitrile by Krzysztof Matyjaszewski et al.

Polymers Made by ATRP