Monomer

Monomers typically used in ATRP are molecules with substituents that can stabilize the propagating radicals; for example, styrenes, (meth)acrylates, (meth)acrylamides, and acrylonitrile.^[7] ATRP is successful at leading to polymers of high number average molecular weight and low dispersity 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, catalyst, ligand, and solvent) are optimized in order for the concentration of the dormant species to be greater than that of the propagating radical while being low enough as to prevent slowing down or halting the reaction.^[8][9]

Initiator

The number of growing polymer chains is determined by the initiator. To ensure a low polydispersity and a controlled polymerization, the rate of initiation must be as fast or preferably faster than the rate of propagation ^[10] Ideally, all chains will be initiated in a very short period of time and will be propagated at the same rate. Initiators are typically chosen to be alkyl halides whose frameworks are similar to that of the propagating radical.^[8] Alkyl halides such as alkyl bromides are more reactive than alkyl chlorides. Both offer good molecular weight control.^[8][9] The shape or structure of the initiator influences polymer architecture. For example, initiators with multiple alkyl halide groups on a single core can lead to a star-like polymer shape.^[11] Furthermore, α-functionalized ATRP initiators can be used to synthesize hetero-telechelic polymers with a variety of chain-end groups^[12]

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. An equilibrium constant that is too small may inhibit or slow the polymerization while an equilibrium constant that is too large leads to a wide distribution of chain lengths.^[9]

There are several requirements for the metal catalyst:

1. There needs to be two accessible oxidation states that are differentiated by one electron
2. The metal center needs to have reasonable affinity for halogens
3. The coordination sphere of the metal needs to be expandable when it is oxidized as 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

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

Ligand

One of the most important aspects in an ATRP reaction is the choice of ligand which is used in combination with the traditionally copper halide catalyst to form the catalyst complex. The main function of the ligand is to solubilize the copper halide in whichever solvent is chosen and to adjust the redox potential of the copper.^[13] This changes the activity and dynamics of the halogen exchange reaction and subsequent activation and deactivation of the polymer chains during polymerization, therefore greatly affecting the kinetics of the reaction and the degree of control over the polymerization. Different ligands should be chosen based on the activity of the monomer and the choice of metal for the catalyst. As copper halides are primarily used as the catalyst, amine based ligands are most commonly chosen. Ligands with higher activities are being investigated as ways to potentially decrease the concentration of catalyst in the reaction since a more active catalyst complex would lead to a higher concentration of deactivator in the reaction. However, a too active catalyst can lead to a loss of control and increase the polydispersity of the resulting polymer.

Solvents

Toluene, 1,4-dioxane, xylene, anisole, DMF, DMSO, water, methanol, acetonitrile, or even the monomer itself (described as a bulk polymerization) are commonly used.

ATRP equilibrium constant

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

${\displaystyle [{\ce {R-P}}_{n}^{\bullet }]=K_{{\ce {ATRP}}}\cdot [{\ce {R-P}}_{n}{\ce {-X}}]\cdot {\frac {{\ce {[Cu^{I}X/L]}}}{{\ce {[Cu^{II}X2/L]}}}}}$

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:

${\displaystyle K_{\mathrm {ATRP} }^{22}={\dfrac {K_{\mathrm {ATRP} }^{12}\times K_{\mathrm {ATRP} }^{21}}{K_{\mathrm {ATRP} }^{11}}}}$

The K_ATRP values for different alkyl halides and different Cu catalysts can be found in literature.^[14]

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.^[15] 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.^[16]

Activation and deactivation rate coefficients

Deactivation rate coefficient, k_d, values must be sufficiently large to obtain low dispersity. The direct measurement of k_d is difficult though not impossible. In most cases, k_d may be calculated from known K_ATRP and k_a.^[14][17][18] Cu complexes providing very low k_d values are not recommended for use in ATRP reactions.

Retention of chain end functionality

${\displaystyle \sum [{\color {Red}{\ce {X}}}]={\ce {Constant}}}$

${\displaystyle \underbrace {{[{\color {Blue}{\ce {R}}}{-}{\color {Red}{\ce {X}}}]_{0}}-{[{\color {Blue}{\ce {R}}}{-}{\color {Red}{\ce {X}}}]}_{t}-{[{\color {Blue}{\ce {R}}}{-}{\ce {P}}_{\mathit {n}}{-}{\color {Red}{\ce {X}}}]}_{t}} _{\begin{matrix}{\text{Loss of chain}}\\{\text{end functionality}}\end{matrix}}=\underbrace {({[{\color {Green}{\ce {Cu^{I}}}}{\color {Red}{\ce {X}}}/{\ce {L}}]}_{t}+2{[{\color {Green}{\ce {Cu^{II}}}}{\color {Red}{\ce {X2}}}/{\ce {L}}]}_{t})-({{[{\color {Green}{\ce {Cu^{I}}}}{\color {Red}{\ce {X}}}/{\ce {L}}]_{0}}+2[{\color {Green}{\ce {Cu^{II}}}}{\color {Red}{\ce {X2}}}/{\ce {L}}]_{0}})} _{{\text{Change in }}{\ce {[Cu^{I}X/L]}}{\text{ and }}{\ce {[Cu^{II}X2/L]}}}+\underbrace {{[{\color {Orange}{\ce {RA}}}{-}{\color {Red}{\ce {X}}}]}_{t}} _{\begin{matrix}{\text{X transfer in}}\\{\text{activator}}\\{\text{regeneration}}\end{matrix}}}$

Halogen Conservation in Atom Transfer Radical Polymerization

High level retention of chain end functionality is typically desired. However, the determination of the loss of chain end functionality based on ¹H NMR and mass spectroscopy methods cannot provide precise values. As a result, it is difficult to identify the contributions of different chain breaking reactions in ATRP. One simple rule in ATRP comprises the principle of halogen conservation.^[19] Halogen conservation means the total amount of halogen in the reaction systems must remain as a constant. From this 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.^[20]

Advantages

ATRP enables the polymerization of a wide variety of monomers with different chemical functionalities, proving to be more tolerant of these functionalities than ionic polymerizations. It provides increased control of molecular weight, molecular architecture and polymer composition while maintaining a low polydispersity (1.05-1.2). The halogen remaining at the end of the polymer chain after polymerization allows for facile post-polymerization chain-end modification into different reactive functional groups. The use of multi-functional initiators facilitates the synthesis of lower-arm star polymers and telechelic polymers. External visible light stimulation ATRP has a high responding speed and excellent functional group tolerance.^[21]

Disadvantages

The most significant drawback of ATRP is the high concentrations of catalyst required for the reaction. This catalyst standardly consists of a copper halide and an amine-based ligand. The removal of the copper from the polymer after polymerization is often tedious and expensive, limiting ATRP's use in the commercial sector.^[22] However, researchers are currently developing methods which would limit the necessity of the catalyst concentration to ppm. ATRP is also a traditionally air-sensitive reaction normally requiring freeze-pump thaw cycles. However, techniques such as Activator Generated by Electron Transfer (AGET) ATRP provide potential alternatives which are not air-sensitive.^[23] A final disadvantage is the difficulty of conducting ATRP in aqueous media.

Activator regeneration ATRP methods

In a normal ATRP, the concentration of radicals is determined by the K_ATRP value, concentration of dormant species, and the [Cu^I]/[Cu^II] ratio. In principle, the total amount of Cu catalyst should not influence polymerization kinetics. However, the loss of chain end functionality slowly but irreversibly converts Cu^I to Cu^II. Thus initial [Cu^I]/[I] ratios are typically 0.1 to 1. When very low concentrations of catalysts are used, usually at the 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.

Other ATRP methods