# Microsphere Polymers in Molecular Imprinting: Current and Future Perspectives
## 3 Preparation of Molecularly Imprinted Microspheres
### Controlled/Living' Radical Precipitation Polymerisation (CRPP)
#### 3.2.1 Atom Transfer Radical Precipitation Polymerisation (ATRP)  
Since 1995, the atom transfer radical polymerisation (ATRP) approach has drawn considerable interest because of its versatility in polymer synthesis with specific functionalities and a wide scope of monomer, initiator and catalyst utilisation. The name ATRP stands for the atom transfer process, which is the main element that mediates the uniform growth of polymer chains. The reaction is based on a rapid and dynamic equilibrium among the active species (radicals) and dormant species (alkyl halides) with transition metal complexes that act as reversible halogen atom transfer reagents (Figure 2a). This system carries a very minimal radical concentration. ATRPP processes have a rate constant of activation (\(k_{\text{act}}\)) and deactivation (\(k_{\text{deact}}\)). Polymer chains mainly grow by capturing intermediate radicals to monomers with the rate constant of propagation (\(k_{\text{p}}\)). Termination with the rate constant of termination (\(k_{\text{t}}\)) additionally occurs, commonly through radical coupling and disproportionation; however, in well-controlled ATRP, less than 5% of growing polymer chains undergo termination. Initiators determine the end groups of polymers obtained by ATRP. For example, when the initiator is an alkyl halide (or arenesulphonyl halide), one end group of the polymer will be halide and the other end will be an alkyl (or arenesulphonyl) group. This characteristic is highly advantageous for further polymer surface modification [1; 125]. Two types of ATRP can be observed based on the initiation system, namely normal and reverse ATRP. In normal ATRP, initiator radicals originate from the reaction between alkyl halide and transition metal complexes in a lower oxidation state (e.g., Cu(I)/Ligand). As for reverse ATRP, initiator radicals originate from a conventional initiator (e.g., AlBN) at the onset of polymerisation, which are then deactivated by a transition-metal complex in its higher oxidation state (e.g., Cu(II)/ligand). The equilibrium for the active species (radicals) and dormant species (alkyl halide) of these types of system can be achieved rapidly at the beginning of the polymerisation process [125]. Atom transfer radical precipitation polymerisation (ATRP) is the incorporation of the ATRP system with a precipitation polymerisation procedure, which is simply a substitute for the conventional initiator (e.g., AIBN) with an ATRP initiator, such as the initiator in normal or reverse ATRPP (Figure 2b). Similarly to conventional precipitation polymerisation, the processes of nucleation and particle growth also occur in ATRPP. The difference between ATRPP and traditional radical precipitation polymerisation (TRPP) is, in ATRPP, all the ATRP initiators should be immediately converted into macroinitiators as soon as the process begins, which implies that the total yield of the newly formed polymer chains throughout the particle growth stage ought to be unimportant. Conversely, in TRPP, new oligomers are continuously produced during the process. In this manner, the mechanism of particle growth in ATRPP ought to be different from TRPP, as the polymer in ATRPP grows by catching monomers directly from the solution via the process of surface-initiated controlled polymerisation. This shows that the controlled attributes of ATRPP have major roles in uniform particle growth and size [126]. Furthermore, the presence of a surface-immobilised halogen group in the obtained MIMs facilitates  
Figure 2: The mechanism of atom transfer radical polymerisation (ATRP) (**a**) and ATRPP (**b**).