# Green Strategies for Molecularly Imprinted Polymer Development
## 1 Introduction  
Green chemistry or sustainable chemistry can be defined as the design of chemical products and processes through the utilization of a set of principles able to reduce or eliminate the use or generation of hazardous substances. There are 12 principles of green chemistry and 12 principles of green engineering that should be followed to meet sustainability. These principles can be applied over the whole life cycle of a product, from its design, manufacture, and use, to its final disposal [1; 2].  
Herein we give an overview of how these green principles are being applied to the field of molecular imprinting. Many advances in the synthetic approaches have been made in the last years, however, molecular imprinting methodology still uses high quantities of solvents and intensive process steps, and this has, in our opinion, contributed for a difficult process adaptation and application of molecularly imprinted polymers (MIPs) at industrial scale, and hampered their wide use as real alternatives as affinity materials. Examples reported in literature will be shown, where green technologies and alternative solvents are used in MIP synthesis, as well as, tools for MIP design that can significantly decrease time and laboratory costs in MIP optimization.  
In molecular imprinting, the formation of interaction complexes between the molecule of interest (template) and the functional monomers in the presence of a crosslinker and a porogen solvent, enable the production of specific sites within the polymeric material that are physically and chemically complementary to the template. After removing the template, the cavity is able to selectively bindthe molecule in the final MIP application. The recognition mechanism can be mediated by different interactions, such as weak non-covalent hydrogen bonding interactions, ion-pairing, hydrophobic, or dipolar interactions. In addition, MIPs can be prepared according to different approaches, i.e., non-covalent, covalent, and semi-covalent, which differ in the way the template interacts with the functional monomer and with the polymeric binding sites in the final application.  
Conventional MIP production techniques include polymerization in bulk, precipitation, emulsion, multi-step swelling, suspension, gelation, etc. The final particle sizes can vary from nano- to micron-sized particles, from irregular to completely spherical particles. MIPs can also be obtained in different final structures depending on the final application: membranes, fibers, core-shell particles, etc.  
The affinity properties of MIPs are well recognized. MIPs are robust and present binding affinity constants similar to natural molecules [3]. Nevertheless, they also have some disadvantages. When they are prepared in bulk, the polymer must be crushed and sieved in a very time-consuming process, where very irregular particles are obtained. Conventional techniques also use high quantities of organic solvents. Water could be a good alternative, however, it can typically form strong interactions with the template and/or the monomers, and this would destabilize the formation of the complex and interfere in the formation of the specific sites. The use of green alternative solvents can overcome many of the disadvantages of MIP traditional production methodologies.