# Green Strategies for Molecularly Imprinted Polymer Development
## Green Strategies in MIP Development
### Supercritical Fluid Technology
It is an endocrine disruptor that is commonly used in the production of polycarbonate plastics and epoxy resins [27], and it is known that the exposition to BPA increases the risk of cancer [28] and chronic diseases, such as diabetes [29]. BPA-imprinted polymer synthesis in scCO\({}_{2}\) is reported in the literature by [PERSON] et al. in 2012 [18; 19]. MIPs were produced by FRP, using two different strategies: non-covalent and semi-covalent imprinting. In the first approach, MAA was used as functional monomer and EGDMA as crosslinker, while in the second approach, bisphenol dimethacrylate (BPADM) was used, a monomer containing BPA in its structure, and EGDMA as crosslinker. In the semi-covalent imprinting strategy, BPA was then cleaved from the polymer by hydrolysis with tetrabutylammonium hydroxide (\(n\)-Bu\({}_{4}\)NOH), also in scCO\({}_{2}\). Both polymers were obtained as aggregates of discrete nanoparticles of smooth surface and as dry powders in high yields (>90%, determined gravimetrically). Non-covalent imprinted polymer could adsorb 450 umol-g\({}^{-1}\) from a BPA aqueous solution containing 300 umol-L\({}^{-1}\), while semi-covalent imprinted polymer could adsorb 98 umol-g\({}^{-1}\) from a BPA aqueous solution containing 50 um when static binding tests were performed in both polymers. Aspirin (AS) and acetaminophen (AAP)-imprinted polymers were prepared by [PERSON] et al. [30] in 2013. There is an increasing concern with aquatic environment pollution [31] by active pharmaceuticals which can cause potentially liver damage [32] and cancer [33]. In this work, MAA or 4-vinylpyridine (4-VPy) were used as monomers, methyl methacrylate (MMA) as third monomer, and EGDMA as a crosslinker by three different strategies: bulk, emulsion, and scCO\({}_{2}\)-assisted polymerization. Fine MIP particles with average size of 250-300 nm were obtained. 4-VPy-based polymer was shown to be more efficient in binding capacity, adsorbing larger amounts of templates and showing higher imprinting factor (IF) value. In this case, scCO\({}_{2}\)-assisted polymerization was shown to be more efficient at selectively separating and detecting templates than the other polymerization processes. BPA and 2,4-dichlorophenoxyacyacetic acid-imprinted polymers were also reported by [PERSON] et al. [34], in which MIPs were prepared by dispersion polymerization in scCO\({}_{2}\), using MAA as functional monomer, EGDMA as the crosslinker, and poly(heptadecafluorodecyl methacrylate) (PHDFDMA) as a dispersing agent, obtaining particles with 300 nm. BPA and 2,4-dichlorophenoxyacyacetic acid, an herbicide compound, are typically present in aqueous solutions. Both polymers confirmed their efficient binding properties. Carbamazepine (CMZ)-imprinted polymer was also synthesized by [PERSON] et al. [35] by dispersion polymerization in scCO\({}_{2}\), using MAA as functional monomer, EGDMA as the crosslinker, and PHDFDMA as a dispersion agent for selective separation of CMZ from aqueous solutions. CMZ is a drug broadly used to treat epilepsy and bipolar disorders which has also been found in effluent waters because of inefficient removal from wastewaters [36; 37]. For this reason, CMZ is becoming a hazard to health and environment, due to the difficulty to completely remove this compound from water. It easily reaches the surface water, and is discharged to other media when water is reused. These authors produced nano-sized fine imprinted particles and evaluated the effect of pH and temperature. pH 7 and 20 \({}^{\circ}\)C were the conditions where the CMZ adsorption was the highest. They showed that CMZ-imprinted polymer is suitable for the selective separation of CMZ from aqueous solutions. In 2014, labdanolic acid (LA)-imprinted polymer was reported by [PERSON] et al. [38] for use on the LA purification from the acidic crude oil of _C. ladaniferus_. LA is a natural product from a Portuguese natural resource, and can be potentially used in medicine due to its relevant biological properties, such as anti-mutagenic and anti-inflammatory properties [39].