Magnetic Molecularly Imprinted Polymer for Selective Trapping - MIPTRAP

Axe Application - Chimie de la santé

Projet de recherche mené de novembre 2017 à novembre 2018.

Laboratoires co-porteurs
Mots clés 

Alternative magnetic field, dynamic kinetic resolution, magnetic nanoparticles, molecularly imprinted polymer

Abstract

The concept described here consists of Magnetic Molecularly Imprinted Polymers (MIPs) (labelled as Fe2O3@MIP-Sphen nanoparticles) as a selective enantiomer traps. Fe2O3@MIP-Sphen nanoparticles were assessed as a new standard/dynamic kinetic resolution (KR) system in which one enantiomer (S-phenylethanol) was trapped selectively by the magnetic MIPs and after isolation of the nanoparticles, was released quantitatively under alternating magnetic field (AMF) (Scheme 1).

Scheme 1. Application of magnetic MIP for standard/dynamic kinetic resolution.
Scheme 1. Application of magnetic MIP for standard/dynamic kinetic resolution.
Design of magnetic MIP nanoparticles for asymmetric resolution of 1-phenylethanol

The maghemite (Fe2O3) NPs were first synthesized through a coprecipitation method, followed by a size sorting process through salt destabilization to get the largest NPs, most efficient for magnetic hyperthermia. TEM analysis showed particles with an average particle diameter (d0) of 11 nm and a polydispersity ??? of 0.23. To functionalize the Fe2O3 MNPs, TTMA functions were anchored by complexation with iron ions at the nanoparticle surface in methanol. Then, the polymerization could proceed, mixing Fe2O3@TTMA nanoparticles with MA as the functional monomer, EGDMA as the crosslinking agent, Sphen as template, and AIBN as the polymerization initiator in methanol. The deoxygenated mixture was then placed at 70°C during 16h. Afterwards, soxhlet extraction was carried out to remove the template (S-phen) at 80°C with 300 ml of methanol-acetic acid (90:10, v/v). Finally, the nanoparticles (labeled as Fe2O3@MIP-Sphen) were washed in a methanol/acetic acid (9:1) mixture to eliminate S-phen. (Scheme 2)

Scheme 2. Synthesis of Fe2O3@MIP-Sphen via a subsequent grafting of methacrylic acid
Scheme 2. Synthesis of Fe2O3@MIP-Sphen via a subsequent grafting of methacrylic acid

The polymer layer for Fe2O3@MIP-Sphen nanoparticles was too thin to appear on the TEM images, however no morphological change or aggregation is observed due to polymerization process. (Figure 1)

Figure1. TEM image of Fe2O3@MIP-Sphen
Figure1. TEM image of Fe2O3@MIP-Sphen

The MIP shell of Fe2O3@MIP-Sphen was evidenced by IR spectroscopy with the presence of new peaks after polymerization detected at 2904 and 1746 cm?1 attributed, respectively, to the presence of CH2 and C=O groups. (Figure 2)

Figure2. FTIR spectrum of Fe2O3@MIP-Sphen
Figure2. FTIR spectrum of Fe2O3@MIP-Sphen

Thermogravimetric analysis (TGA) showed that the amount of MIP on Fe2O3@MIP-Sphen was about 60% of the total particle weight, as determined from the significant mass change between 270 and 400°C owing to decomposition of MIP

Figure 3. TGA thermogram of Fe2O3@MIP-Sphen
Figure 3. TGA thermogram of Fe2O3@MIP-Sphen

Fe2O3@MIP-Sphen nanoparticles for standard/kinetic kinetic resolution

We first assessed the activity of Fe2O3@MIP-Sphen nanoparticles in standard kinetic resolution (SKR), validating the principle of release under AMF stimulation (Scheme 3).

Scheme 3. Fe2O3@MIP-Sphen nanoparticles in standard kinetic resolution (SKR)
Scheme 3. Fe2O3@MIP-Sphen nanoparticles in standard kinetic resolution (SKR)

Then, the system was combined with an appropriate racemization method for dynamic kinetic resolution (DKR) approach. In-situ racemization of R-enantiomer was achieved by a transition-metal complex (Ruthenium, Iridium), as it is illustrated in Scheme 4.

The project started  in November 2018 and we are improving this last step consisting on the racemization of the R-enantiomer. 

We contacted Marie-Odile Lafon to deposit a patent before the end of June.

Additionally, the LABEX MiChem financed the presentation of a poster for Maria Nerantzaki in BPC2018 (from 28 to 31 of may).

Chromatograms of S-phenylethanol R-phenylethanol and the racemic micture.