Preparation of Methacrylate-based Polymers Modified with Chiral Resorcinarenes and Their Evaluation as Sorbents in Norepinephrine Microextraction

Abstract

Aminomethylation reactions between chiral amino compounds (S)-(-)-1-phenylethylamine and l-proline with tetranonylresorcinarene and tetra-(4-hydroxyphenyl)resorcinarene in presence of formaldehyde were studied. The reaction between l-proline and resorcinarenes generated regioselectively chiral tetra-Mannich bases, due to the molecular incorporation of the fragment of the chiral amino acid. On the other hand, tetranonylresorcinarene and (S)-(-)-1-phenylethylamine formed regio- and diasteroselectively chiral tetrabenzoxazines, both by chiral auxiliary functionalization and by the transformation of the molecular structure that confers inherent chirality. The products obtained were characterized using IR, ¹H-NMR, ¹³C-NMR, COSY, HMQC, and HMBC techniques. The reaction of (S)-(-)-1-phenylethylamine with tetra-(4-hydroxyphenyl)resorcinarene did not proceed under the experimental conditions. Once the chiral aminomethylated tetra-(4-hydroxyphenyl)resorcinarene was obtained, the chemical modification of poly(GMA-co-EDMA) was studied, and the results showed an efficient incorporation of the aminomethylated compound. For the physical modification, chiral aminomethylated tetranonylresorcinarenes were employed, finding that the incorporation of modified resorcinarenes occurs, but with less efficiency than that observed using chemical modification. The modified polymers were characterized via FT-IR, scanning electron microscopy imaging, and elemental analysis. Finally, polymers modified with chiral resorcinarenes were used as sorbents in norepinephrine microextraction; for practical purposes, artificial urine was prepared and used. To perform the microextraction, the decision was made to use the modern rotating-disk sorptive extraction technique (RDSE), because of its analytical attributes as a green, or eco-friendly, technique. According to the results, the method preliminarily validated for the determination of norepinephrine in artificial urine shows that the modified polymer with chiral derivative of tetra-(4-hydroxyphenyl)resorcinarene worked effectively as a new sorbent phase for the quantitative microextraction of norepinephrine, exhibiting high stability and homogeneity of composition and structure within the working range.

Keywords: Chiral resorcinarene; aminomethylation; microextraction; norepinephrine.

Figure 1

Structure of L-norepinephrine.

Scheme 1

Preparation of polymers 1 and 2.

Scheme 2

Synthesis of chiral resorcinarenes 5–7.

Figure 2

¹H-NMR spectra (400 MHz, DMSO-d₆, 323 K) of compound 6. (a) Conventional, (b) adding D₂O, and (c) suppressing the residual signal of D₂O.

Scheme 3

Chemical modification of poly(GMA-co-EDMA) (1) with chiral resorcinarene 7.

Figure 3

Characterization of the modified polymer 7-poly(GMA-co-EDMA) (8) (red) in comparison with the unmodified polymer 1 (black). (a) ATR-FT-IR spectra. (b) Raman spectra. (c) Thermogravimetric analysis (TGA) thermograms and curve dm/dT of 8 (blue). Scanning electron micrographs at 2 μm, (d) 1 and (e) 8.

Scheme 4

Chemical modification of poly(GMA-co-EDMA) (1) with chiral resorcinarene 7.

Figure 4

Comparison of the analytical signal (area) of norepinephrine, after the rotary disk sorption extraction technique (RDSE) microextraction, using polymers 1, 2, 8∓10 as sorbents, in artificial urine fortified at 1000 μgL⁻¹.

Figure 5

Standardized Pareto chart of the experimental design of the screening.

Figure 6

Standardized Pareto chart of the experimental design of the optimization.

Figure 7

Response surface of the experimental optimization design.