Design and Optimization of Molecularly Imprinted Polymer Targeting Epinephrine Molecule: A Theoretical Approach

Abstract

Molecularly imprinted polymers (MIPs) are a growing highlight in polymer chemistry. They are chemically and thermally stable, may be used in a variety of environments, and fulfill a wide range of applications. Computer-aided studies of MIPs often involve the use of computational techniques to design, analyze, and optimize the production of MIPs. Limited information is available on the computational study of interactions between the epinephrine (EPI) MIP and its target molecule. A rational design for EPI-MIP preparation was performed in this study. First, density functional theory (DFT) and molecular dynamic (MD) simulation were used for the screening of functional monomers suitable for the design of MIPs of EPI in the presence of a crosslinker and a solvent environment. Among the tested functional monomers, acrylic acid (AA) was the most appropriate monomer for EPI-MIP formulation. The trends observed for five out of six DFT functionals assessed confirmed AA as the suitable monomer. The theoretical optimal molar ratio was 1:4 EPI:AA in the presence of ethylene glycol dimethacrylate (EGDMA) and acetonitrile. The effect of temperature was analyzed at this ratio of EPI:AA on mean square displacement, X-ray diffraction, density distribution, specific volume, radius of gyration, and equilibrium energies. The stability observed for all these parameters is much better, ranging from 338 to 353 K. This temperature may determine the processing and operating temperature range of EPI-MIP development using AA as a functional monomer. For cost-effectiveness and to reduce time used to prepare MIPs in the laboratory, these results could serve as a useful template for designing and developing EPI-MIPs.

Keywords: epinephrine; molecular dynamic simulation; molecular interactions; molecularly imprinted polymers; solubility; stability.

Scheme 1

A general workflow of the simulation methods that was adopted.

Figure 1

Plots displaying frontier molecular orbitals from ground state density surface.

Figure 2

The optimized geometry structures of the reacting species: (a) Mulliken charges and (b) molecular electrostatic potential surfaces (the proton accepting and proton donating sites of molecules are electrostatically marked in red and blue color, respectively).

Figure 3

The optimized structures of the generated complexes between EPI and monomers with Mulliken charges.

Figure 4

(a) Binding energies calculated for the complexes between the template and the monomers in the gas phase by DFT using various functionals and basis sets (b) Binding energies of the resulting complexes formed between the template and the monomers in different porogenic solvents using the B3LYP/6-31g method.

Figure 5

The Flory–Huggins parameters: (a) chi and (b) mixing energy for template–monomer miscibility analysis.

Figure 6

Free energy and temperature effect on EPI–monomer miscibility: (a) 293 K, (b) 303 K, (c) 313 K.

Figure 7

The optimum simulated amorphous cell for EPI–monomer–EGDMA–acetonitrile. EPI (orange), EGDMA (red), and acetonitrile (the stick molecules): (a) EPI-4VP (4VP, green), (b) EPI-AA (AA, purple), (c) EPI-ANI (ANI, light green), (d) EPI-GMA (GMA, light blue), (e) EPI-HEMA (HEMA, blue), and (f) EPI-MAA (MAA, pink).

Figure 8

(a) Solubility parameters (δ) for EPI–monomer complexes, (b) equilibrium energies, and (c) potential energy components for different ratios of EPI-AA complexes.

Figure 9

The plot of (a) specific volume, (b) density, (c) mean square displacement (MSD), (d) intensity, (e) equilibrium energies, and (f) radius of gyration (Rg) versus temperature for EPI-AA at a ratio of 1:4.