Design of a New Molecularly Imprinted Polymer Selective for Hydrochlorothiazide Based on Theoretical Predictions Using Gibbs Free Energy

Leonardo A Barros,Susanne Rath,Rogério Custodio

doi:10.5935/0103-5053.20160126

Leonardo A Barros, Susanne Rath + Show 1 more

Open Access

https://doi.org/10.5935/0103-5053.20160126

Copy DOI

Abstract

A molecularly imprinted polymer (MIP) for the diuretic drug hydrochlorothiazide (HCTZ) based on theoretical predictions was developed. Molecular modeling calculations were performed to study the intermolecular interactions in the pre-polymerization mixture and to select a suitable functional monomer and a porogenic solvent for the synthesis of the MIP. To confirm the results of the theoretical predictions, three MIPs were synthesized and evaluated using the equilibrium batch rebinding method. A water-compatible MIP was prepared using HCTZ as the template and acrylamide as the functional monomer (FM) with ethylene glycol dimethacrylate as the cross-linker and tetrahydrofuran as the porogen. An imprinting factor of 8.24 was obtained. The polymer was characterized by Fourier transform infrared (FTIR), solid-state nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis and nitrogen sorption porosimetry. In addition to HCTZ, six structurally related compounds were tested to evaluate the selectivity of the HCTZ-MIP, and cross-selectivity of the MIP was verified.

Highlights

In order to predict the properties of the molecularly imprinted polymer (MIP) at the molecular level, the conformations of HCTZ, the functional monomer (FM) and FM-HCTZ complexes were optimized to the lowest energy level using the Density functional theory (DFT) method, the B3LYP/6-31G(d) level of theory
The following FMs were selected for theoretical evaluations: methacrylic acid (MAA), acrylic acid (AA), 2-(trifluoromethyl)acrylic acid (TFMAA), acrylamide (AAM), methacrylamide (MAAM), 4-vinylpyridine (4-VP) and allylamine (ALLY)
Our results showed that molecular modeling is a rational and rapid theoretical approach for the selection of appropriate conditions with regard to the FM and the porogenic solvent for successful molecular imprinting

Summary

Introduction

Molecular imprinting is a technique that creates recognition sites that are specific for a target molecule, called a template, within a synthetic polymer, and it has been widely used for the selective adsorption of drugs and their metabolites for analytical purposes.[1,2,3,4] Comparable to immunosorbents, the specific binding sites are assigned to the specific interactions between the template and the functional groups in the polymer network, acting to an antigen-antibody system.[5,6,7]. The synthesis of a MIP first involves the complexation in solution of a template with a functional monomer (FM) through non-covalent or covalent interactions, followed by the polymerization of these monomers around the template in the presence of a cross-linker, a radical initiator and an appropriate solvent. The FM that can interact most strongly with the template provides the most stable complex.[8]

Objectives

Methods

Results

Conclusion