Experimental and theoretical study of molecular interactions between 2-vinyl pyridine and acidic pharmaceuticals used as multi-template molecules in molecularly imprinted polymer

https://doi.org/10.1016/j.reactfunctpolym.2016.03.017Get rights and content

Abstract

Molecular interactions between functional monomer and template molecules are regarded as the driving force for the success of a molecularly imprinted polymer. In this study, a multi-template molecularly imprinted polymer (MIP) for ibuprofen, naproxen and diclofenac was synthesized in an oil bath set at 70 °C for 24 hours. 2-vinyl pyridine, ethylene glycol dimethacrylate, toluene and 1,1-azobis-(cyclohexanecarbonitrile) were used as functional monomer, cross-linker, porogen and radical initiator, respectively. A non-imprinted polymer (NIP) was synthesized using a similar approach with the omission of templates. Monomer-template interactions were examined using Molecular Dynamics and Fourier Transform Infrared Spectroscopy (FTIR). Both molecular dynamics and FT-IR results indicated the formation of the hydrogen bond between the templates and 2-vinyl pyridine. Molecular dynamics further revealed the identity of the hydrogen atoms in the templates involved in interactions with nitrogen atom on the functional monomer in the presence of toluene molecules. Surface area obtained for the MIP using Brunauer, Emmett and Teller method was 282 m2/g, whereas 232 m2/g was obtained for the NIP. This indicated that MIP has more binding sites compared to the NIP. Furthermore, batch adsorption and selectivity experiments were carried out in the presence of gemfibrozil as the competitor. When such experiments were carried out in toluene, the adsorption capacities (mg/g) obtained for naproxen, ibuprofen, diclofenac and gemfibrozil were 14.4, 11.0, 14.0 and 7.5, respectively. These results show that the MIP was more selective to the compounds that were used as template molecules.

Introduction

Molecular imprinting is a technique that is used to prepare polymers with highly specific binding sites for small molecules [1]. Molecularly imprinted polymers (MIPs) are prepared using a functional monomer(s), which allows the interactions with the functional group(s) of a molecule to be recognized and they are synthesized with a cross linking monomer(s) in the presence of the target molecule(s). The imprint molecule(s) is removed from the polymer in order to create the molecularly imprinted complementary binding site(s) for the target molecule(s) [2]. Over the last two decades, molecularly imprinted polymers have gained several scientific applications that includes their use as; solid-phase extraction sorbents [3], chromatographic stationary phase [4], [5], [6], electrochemical sensor [7], etc. The popularity of MIPs in chemistry applications is attributed to their properties that include high selectivity, mechanical strength, and resistance against acids, bases, organic solvents, high pressures and temperatures [8].

Acidic pharmaceuticals such as ibuprofen, diclofenac and naproxen (organic structures shown in Fig. 1 (a) – (c)) belong to the class of non-steroidal anti-inflammatory drugs. They are among the group of pharmaceutical compounds that is often used to promote human health [9]. Once used by humans, they are excreted during urinary discharges as free drugs or as metabolites. This contributes to the presence of the acidic pharmaceuticals in the influent and effluent of wastewater treatment plants at the low μg/L levels [10], [11], [12]. Amdany et al. [12] reported the concentration range of 52 to 128 μg/L for naproxen, ibuprofen and triclosan in wastewater influent, whereas, 11 to 25 μg/L was reported for the same compounds in the effluent. A group of acidic pharmaceuticals have been also detected simultaneously in aquatic environment that includes river water and drinking water at ng/L levels [13], [14].

Recent methods that are used for the quantitative determination of acidic compounds in aqueous matrices involves the use of MIPs for the selective extraction and/or pre-concentration of target compounds [15], [16], [17]. In this regard, multi-template MIPs are of great importance as they are able to selective extract a group of acidic pharmaceuticals. 2-vinyl pyridine (functional monomer) shown in Fig. 1 (d) and ethylene glycol dimethacrylate (cross-linker) are widely used in the synthesis of MIP that is imprinted with ibuprofen, diclofenac or naproxen [18], [19]. Functional monomer and ethylene glycol dimethacrylate form polymer matrix around the template thus preserving monomer-template binding sites [1]. Functional monomers are understood to be responsible for the binding interactions in the imprinted binding sites. During the imprinting process, the functionality of the template is matched with that of the functional monomer [20].

Molecular interactions that occur between the functional monomer and template molecules have been previously explained using spectroscopic techniques such as nuclear magnetic resonance (NMR), ultraviolet-visible (UV-Vis) and Fourier transform infrared spectroscopy FT-IR [21], [22]. For example, Farrington and Regan [23] have used density functional theory and NMR to demonstrate the interactions that take place between 2-vinyl pyridine and ibuprofen. However, factors that might influence the interactions between 2-vinyl pyridine and acidic pharmaceuticals have not been thoroughly investigated. Despite having a detailed literature for the investigation of monomer-template interactions for the MIP synthesized for acidic pharmaceuticals, the influence of a porogenic solvent during the molecularly imprinting process have not been addressed in details. Insight into monomer-template interactions have been investigated by Lasagabaster-Latorre et al. [24]. In their study, they investigated the interactions that occur between 4-vinyl pyridine (functional monomer) and Bisphenol A (template) using spectroscopic techniques such as UV-Vis, proton NMR and FT-IR.

However, this study investigate the molecular interactions of 2-vinyl pyridine with three acidic pharmaceuticals that have been simultaneously imprinted. FT-IR being the traditional technique that is widely used for functional group characterization is applied in this study alongside the molecular dynamics for gaining insight into molecular interactions that occur between 2-vinyl pyridine and acidic pharmaceuticals. This study further shows that the solvent used during the template re-binding affects the adsorption of target compounds into MIP particles. The objective of this study was to investigate the interactions that occur between 2-vinyl pyridine and acidic pharmaceuticals by employing the spectroscopic techniques in parallel with the molecular dynamics. The selectivity of the polymers synthesized in this study was further studied using a structurally related acidic pharmaceutical as the competitor.

Section snippets

Chemicals

Naproxen (98 %), ibuprofen (≥ 98 %), diclofenac sodium salt, 2-vinylpyridine (97 %), 1,1’-azobis-(cyclohexanecarbonitrile) (98 %), ethylene glycol dimethacrylate (98 %), HPLC grade acetone (≥ 99.8 %), HPLC grade chloroform (≥ 99.8 %) and toluene (99.7 %) were purchased from Sigma-Aldrich (Steinheim, Germany). HPLC-grade acetonitrile (≥ 99.9 %) and glacial acetic acid (100 %) were purchased from Merck (Darmstadt, Germany). Formic acid (approx. 98 %) was purchased from Fluka (Steinheim, Germany).

Synthesis of polymers

Monomer-template interactions - Molecular dynamics simulation

The Mulliken charges of all the atoms present in the functional monomer and all template molecules are recorded in Table 1(a) – (d). These charges were used to predict the atoms that are most likely to form hydrogen bonding [28]. Based on these charges, it was found that the possible proton donors for ibuprofen, diclofenac and naproxen were H20, H30 and H31, respectively while on the other hand N3 for 2-vinyl pyridine was the most likely candidate for proton acceptor. It was also noted that H24

Conclusion

A multi-template molecularly imprinted polymer was synthesized and characterized. It was evident from FT-IR characterization that both MIP and NIP have a similar backbone structure. Higher surface area was obtained for the MIP and that translated to the MIP being the polymer that have higher adsorption capacity than the NIP. BET results further indicated that both MIP and NIP have mesoporous structures. SEM images showed that the surface of the MIP was rough and irregular when compared to the

Acknowledgements

This work is based on the research supported in part by the National Research Foundation (NRF) of South Africa for the grant, Unique Grant No. 93986. NRF and Durban University of Technology are thanked for funds allocated for lecturer replacement of Lawrence Mzukisi Madikizela.

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