Experimental and theoretical study of molecular interactions between 2-vinyl pyridine and acidic pharmaceuticals used as multi-template molecules in molecularly imprinted polymer
Graphical Abstract
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.
References (35)
- et al.
Polymer
(2011) - et al.
J. Chromatogr. A
(1999) - et al.
Anal. Chim. Acta
(2008) - et al.
J. Chromatogr. A
(2000) - et al.
J. Chromatogr. A
(2012) - et al.
Sensors Actuators B Chem.
(2015) - et al.
Spectrochim. Acta A Mol. Biomol. Spectrosc.
(2013) - et al.
J. Chromatogr. A
(2013) - et al.
Anal. Chim. Acta
(2005) - et al.
Water Res.
(2005)
Int. J. Hyg. Environ. Health
Sci. Total Environ.
Int. J. Pharm.
Talanta
J. Hazard. Mater.
Chem. Eng. J.
Biomaterials
Cited by (48)
Molecularly imprinted polymers: A closer look at the template removal and analyte binding
2024, Biosensors and BioelectronicsMolecular imprinting with deep eutectic solvents: Synthesis, applications, their significance, and benefits
2022, Journal of Molecular LiquidsDesign of molecularly imprinted polymer materials relying on hydrophobic interactions
2022, Colloids and Surfaces A: Physicochemical and Engineering AspectsCitation Excerpt :MIPs based on the acrylic acid functional monomer are widely studied because the weak carboxylic acid groups may bind by hydrogen bonds to many weakly basic compounds [1,4–7]. Many types of other functional monomers having hydrogen bonding ability have been considered [3,6–10]. Isotropic interactions such as electrostatic ones may be strong but their isotropic nature make them unspecific.