Rational design of salmeterol xinafoate imprinted polymer through computational method: Functional monomer and crosslinker selection

Abstract

A molecular imprinted polymer (MIP) was computationally designed and synthesized for the selective extraction of salmeterol xinafoate (SLX) from human serum. In this study, semi-empirical PM3 calculations were used to find a suitable functional monomer (FM), the ratio of template (T) to FM, and types of crosslinkers. MIPs were synthesized with 2-hydroxyethyl methacrylate (HEMA) with T:FM mol ratios of 1:6 and 1:4 and ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) as a crosslinker. On the basis of computational and experimental results, HEMA and TRIM in the mol ratio 1:6 of T-FM (MIP3) were found to be the best choices of FM and crosslinker, respectively. These polymers were then used as a selective sorbent to develop a molecularly imprinted solid-phase extraction procedure followed by high performance liquid chromatography with UV detection for the determination of SLX in serum. The extraction ability of MIP3 was excellent with a recovery of 92.17% ± 2.66% of SLX in spiked serum, and 91.15% ± 1.12% when SLX was spiked as a mixture with another analogous structure. By comparing the performance of the synthesized sorbent with a C-18 cartridge with a recovery of 79.11% ± 2.96%, it was determined that MIP had better performance over the latter. On the basis of these results, the imprinted receptor MIPs, especially MIP 3, can be applied for the direct extraction of SLX in clinical analysis.

Molecular Dynamic Study of Mechanism Underlying Nature of Molecular Recognition and the Role of Crosslinker in the Synthesis of Salmeterol-Targeting Molecularly Imprinted Polymer for Analysis of Salmeterol Xinafoate in Biological Fluid

“…MIP and NIP were synthesized using the precipitation polymerization method, as follows. MIP was obtained by dissolving SLX (1 mmol) as a template and HEMA as a functional monomer (4 mmol / 6 mmol) in 350 mL of an isopropanol:methanol (1:1) mixture, based on constant associations in a previous study [ 7 ] in sealed bottles, and then sonicated for 5 min. Subsequently, EGDMA/TRIM (20 mmol) was added to the solution as a crosslinker and then sonicated for 40 min.…”

“…The extraction was complete if there was no more absorbance from the template in the measurement with the microplate. Table S1 shows the composition of precipitation synthesized MIP and NIP in this work, with the same combination as our previous study [ 7 ].…”

“…The small concentrations of analyte target in complex matrices require selective sample preparation methods [ 6 ]. Molecularly imprinted polymers (MIPs) with the ability to recognize molecular targets can be used as novel sorbents for solid phase extraction to extract SLX from biological fluids [ 7 ]. MIP is a polymeric porous material with complementary binding features concerning the molecule’s structure, shape, and spatial orientation [ 8 ].…”

“…In a previous study [ 7 ], the molecular modeling approach and bulk polymerization method were employed to design and synthesize MIP for the analysis of SLX from spiked serum. A semi-empirical PM3 method was used to calculate the binding energy of the complex between the template–functional monomer and the template–crosslinker, to select the functional monomer with a stable interaction and the crosslinker with the weakest interaction with the template.…”

“…To support the molecular modeling result, in the present study, we used molecular dynamics simulations as this is a suitable method for describing the interaction of many components in a system containing a large number of molecules [ 37 ]. To improve the binding properties of the previous results [ 7 ], we used the precipitation polymerization method to synthesize the novel polymers. The precipitation method was expected to provide a smaller and homogenous particle size with a large surface area that would provide better conditions for optimum binding of SLX to the polymers [ 38 ].…”