In silico and experimental study of functionalized monomer for molecularly imprinted-enoxaparin polymer: A novel green approach

Abstract

Enoxaparin (enox) is a low molecular weight heparin. Enox, which has side effects of thrombocytopenia and bleeding, requires monitoring drug therapy. The analysis method of enox in the blood plasma matrix needs a prior separation method. There has not been a molecularly imprinted polymer (MIP) synthesis for enox in earlier studies. Therefore, a novel MIP of enox was synthesized via microwave synthesizer workstation. This research aims to examine the application of in silico studies in selecting functional monomers and their comparison with enoxaparin before carrying out MIP synthesis. Enox as a template was polymerized with itaconic acid (ITA) as the best functional monomer; N,N′-methylenebisacrylamide as a cross-linking agent; water as a porogen; and ammonium persulfate as an initiator. Itaconic acid was selected using the in silico to calculate binding energy, and Gibbs free energy gives the smallest values. Itaconic acid and enoxaparin ratio was computed using DFT, and GFN2-xTB found that 1:6 was the best ratio. For calculations using molecular dynamics simulations, it was found that a ratio of 1:1 was the best, the same as in laboratory experiments using the job's plot. Polymerization was performed using a microwave at room temperature (28 °C) with an ITA ratio of 1:1, 1:4, and 1:6. Nonimprinted polymers (NIP) were similarly prepared without a template as a control. All polymer particles were characterized by spectral (Fourier-transform infrared spectroscopy), thermal (thermogravimetric analysis–differential thermal gravimetry), and morphology (scanning electron microscope). The adsorption capacity for enox was carried out with MIP and NIP. The performance of MIP was evaluated by determining the imprinting factors calculated. The MIP 1:1, 1:4, and 1:6 displayed imprinting factor is 1.21, 0.68, and 0.68, respectively. The best ratio of ITA to Enox is 1:1.