MIP Synthesis by Precipitation Polymerization Technique

A Novel Molecular Imprint Polymer Synthesis for Solid Phase Extraction of Andrographolide


Hemavathi Krishnan(1*), A.K.M. Shafiqul Islam(2), Zainab Hamzah(3), Pubalan Nadaraja(4), Mohd Noor Ahmad(5)

(1) Department of Chemical Engineering Technology, Universiti Malaysia Perlis, Uniciti Alam Campus, Sungai Chuchuh, 02100 Padang Besar, Perlis, Malaysia
(2) Department of Chemical Engineering Technology, Universiti Malaysia Perlis, Uniciti Alam Campus, Sungai Chuchuh, 02100 Padang Besar, Perlis, Malaysia
(3) Department of Chemical Engineering Technology, Universiti Malaysia Perlis, Uniciti Alam Campus, Sungai Chuchuh, 02100 Padang Besar, Perlis, Malaysia
(4) Centre of Diploma Studies, Universiti Malaysia Perlis, Uniciti Alam Campus, Sungai Chuchuh, 02100 Padang Besar, Perlis, Malaysia
(5) Department of Electrical and Electronics, British Malaysian Institute, Universiti Kuala Lumpur, 53100 Gombak, Selangor, Malaysia
(*) Corresponding Author


The use of molecularly imprinted polymers for Solid phase micro-extraction (SPME) of bioactive compounds are getting popularity. The interest on efficient extraction process of andrographolide from the plant is increasing due to their vast therapeutic applications. In this study, andrographolide imprinted MIP was prepared by precipitation polymerization method using the non-covalent technique to use as sorbent materials for solid phase extraction of the bioactive compound. HyperChem 8.0.10 software was used to investigate and optimize the template and functional monomer ratio in the pre-polymerization system to synthesize the imprinted polymers. Molecular modeling gives information about molecular interactions and the Gibbs free energies of the pre-polymerization complex. Based on the computational study, andrographolide, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were used as the template, functional monomer, and cross-linker, respectively at the 1:3:20 ratios. The MIPs were characterized by kinetic study and imprinting factor. The binding parameters for the recognition of andrographolide were studied using Langmuir, Freundlich and Langmuir-Freundlich adsorption isotherm models. Andrographolide MIP contains the maximum number of binding sites with the adsorption capacity of 149.59 μg/g. The SPME experimental data best fit with Langmuir-Freundlich isotherm model with the R2 value of 0.997. This research shows that the MIPs prepared by precipitation polymerization gives a good extraction capability using SPME method.


Andrographolide; molecularly imprinted polymer; precipitation polymerization; adsorption isotherm

Full Text:

Full Text PDF


[1] Thakur, A.K., Chatterjee, S.S., and Kumar, V., 2015, Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata), J. Tradit. Complement. Med., 5 (1), 42–50.

[2] Wen, L., Xia, N., Chen, X., Li, Y., Hong, Y., Liu, Y., Wang, Z., and Liu, Y., 2014, Activity of antibacterial, antiviral, anti-inflammatory in compounds andrographolide salt, Eur. J. Pharmacol., 740, 421–427.

[3] Okhuarobo, A., Falodun, J.E., Erharuyi, O., Imieje, V., Falodun, A., and Langer, P., 2014, Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: A review of its phytochemistry and pharmacology, Asian Pac. J. Trop. Dis., 4 (3), 213–222.

[4] Jada, S.R., Subur, G.S., Matthews, C., Hamzah, A.S., Lajis, N.H., Saad, M.S., Stevens, M.F.G., and Stanslas, J., 2007, Semisynthesis and in vitro anticancer activities of andrographolide analogues, Phytochemistry, 68 (6), 904–912.

[5] Pandeti, S., Sonkar, R., Shukla, A., Bhatia, G., and Tadigoppula, N., 2013, Synthesis of new andrographolide derivatives and evaluation of their antidyslipidemic, LDL-oxidation and antioxidant activity, Eur. J. Med. Chem., 69, 439–448.

[6] Rao, Y.K., Vimalamma, G., Rao, C.V., and Tzeng, Y.M., 2004, Flavonoids and andrographolides from Andrographis paniculata, Phytochemistry, 65 (16), 2317–2321.

[7] Song, Y.X., Liu, S.P., Jin, Z., Qin, J.F., and Jiang, Z.Y., 2013, Qualitative and quantitative analysis of Andrographis paniculata by rapid resolution liquid chromatography/time-of-flight mass spectrometry, Molecules, 18 (10), 12192–12207.

[8] Wang, B., Li, J., Huang, W.L., Zhang, H.B., Qian, H., and Zheng, Y.T., 2011, Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents, Chin. Chem. Lett., 22 (7), 781–784.

[9] Chen, H., Ma, Y.B., Huang, X.Y., Geng, C.A., Zhao, Y., Wang, L.J., Guo, R.H., Liang, W.J., Zhang, X.M., and Chen, J.J., 2014, Synthesis, structure-activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents, Bioorg. Med. Chem. Lett., 24 (10), 2353–2359.

[10] Seniya, C., Shrivastava, S., Singh, S., and Khan, G.J., 2014, Analyzing the interaction of a herbal compound Andrographolide from Andrographis paniculata as a folklore against swine flu (H1N1), Asian Pac. J. Trop. Dis., 4 (Suppl. 2), S624–S630.

[11] Ji, L., Zheng, Z., Shi, L., Huang, Y., Lu, B., and Wang, Z., 2015, Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation, Biochim. Biophys. Acta, Gen. Subj., 1850 (4), 750–758.

[12] Hafid, A.F., Utsubo, C.A., Permanasari, A.A., Adianti, M., Tumewu, L., Widyawaruyanti, A., Wahyuningsih, S.P.A., Wahyuni, T.S., Lusida, M.I., Soetjipto., and Hotta, H., 2017, Antiviral activity of the dichloromethane extracts from Artocarpus heterophyllus leaves against hepatitis C virus, Asian Pac. J. Trop. Biomed., 7 (7), 633–639.

[13] Wongkittipong, R., Prat, L., Damronglerd, S., and Gourdon, C., 2004, Solid-liquid extraction of andrographolide from plants - Experimental study, kinetic reaction and model, Sep. Purif. Technol., 40 (2), 147–154.

[14] Majee, C., Gupta, B.K., Mazumder, R., and Chakraborthy, G.S., 2011, HPLC method development and characterization of bio-active molecule isolated from Andrographis paniculata, Int. J. PharmTech Res., 3 (3), 1586–1592.

[15] Kumar, S., Dhanani, T., and Shah, S., 2014, Extraction of three bioactive diterpenoids from Andrographis paniculata: Effect of the extraction techniques on extract composition and quantification of three andrographolides using high-performance liquid chromatography, J. Chromatogr. Sci., 52 (9), 1043–50.

[16] Ahmadi, F., Yawari, E., and Nikbakht, M., 2014, Computational design of an enantioselective molecular imprinted polymer for the solid phase extraction of S-warfarin from plasma, J. Chromatogr. A, 1338, 9–16.

[17] Islam, A.K.M.S., Krishnan, H., Singh, H., and Ahmad, M.N., 2015, A noble molecular imprint polymer biosensor for caffeic acid detection in orthosiphon Stamineus extracts, Jurnal Teknologi, 77 (7), 97–101.

[18] Krishnan, H., Islam, A.K.M.S., Hamzah, Z., and Ahmad, M.N., 2017, Rational computational design for the development of Andrographolide Molecularly Imprinted Polymer, AIP Conf. Proc., 1891 (1), 020083.

[19] Nicholls, I.A., Andersson, H.S., Golker, K., Henschel, H., Karlsson, B.C.G., Olsson, G.D., Rosengren, A.M., Shoravi, S., Suriyanarayanan, S., Wiklander, J.G., and Wikman, S., 2011, Rational design of biomimetic molecularly imprinted materials: Theoretical and computational strategies for guiding nanoscale structured polymer development, Anal. Bioanal. Chem., 400 (6), 1771–1786.

[20] Pardeshi, S., Dhodapkar, R., and Kumar, A., 2014, Molecularly imprinted microspheres and nanoparticles prepared using precipitation polymerisation method for selective extraction of gallic acid from Emblica officinalis, Food Chem., 146, 385–393.

[21] Pardeshi, S., and Singh, S. K., 2016, Precipitation polymerization: a versatile tool for preparing molecularly imprinted polymer beads for chromatography applications, RSC Adv., 6 (28), 23525–23536.

[22] Tahir, I., Ahmad, M.N., Islam, A.K.M.S., and Arbain, D., 2012, Virtual searching of dummy template for Sinensetin based on 2D molecular similarity using Chemdb tool, Indones. J. Chem., 12 (3), 217–222.

[23] Saputra, A., Wijaya, K., Armunanto, R., Tania, L., and Tahir, I., 2017, Determination of effective functional monomer and solvent for R(+)-cathinone imprinted polymer using density functional theory and molecular dynamics simulation approaches, Indones. J. Chem., 17 (3), 516–522.

[24] Yin, X., Liu, Q., Jiang, Y., and Luo, Y., 2011, Development of andrographolide molecularly imprinted polymer for solid-phase extraction, Spectrochim. Acta, Part A, 79 (1), 191–196.

[25] Tahir, I., Wijaya, K., Islam, S., and Ahmad, M.N., 2014, Computer aided design of molecular imprinted polymer for selective recognition of capsaicin, Indones. J. Chem., 14 (1), 85–93.

[26] Liu, W., Qin, L., Yang, Y., Liu, X., and Xu, B., 2014, Synthesis and characterization of dibenzothiophene imprinted polymers on the surface of iniferter-modified carbon microspheres, Mater. Chem. Phys., 148 (3), 605-613.

[27] Saad, E.M., Madbouly, A., Ayoub, N., and El Nashar, R.M., 2015, Preparation and application of molecularly imprinted polymer for isolation of chicoric acid from Chicorium intybus L. medicinal plant, Anal. Chim. Acta, 877, 80–9.

[28] Pardeshi, S., Patrikar, R., Dhodapkar, R., and Kumar, A., 2012, Validation of computational approach to study monomer selectivity toward the template gallic acid for rational molecularly imprinted polymer design, J. Mol. Model., 18 (11), 4797–4810.

[29] Liang, D., Wang, Y., Li, S., Li, Y., Zhang, M., Li, Y., Tian, W., Liu, J., Tang, S., Li, B., and Jin, R., 2016, Study on dicyandiamide-imprinted polymers with computer-aided design, Int. J. Mol. Sci., 17 (11), 1750.

[30] Nezhadali, A., Senobari, S., and Mojarrab, M., 2016, 1,4-Dihydroxyanthraquinone electrochemical sensor based on molecularly imprinted polymer using multi-walled carbon nanotubes and multivariate optimization method, Talanta, 146, 525–532.

[31] Mancin, F., 2017, The strength of the interaction, http://www.chimica.unipd.it/fabrizio.mancin/pubblica/Suprachem/II%20lezione%20Mancin.pdf, 1–32.

[32] Khan, M.S., Wate, P.S., and Krupadam, R. J., 2012, Combinatorial screening of polymer precursors for preparation of benzo-pyrene imprinted polymer: An ab initio computational approach, J. Mol. Model., 18 (5), 1969–1981.

DOI: https://doi.org/10.22146/ijc.34369

Article Metrics

Abstract views : 1404 | views : 459

Copyright (c) 2019 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.


Indonesian Journal of Chemisty (ISSN 1411-9420 / 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Analytics View The Statistics of Indones. J. Chem.