本研究以磺胺二甲嘧啶 (Sulfamethazine, SMZ) 為模板分子，四甲氧基矽烷(Tetramethoxysilane, TMOS) 和一甲基三甲氧基矽烷 (Methyltrimethoxysilane, MTMOS) 為單體，經溶膠-凝膠程序製備無機分子拓印高分子 (inorganic molecularly imprinted polymer, IMIP) 。所討論的變數為 (1) 反應系統的R值 (H2O/Si molar ratio) (2) 競爭吸附實驗中標準溶液pH值 (3) 鍛燒溫度 (4) TMOS之比例 (5) HCl添加量 (6) 系統反應溫度，最後再以高效能液相層析儀 (high performance liquid chromatographic method, HPLC) 測量SMZ與相似物磺胺甲噁唑 (Sulfamethoxazole, SMO) 濃度進而算出吸附量與選擇率。
結果顯示當競爭吸附實驗中標準溶液pH值接近模板分子的pKa2值時(pH=7.4) 可有效提高選擇率。其中IMIP之SMZ吸附量會隨著R值和第二階段鍛燒溫度上升而增加。TMOS之比例會影響無機網目的交聯密度和柔軟性，最後再適當改變HCl添加量和反應溫度。結果顯示當標準溶液pH值為7.4， R值為10，第二階段鍛燒溫度為375℃，TMOS比例為1， HCl添加量為750 μl和反應溫度為80℃下，可獲得最高的選擇率 (α=21.8) 且辨識效果比無拓印高分子 (non-imprinted polymer, NIP) 更佳。

Inorganic molecularly imprinted polymer (IMIP) based on tetramethoxysilane (TMOS) and methyltrimethoxysilane (MTMOS) by sol-gel process has been developed. The conditions of preparation, the ratio of water to monomers (R), pH value of competition solution, calcination temperature, the ratio of TMOS to monomers (TMOS ratio), amount of hydrochloric acid and the reaction temperature were investigated. The competition experiment of the IMIP for template (sulfamethazine, SMZ) and analogue(sulfamethoxazole, SMO) were analyzed by High-Performance Liquid Chromatography (HPLC).
The results showed that the higher selectivity of IMIP was obtained when pH value of competition solution was set to the pKa2 of SMZ. In addition, the adsorption of SMZ was increased with increase of the R value and the 2nd step calcination temperature. The crosslink and flexible of network were affected by TMOS ratio. Finally, amount of hydrochloric acid and the reaction temperature were also adjusted appropriately. The results showed that the best selectivity (α=21.8) of IMIP were obtained with R=10, the pH value of competition solution = 7.4, TMOS ratio = 1, amount of hydrochloric acid was 750 μl, the reaction temperature = 80℃ and the 2nd step calcination temperature =375°C. The IMIP (AdSMZ=2.18 μmol/g, α=21.8) was obtained the more efficiency than non-imprinted polymer (AdSMZ=1.62 μmol/g, α=6.23).

1. Fischer, E.,“Einfluss der configuration auf die wirkung derenzyme”, Chem. Ber., Vol.27, pp. 2985-1993, 1894
2. Ramstrom, O., L.I. Andersson, and K. Mosbach,“RECOGNITION SITES INCORPORATING BOTH PYRIDINYL AND CARBOXY FUNCTIONALITIES PREPARED BY MOLECULAR IMPRINTING”, Journal of Organic Chemistry, Vol.58, pp. 7562-7564, 1993
3. L.Pauling,“A Theory of the Structure and Process of Formation of Antibodies”, Journal of the American Chemical Society Vol.62, pp. 2643-2657, 1940
4. Ye, L., I. Surugiu, and K. Haupt,“Scintillation proximity assay using molecularly imprinted microspheres”, Analytical Chemistry, Vol.74, pp. 959-964, 2002
5. Marx, S., et al.,“Parathion sensor based on molecularly imprinted sol-gel films”, Analytical Chemistry, Vol.76, pp. 120-126, 2004
6. Hillberg, A.L., K.R. Brain, and C.J. Allender,“Molecular imprinted polymer sensors: Implications for therapeutics”, Advanced Drug Delivery Reviews, Vol.57, pp. 1875-1889, 2005
7. Hwang, C.C. and W.C. Lee,“Chromatographic characteristics of cholesterol-imprinted polymers prepared by covalent and non-covalent imprinting methods”, Journal of Chromatography A, Vol.962, pp. 69-78, 2002
8. Becker, J.J. and M.R. Gagne,“Exploiting the synergy between coordination chemistry and molecular imprinting in the quest for new catalysts”, Accounts of Chemical Research, Vol.37, pp. 798-804, 2004
9. Visnjevski, A., et al.,“Catalysis of a Diels-Alder cycloaddition with differently fabricated molecularly imprinted polymers”, Catalysis Communications, Vol.6, pp. 601-606, 2005
10. Wulff, G.,“MOLECULAR IMPRINTING IN CROSS-LINKED MATERIALS WITH THE AID OF MOLECULAR TEMPLATES - A WAY TOWARDS ARTIFICIAL ANTIBODIES”, Angewandte Chemie-International Edition in English, Vol.34, pp. 1812-1832, 1995
11. Mosbach, K.,“MOLECULAR IMPRINTING”, Trends in Biochemical Sciences, Vol.19, pp. 9-14, 1994
12. Corriu, R.J.P. and D. Leclercq,“Recent developments of molecular chemistry for sol-gel processes”, Angewandte Chemie-International Edition in English, Vol.35, pp. 1420-1436, 1996
13. Shea, K.J. and D.A. Loy,“Bridged polysilsesquioxanes. Molecular-engineered hybrid organic-inorganic materials”, Chemistry of Materials, Vol.13, pp. 3306-3319, 2001
14. Buckley, A.M. and M. Greenblatt,“THE SOL-GEL PREPARATION OF SILICA-GELS”, Journal of Chemical Education, Vol.71, pp. 599-602, 1994
15. Hench, L.L. and J.K. West,“THE SOL-GEL PROCESS”, Chemical Reviews, Vol.90, pp. 33-72, 1990
16. Jitianu, A., et al.,“Comparative study of the sol-gel processes starting with different substituted Si-alkoxides”, Journal of Non-Crystalline Solids, Vol.319, pp. 263-279, 2003
17. Liu, R.L., et al.,“Comparative study on the hydrolysis kinetics of substituted ethoxysilanes by liquid-state Si-29 NMR”, Journal of Non-Crystalline Solids, Vol.343, pp. 61-70, 2004
18. Xu, Y., et al.,“Ammonia-catalyzed hydrolysis kinetics of mixture of tetraethoxysilane with methyltriethoxysilane by Si-29 NMR”, Journal of Non-Crystalline Solids, Vol.351, pp. 2403-2413, 2005
19. Zheng, N., et al.,“Chromatographic characterization of sulfonamide imprinted polymers”, Microchemical Journal, Vol.69, pp. 153-158, 2001
20. Zheng, N., et al.,“Sulfonamide imprinted polymers using co-functional monomers”, Analytica Chimica Acta, Vol.452, pp. 277-283, 2002
21. Zheng, N., Y.Z. Li, and M.J. Wen,“Sulfamethoxazole-imprinted polymer for selective determination of sulfamethoxazole in tablets”, Journal of Chromatography A, Vol.1033, pp. 179-182, 2004
22. Chen, Z.Y., et al.,“Preparation and evaluation of uniform-sized molecularly imprinted polymer beads used for the separation of sulfamethazine”, Biomedical Chromatography, Vol.19, pp. 533-538, 2005
23. Haginaka, J. and H. Sanbe,“Uniformly sized molecularly imprinted polymer for (S)-naproxen - Retention and molecular recognition properties in aqueous mobile phase”, Journal of Chromatography A, Vol.913, pp. 141-146, 2001
24. de Prada, A.G.V., et al.,“Solid-phase molecularly imprinted on-line preconcentration and voltammetric determination of sulfamethazine in milk”, Analytica Chimica Acta, Vol.539, pp. 125-132, 2005
25. Liu, X.J., et al.,“Monolithic molecularly imprinted polymer for sulfamethoxazole and molecular recognition properties in aqueous mobile phase”, Analytica Chimica Acta, Vol.571, pp. 235-241, 2006
26. Matsui, J., et al.,“MOLECULAR RECOGNITION IN CONTINUOUS POLYMER RODS PREPARED BY A MOLECULAR IMPRINTING TECHNIQUE”, Analytical Chemistry, Vol.65, pp. 2223-2224, 1993
27. Huang, X.D., et al.,“Molecularly imprinted monolithic stationary phases for liquid chromatographic separation of enantiomers and diastereomers”, Journal of Chromatography A, Vol.984, pp. 273-282, 2003
28. Huang, X.D., et al.,“Short columns with molecularly imprinted monolithic stationary phases for rapid separation of diastereomers and enantiomers”, Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, Vol.804, pp. 13-18, 2004
29. Yin, J.F., G.L. Yang, and Y. Chen,“Rapid and efficient chiral separation of nateglinide and its L-enantiomer on monolithic molecularly imprinted polymers”, Journal of Chromatography A, Vol.1090, pp. 68-75, 2005
30. Schweitz, L., L.I. Andersson, and S. Nilsson,“Capillary electrochromatography with predetermined selectivity obtained through molecular imprinting”, Analytical Chemistry, Vol.69, pp. 1179-1183, 1997
31. Schweitz, L., L.I. Andersson, and S. Nilsson,“Rapid electrochromatographic enantiomer separations on short molecularly imprinted polymer monoliths”, Analytica Chimica Acta, Vol.435, pp. 43-47, 2001
32. Schaal, W., et al.,“Synthesis and comparative molecular field analysis (CoMFA) of symmetric and nonsymmetric cyclic sulfamide HIV-1 protease inhibitors”, Journal of Medicinal Chemistry, Vol.44, pp. 155-169, 2001
33. Agarwal, V.K.,“HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHODS FOR THE DETERMINATION OF SULFONAMIDES IN TISSUE, MILK AND EGGS”, Journal of Chromatography, Vol.624, pp. 411-423, 1992
34. Littlefield, N.A., et al.,“CHRONIC TOXICITY CARCINOGENICITY STUDIES OF SULFAMETHAZINE IN FISCHER 344/N RATS - 2-GENERATION EXPOSURE”, Food and Chemical Toxicology, Vol.28, pp. 157-167, 1990
35. Stoev, G. and A. Michailova,“Quantitative determination of sulfonamide residues in foods of animal origin by high-performance liquid chromatography with fluorescence detection”, Journal of Chromatography A, Vol.871, pp. 37-42, 2000
36. Kao, Y.M., et al.,“Multiresidue determination of veterinary drugs in chicken and swine muscles by high performance liquid chromatography”, Journal of Food and Drug Analysis, Vol.9, pp. 84-95, 2001
37. Kishida, K. and N. Furusawa,“Matrix solid-phase dispersion extraction and high-performance liquid chromatographic determination of residual sulfonamides in chicken”, Journal of Chromatography A, Vol.937, pp. 49-55, 2001
38. Furusawa, N.,“Rapid high-performance liquid chromatographic determining technique of sulfamonomethoxine, sulfadimethoxine, and sulfaquinoxaline in eggs without use of organic solvents”, Analytica Chimica Acta, Vol.481, pp. 255-259, 2003
39. Siouffi, A.M.,“Silica gel-based monoliths prepared by the sol-gel method: facts and figures”, Journal of Chromatography A, Vol.1000, pp. 801-818, 2003
40. Brunauer, S., et al.,“On a Theory of the van der Waals Adsorption of Gases”, Journal of the American Chemical Society Vol.62, pp. 1723-1732, 1940
41. Gregg, S.J. and K.S.W. Sing,“Adsorption, surface area and porosity”, Academic Press Inc. ( London), Vol.9, pp. 41-72, 1982
42. Renew, J.E. and C.H. Huang,“Simultaneous determination of fluoroquinolone, sulfonamide, and trimethoprim antibiotics in wastewater using tandem solid phase extraction and liquid chromatography-electrospray mass spectrometry”, Journal of Chromatography A, Vol.1042, pp. 113-121, 2004
43. Lin, C.E., C.C. Chang, and W.C. Lin,“Migration behavior and separation of sulfonamides in capillary zone electrophoresis .3. Citrate buffer as a background electrolyte”, Journal of Chromatography A, Vol.768, pp. 105-112, 1997
44. Zhang, Z., et al.,“PREPARATION OF TRANSPARENT METHYL-MODIFIED SILICA-GEL”, Journal of Non-Crystalline Solids, Vol.189, pp. 212-217, 1995
45. Arrhenius, S.,“The Viscosity of Aqueous Mixture”, Physical and Chemistry, Vol.1, pp. 285-298, 1887