近幾年來，許多研究將胜肽設計為人工水解酶，並期望能模擬天然水解酶的活 性及選擇性，然而設計出高活性水解酶的仍然是一大挑戰。在本研究中，我們利用 催化二聯體以及自組裝的概念來設計一系列人工水解酶，同時也合成聚脯胺酸衍生 物，試圖研究胜肽結構與催化效率間的關聯。我們以 CD 光譜鑑定所設計胜肽的 結構以及穩定性，並利用 UV-Vis 光譜以及酯類受質研究人工水解酶的催化能力。 在第一部分實驗中，利用簡單的聚脯胺酸短胜肽作為人工水解酶，我們發現 PPII 結構的完整性對於人工水解酶的催化效率有很重要的影響，並且催化二聯體內官能 基的間距也是影響催化效率的重要因素。在第二部分的實驗中，以自組裝胜肽作為 人工水解酶，我們發現催化效率有顯著提升，並且催化效率與 β-sheet 結構的穩定 度以及受質結合環境相關，另外我們也發現，自組裝胜肽的碳氮端置換會對酵素的 轉換率(turnover rate)造成很大的改變。在第三部分的實驗中，我們以自組裝胜肽對 甲基對氧磷水解反應進行催化，以探討磷酯水解的催化，實驗結果說明由於自組裝 胜肽所營造的受質結合環境不適用於甲基對氧磷，因此自組裝胜肽並不能有效的進 行催化。本研究說明在人工水解酶中，維持穩定的二級結構以形成有效的催化中心 才能使人工水解酶作為有效的催化劑，並且在本研究中人工水解酶的催化效率有不 俗的表現，對於未來在催化較具挑戰性的酯類水解反應有很大的進展。

Recently, a number of peptide-based enzymes have been designed to mimic the activity and selectivity of natural hydrolysis. But, creating catalysts with great catalytic activity is still challenging. In this study, we designed a series of peptide as artificial enzymes and utilize the concept of catalytic dyad and assembly strategy. We also synthesized proline derivatives in an attempt to study the relationship between the structure and catalytic efficiency of peptides. The secondary structures of peptides were characterized by circular dichroism spectroscopy, and their catalytic efficiency were evaluated by UV-Vis spectroscopy using p-nitrophenyl ester assay. In the first part, the results indicate the higher catalytic efficiency could be attributed to well-defined polyproline II (PPII) structure. In addition, the distance between catalytic dyad is also important for catalytic efficiency. In the second part, the results demonstrate the assembled structure could enhance the catalytic activity on ester hydrolysis significantly. According to the kinetic parameters, the catalytic efficiency lies in the extent of β-sheet structure, as well as a suitable binding pocket for substrates. Furthermore, reversing the sequence within a peptide may dramatically affect the turnover rate of catalyst. In the third part, we carried out the experiments of phosphoester hydrolysis, and self-assembling peptides were used as catalysts for methyl-paraoxon hydrolysis. We find out that self- assembling peptides are incapable of catalyzing methyl-paraoxon hydrolysis effectively, because its binding pocket may not apply to methyl-paraoxon. Our investigation has revealed the necessity of maintaining a stable secondary structure for effective peptide- base enzymes, and promising catalytic efficiency of assembling peptides makes inroads in designing artificial enzymes for challenging substrates.

中文摘要 I
Abstract II
誌謝辭 III
目錄 IV
圖目錄 VII
表目錄 X
第一章 緒論 1
1-1 聚脯胺酸 (Polyproline) 1
1-2 PPII (polyproline II) 結構 2
1-3 立體電子效應 (stereoelectronic effect) 3
1-4 β-sheet 結構 5
1-5 酯類水解反應 (Ester hydrolysis reaction) 6
1-6 天然水解酶作用機制 8
1-7 人工水解酶的設計 10
1-8 研究動機 14
第二章 實驗部分 15
2-1 實驗儀器 15
2-2 實驗藥品 16
2-3 脯胺酸衍生物合成 19
2-3-1 合成步驟 19
2-3-2 合成方法 21
2-4 圓二色光譜儀 (Circular dichroism spectrometer, CD) 26
2-5 固相胜肽合成法 (Solid phase peptide synthesis, SPPS) 30
2-5-1 酯化 (esterification)、醯胺化反應 (amidation) 31
2-5-2 去保護(deprotection) 32
2-5-3 活化(activation) 32
2-5-4 耦合(coupling) 33
2-5-5 切除(cleavage) 33
2-6 胜肽的合成、純化與鑑定 34
2-7 光譜測量 36
2-7-1 UV 光譜測量胜肽濃度 36
2-7-2 CD 光譜測量( Far-UV 光譜) 36
2-7-3 ATR-FTIR 光譜測量 36
2-7-4 催化水解活性實驗 37
2-8 催化活性實驗數據處理 40
2-9 電子顯微鏡 42
2-9-1 穿透式電子顯微鏡(transmission electron microscopy, TEM) 42
2-9-2 原子力顯微鏡(atomic force microscope, AFM) 42
2-10 計算模擬聚脯胺酸結構之研究方法 42
第三章 結果與討論 43
第一部分 聚脯胺酸短胜肽作為人工水解酶 43
3-1 聚脯胺酸短胜肽及其替換骨架衍生物設計 43
3-2 胜肽結構之鑑定 44
3-3 PPII 結構穩定性對酯類水解催化效率探討 46
3-4 計算模擬聚脯胺酸結構 47
第二部分 自組裝胜肽與聚脯胺酸結合作為人工水解酶 50
3-5 含聚脯胺酸片段的自組裝人工水解酶設計 50
3-6 自主裝胜肽二級結構之鑑定 52
3-7 胜肽自組裝結構之鑑定 56
3-7-1 穿透式電子顯微鏡(TEM) 56
3-7-2 原子力顯微鏡(AFM) 60
3-7-3 霍式轉換紅外光譜(FTIR) 64
3-8 自組裝胜肽對酯類水解催化效率探討 65
3-8-1 不同 pH 值下自組裝結構對酯類水解催化效率探討 65
3-8-2 自組裝胜肽內聚脯胺酸片段對酯類水解催化效率探討 70
3-8-3 自組裝胜肽碳氮端置換對酯類水解催化影響探討 72
3-8-4 自組裝胜肽與相關研究的酯類水解催化效率比較 74
第三部分 自組裝人工水解酶對磷酯水解催化探討 76
第四章 結論與展望 79
參考文獻 81
附錄 87

1. Traub, W. S., U. Structure of poly-L-proline I. nature. Nature 1963, 198, 1165-1166.
2. Cowan, P. M.; McGavin, S. Structure of poly-L-proline. Nature 1955, 176, 501-503.
3. Kakinoki, S.; Hirano, Y.; Oka, M. On the stability of polyproline-I and II structures of proline oligopeptides. Polym. Bull. 2005, 53, 109-115.
4. Shi, Z.; Chen, K.; Liu, Z.; Kallenbach, N. R. Conformation of the backbone in unfolded proteins. Chem. Rev. 2006, 106, 1877-1897.
5. Liu, Z.; Chen, K.; Ng, A.; Shi, Z.; Woody, R. W.; Kallenbach, N. R. Solvent dependence of PII conformation in model alanine peptides. J. Am. Chem. Soc. 2004, 126, 15141-15150.
6. Hinderaker, M. P.; Raines, R. T. An electronic on protein structure. Protein Sci. 2003, 12, 1188-1194.
7. Choudhary, A.; Gandla, D.; Krow, G. R.; Raines, R. T. Nature of amide carbonyl--carbonyl interactions in proteins. J. Am. Chem. Soc. 2009, 131, 7244-7246.
8. Adzhubei, A. A.; Sternberg, M. J. Left-handed polyproline II helices commonly occur in globular proteins. J. Mol. Biol. 1993, 229, 472-493.
9. Stapley, B. J.; Creamer, T. P. A survey of left-handed polyproline II helices. Protein Sci. 1999, 8, 587-595.
10. Choudhary, A.; Pua, K. H.; Raines, R. T. Quantum mechanical origin of the conformational preferences of 4-thiaproline and its S-oxides. Amino Acids 2011, 41, 181-186.
11. Wolfe, S. Gauche effect. Stereochemical consequences of adjacent electron pairs and polar bonds. Acc. Chem. Res. 1972, 5, 102-111.
12. DeRider, M. L.; Wilkens, S. J.; Waddell, M. J.; Bretscher, L. E.; Weinhold, F.; Raines, R. T.; Markley, J. L. Collagen stability: insights from NMR spectroscopic and hybrid density functional computational investigations of the effect of electronegative substituents on prolyl ring conformations. J. Am. Chem. Soc. 2002, 124, 2497-2505.
13. Taylor, C. M.; Hardré, R.; Edwards, P. J. B. The Impact of pyrrolidine hydroxylation on the conformation of proline-containing peptides. J. Org. Chem. 2005, 70, 1306-1315.
14. Bretscher, L. E.; Jenkins, C. L.; Taylor, K. M.; DeRider, M. L.; Raines, R. T. Conformational stability of collagen relies on a stereoelectronic effect. J. Am. Chem. Soc. 2001, 123, 777-778.
15. Lelson, D. L., Cox, M. M., Principles of biochemistry (4th ed.). W. H. Freeman and coompany: New York, 2005.
16. Sarkhel, B.; Chatterjee, A.; Das, D. Covalent catalysis by cross β amyloid nanotubes. J. Am. Chem. Soc. 2020, 142, 4098-4103.
17. Sarroukh, R.; Goormaghtigh, E.; Ruysschaert, J. M.; Raussens, V. ATR-FTIR: a "rejuvenated" tool to investigate amyloid proteins. Biochim. Biophys. Acta 2013, 1828, 2328-2338.
18. Bruice, T. C. S., G. L. Imidazole catalysis. I. The catalysis of the hydrolysis of phenyl acetates by imidazole. J. Am. Chem. Soc. 1957, 79, 1663-1667.
19. Kirsch, J. F.; Jencks, W. P. Base catalysis of imidazole catalysis of ester hydrolysis. J. Am. Chem. Soc. 1964, 86, 833-837.
20. Bezer, S.; Matsumoto, M.; Lodewyk, M. W.; Lee, S. J.; Tantillo, D. J.; Gagné, M. R.; Waters, M. L. Identification and optimization of short helical peptides with novel reactive functionality as catalysts for acyl transfer by reactive tagging. Org. Biomol. Chem. 2014, 12, 1488-1494.
21. Head, M. B.; Mistry, K. S.; Ridings, B. J.; Smith, C. A.; Parker, M. J. Nucleophilic and enzymic catalysis of p-Nitrophenylacetate hydrolysis. J. Chem. Educ. 1995, 72, 184.
22. Ohkubo, K.; Ogata, H.; Yamaki, K. Stereoselective esterolysis of dipeptide-type amino acid esters with Di- and Tri-peptide-type L-histidine derivatives in the solution of a chiral cationic surfactant. J. Mol. Catal. 1984, 26, 1-5.
23. Barton, J. S. A Comprehensive enzyme kinetic exercise for biochemistry. J. Chem. Educ. 2011, 88, 1336-1339.
24. Hiscock, J. R.; Sambrook, M. R.; Cranwell, P. B.; Watts, P.; Vincent, J. C.; Xuereb, D. J.; Wells, N. J.; Raja, R.; Gale, P. A. Tripodal molecules for the promotion of phosphoester hydrolysis. Chem. Commun. 2014, 50, 6217-6220.
25. Lengyel, Z.; Rufo, C. M.; Moroz, Y. S.; Makhlynets, O. V.; Korendovych, I. V. Copper-containing catalytic amyloids promote phosphoester hydrolysis and tandem reactions. ACS Catalysis 2018, 8, 59-62.
26. Li, Y.; Zhao, Y.; Hatfield, S.; Wan, R.; Zhu, Q.; Li, X.; McMills, M.; Ma, Y.; Li, J.; Brown, K. L.; He, C.; Liu, F.; Chen, X. Dipeptide seryl-histidine and related oligopeptides cleave DNA, protein, and a carboxyl ester. Biorg. Med. Chem. 2000, 8, 2675-2680.
27. Khersonsky, O.; Tawfik, D. S. The histidine 115-histidine 134 dyad mediates the lactonase activity of mammalian serum paraoxonases. J. Biol. Chem. 2006, 281, 7649-7656.
28. Quirk, D. J.; Raines, R. T. His ... Asp catalytic dyad of ribonuclease A: histidine pKa values in the wild-type, D121N, and D121A enzymes. Biophys. J. 1999, 76, 1571-1579.
29. Simón, L.; Goodman, J. M. Enzyme catalysis by hydrogen bonds: The balance between transition state binding and substrate binding in oxyanion holes. J. Org. Chem. 2010, 75, 1831-1840.
30. Kamerlin, S. C. L.; Chu, Z. T.; Warshel, A. On catalytic preorganization in oxyanion holes: Highlighting the problems with the gas-phase modeling of oxyanion holes and illustrating the need for complete enzyme models. J. Org. Chem. 2010, 75, 6391-6401.
31. Steitz, T. A.; Henderson, R.; Blow, D. M. Structure of crystalline alpha-chymotrypsin. 3. Crystallographic studies of substrates and inhibitors bound to the active site of alpha-chymotrypsin. J. Mol. Biol. 1969, 46, 337-348.
32. Vriezema, D. M.; Comellas Aragonès, M.; Elemans, J. A.; Cornelissen, J. J.; Rowan, A. E.; Nolte, R. J. Self-assembled nanoreactors. Chem. Rev. 2005, 105, 1445-1489.
33. Roy, S.; Pericàs, M. A. Functionalized nanoparticles as catalysts for enantioselective processes. Org. Biomol. Chem. 2009, 7, 2669-2677.
34. Duncan, K. L.; Ulijn, R. V. Short peptides in minimalistic biocatalyst design. Biocatalysis 2015, 67.
35. Matsumoto, M.; Lee, S. J.; Gagné, M. R.; Waters, M. L. Cross-strand histidine–aromatic interactions enhance acyl-transfer rates in beta-hairpin peptide catalysts. Org. Biomol. Chem. 2014, 12, 8711-8718.
36. Matsumoto, M.; Lee, S. J.; Waters, M. L.; Gagné, M. R. A Catalyst selection protocol that identifies biomimetic motifs from β-hairpin libraries. J. Am. Chem. Soc. 2014, 136, 15817-15820.
37. Burton, A. J.; Thomson, A. R.; Dawson, W. M.; Brady, R. L.; Woolfson, D. N. Installing hydrolytic activity into a completely de novo protein framework. Nat. Chem. 2016, 8, 837-844.
38. Zastrow, M. L.; Pecoraro, V. L. Influence of active site location on catalytic activity in de novo-designed zinc metalloenzymes. J. Am. Chem. Soc. 2013, 135, 5895-5903.
39. Zastrow, M. L.; Peacock, A. F.; Stuckey, J. A.; Pecoraro, V. L. Hydrolytic catalysis and structural stabilization in a designed metalloprotein. Nat. Chem. 2011, 4, 118-123.
40. Wang, P. S. P.; Nguyen, J. B.; Schepartz, A. Design and high-resolution structure of a β3-peptide bundle catalyst. J. Am. Chem. Soc. 2014, 136, 6810-6813.
41. Zhang, Q.; He, X.; Han, A.; Tu, Q.; Fang, G.; Liu, J.; Wang, S.; Li, H. Artificial hydrolase based on carbon nanotubes conjugated with peptides. Nanoscale 2016, 8, 16851-16856.
42. Zaramella, D.; Scrimin, P.; Prins, L. J. Self-assembly of a catalytic multivalent peptide–nanoparticle complex. J. Am. Chem. Soc. 2012, 134, 8396-8399.
43. Poznik, M.; König, B. Cooperative hydrolysis of aryl esters on functionalized membrane surfaces and in micellar solutions. Org. Biomol. Chem. 2014, 12, 3175-3180.
44. Rufo, C. M.; Moroz, Y. S.; Moroz, O. V.; Stöhr, J.; Smith, T. A.; Hu, X.; DeGrado, W. F.; Korendovych, I. V. Short peptides self-assemble to produce catalytic amyloids. Nat. Chem. 2014, 6, 303-309.
45. Fasting, C.; Schalley, C. A.; Weber, M.; Seitz, O.; Hecht, S.; Koksch, B.; Dernedde, J.; Graf, C.; Knapp, E. W.; Haag, R. Multivalency as a chemical organization and action principle. Angew. Chem. Int. Ed. 2012, 51, 10472-10498.
46. Huang, Z.; Guan, S.; Wang, Y.; Shi, G.; Cao, L.; Gao, Y.; Dong, Z.; Xu, J.; Luo, Q.; Liu, J. Self-assembly of amphiphilic peptides into bio-functionalized nanotubes: a novel hydrolase model. J. Mater. Chem. B 2013, 1, 2297-2304.
47. Hung, P.-Y.; Chen, Y.-H.; Huang, K.-Y.; Yu, C.-C.; Horng, J.-C. Design of polyproline-based catalysts for ester hydrolysis. ACS Omega 2017, 2, 5574-5581.
48. Ting, Y.-H.; Chen, H.-J.; Cheng, W.-J.; Horng, J.-C. Zinc(II)–histidine induced collagen peptide assemblies: Morphology modulation and hydrolytic catalysis evaluation. Biomacromolecules 2018, 19, 2629-2637.
49. Huang, K.-Y.; Yu, C.-C.; Horng, J.-C. Conjugating catalytic polyproline fragments with a self-assembling peptide produces efficient artificial hydrolases. Biomacromolecules 2020, 21, 1195-1201.
50. Purdie, N. Circular dichroism and the conformational analysis of biomolecules edited by Gerald D. Fasman (Brandeis University). Plenum Press:  New York. 1996. Journal of the American Chemical Society 1996, 118, 12871-12871.
51. Merrifield, R. B. Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J. Am. Chem. Soc. 1963, 85, 2149-2154.
52. Michaelis, L. M. Die kinetik der invertinwirkung. Biochem. Z. 1913, 49, 333–369.
53. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams; Ding, F.; Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J. Gaussian 16 Rev. C.01, Wallingford, CT, 2016.
54. Schneider, J. P.; Pochan, D. J.; Ozbas, B.; Rajagopal, K.; Pakstis, L.; Kretsinger, J. Responsive hydrogels from the intramolecular folding and self-assembly of a designed peptide. J. Am. Chem. Soc. 2002, 124, 15030-15037.
55. Zhong, H.; Carlson, H. A. Conformational studies of polyprolines. J. Chem. Theory. Comput. 2006, 2, 342-353.
56. Zhang, C.; Shafi, R.; Lampel, A.; MacPherson, D.; Pappas, C. G.; Narang, V.; Wang, T.; Maldarelli, C.; Ulijn, R. V. Switchable hydrolase based on reversible formation of supramolecular catalytic site using a self-assembling peptide. Angew. Chem. Int. Ed. Engl. 2017, 56, 14511-14515.
57. Paetzel, M.; Dalbey, R. E. Catalytic hydroxyl/amine dyads within serine proteases. Trends Biochem. Sci 1997, 22, 28-31.
58. Moriarty, D. F.; Raleigh, D. P. Effects of sequential proline substitutions on amyloid formation by human amylin20-29. Biochemistry 1999, 38, 1811-1818.
59. Soto, C.; Sigurdsson, E. M.; Morelli, L.; Asok Kumar, R.; Castaño, E. M.; Frangione, B. β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Implications for Alzheimer's therapy. Nat. Med. 1998, 4, 822-826.
60. Abedini, A.; Meng, F.; Raleigh, D. P. A Single-point mutation converts the highly amyloidogenic human islet amyloid polypeptide into a potent fibrillization inhibitor. J. Am. Chem. Soc. 2007, 129, 11300-11301.
61. Kanchi, P. K.; Dasmahapatra, A. K. Polyproline chains destabilize the Alzheimer’s amyloid-β protofibrils: A molecular dynamics simulation study. J. Mol. Graphics Modell. 2019, 93, 107456.
62. Nagy-Smith, K.; Moore, E.; Schneider, J.; Tycko, R. Molecular structure of monomorphic peptide fibrils within a kinetically trapped hydrogel network. Proc. Natl. Acad. Sci. U. S. A. 2015, 112, 9816-9821.
63. Singh, N.; Conte, M. P.; Ulijn, R. V.; Miravet, J. F.; Escuder, B. Insight into the esterase like activity demonstrated by an imidazole appended self-assembling hydrogelator. Chem. Commun. 2015, 51, 13213-13216.
64. Friedmann, M. P.; Torbeev, V.; Zelenay, V.; Sobol, A.; Greenwald, J.; Riek, R. Towards prebiotic catalytic amyloids using high throughput screening. PLOS ONE 2015, 10, e0143948.
65. Bolon, D. N.; Mayo, S. L. Enzyme-like proteins by computational design. Proc. Natl. Acad. Sci. U. S. A. 2001, 98, 14274-14279.
66. Der, B. S.; Edwards, D. R.; Kuhlman, B. Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering. Biochemistry 2012, 51, 3933-3940.
67. Studer, S.; Hansen, D. A.; Pianowski, Z. L.; Mittl, P. R. E.; Debon, A.; Guffy, S. L.; Der, B. S.; Kuhlman, B.; Hilvert, D. Evolution of a highly active and enantiospecific metalloenzyme from short peptides. Science 2018, 362, 1285-1288.
68. Moroz, Y. S.; Dunston, T. T.; Makhlynets, O. V.; Moroz, O. V.; Wu, Y.; Yoon, J. H.; Olsen, A. B.; McLaughlin, J. M.; Mack, K. L.; Gosavi, P. M.; van Nuland, N. A. J.; Korendovych, I. V. New tricks for old proteins: Single mutations in a nonenzymatic protein give rise to various enzymatic activities. J. Am. Chem. Soc. 2015, 137, 14905-14911.
69. Broo, K. S.; Brive, L.; Ahlberg, P.; Baltzer, L. Catalysis of hydrolysis and transesterification reactions of p-Nitrophenyl esters by a designed helix−loop−helix dimer. J. Am. Chem. Soc. 1997, 119, 11362-11372.
70. Luong, T. Q.; Erwin, N.; Neumann, M.; Schmidt, A.; Loos, C.; Schmidt, V.; Fändrich, M.; Winter, R. hydrostatic pressure increases the catalytic activity of amyloid fibril enzymes. Angew. Chem. Int. Ed. 2016, 55, 12412-12416.
71. Verpoorte, J. A.; Mehta, S.; Edsall, J. T. Esterase activities of human carbonic anhydrases B and C. J. Biol. Chem. 1967, 242, 4221-4229.
72. Wilson, C.; Cooper, N. J.; Briggs, M. E.; Cooper, A. I.; Adams, D. J. Investigating the breakdown of the nerve agent simulant methyl paraoxon and chemical warfare agents GB and VX using nitrogen containing bases. Org. Biomol. Chem. 2018, 16, 9285-9291.
73. Casida, J. E.; Quistad, G. B. Organophosphate toxicology: safety aspects of nonacetylcholinesterase secondary targets. Chem. Res. Toxicol. 2004, 17, 983-998.
74. Liu, Y.; Moon, S.-Y.; Hupp, J. T.; Farha, O. K. Dual-function metal–organic framework as a versatile catalyst for detoxifying chemical warfare agent simulants. ACS Nano 2015, 9, 12358-12364.