Caging Molecules: Catch Me If You Can!

Transcription

1 Caging Molecules: Catch Me If You Can! Xiaoyong Li Department of Chemistry Michigan State University ov. 2nd, 2005 Aida, T. et.al. Angew. Chem. Int. Ed. 2001, 40, 1857.

2 Three Questions To Be Answered What?are caging molecules? How?to cage molecules? Why? to cage molecules?

3 K + What are Caging Molecules? K + H 18-Crown-6-K + H H H H H H HH Guest H H H H H H H H H n CD α β γ n Cyclodextrin Rocuronium bromide euromuscular blocker Born, A.; Bradley, M.; Cameron, K.; Clark, J. K.; Egmond, J. van; Feilden, H.; Maclean, E. J.; Muir, A. W.; Palin, R.; Rees, D.C.; Zhang, M.-Q. Agnew. Chem., Int. Ed. 2002, 41, 265. H H - Br Ac +

4 K + What are Caging Molecules? H 18-Crown-6-K + H H H H H HH Guest H H H H H H H H H n CD α β γ n Cyclodextrin H Z = C 2 Me ~83% Fullenrene Iwamatsu, S.; Murata, S.; Andoh, Y.; Minoura, M.; Kobayashi, K.; Mizorogi,.; agase, S. J. rg. Chem. 2005, 70, 4820.

5 What are Caging Molecules? Host-guest chemistry CH H 3 C CH 3 3 CH H 3 H H H Host S S Guest S S H CH3 H H H CH CH 3 3 C 3 H Cacerand Encapsulation / imprisonment Cram, D. J.; Karbach, S.; Kim, Y. H.; Aczynskyj, L.; Kalleymeyn, G. W. J. Am. Chem. Soc. 1985, 107, 2575.

6 How to Cage Molecules Building a host cage Synthesis by covalent bonding Self-assembly by noncovalent interactions Caging guest molecules van der Waals force Donor-acceptor interaction π - π stacking / CH - π interaction Electrostatic attraction

7 Why to Cage Molecules? Molecular storage - stabilize reactive species / dyes / drugs - selective extraction Acquire insights for enzymatic process - conduct chemical transformations in cages

8 Molecular storage Stabilize reactive species / dyes / drugs EtH + Et CEt rhodamine 6G Ultrastable Extended fluorescence life Unchanged fluorescent activity K a > M -1 Cucurbit[7]uril au, W. M.; Mohanty J. Angew. Chem. Int. Ed. 2005, 44, 3750.

9 Why to Cage Molecules? Molecular storage - stabilize reactive species / dyes / drugs - selective extraction

10 Molecular Extraction of Fullerenes - Aida s Story Carbon nanotube Superconductor HIV protease inhibitor C 60 Fullerenes C 60 (98%) C 60 / C 70 (9:1) C 70 (98%) C 84 (98%) Unite 1g 500mg 50mg 5mg Price $ 246 $ 141 $ 153 $ 697 Aldrich Catalog , 937

11 Caging Fullerenes by Dimeric Dimeric Metalloporphyrin Metalloporphyrins Host Hex Hex Hex Hex (CH 2 ) 6 (CH2 ) 6 Hex Hex Hex Hex Guest C 60 Bpy K a =6.7X10 5 M -1 << 3.2X10 8 M -1 C 60 Host Host-C 60 Tashiro, K.; Aida, T.; Zheng, J.-Y.; Kinbara, K.; Saigo, K.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc. 1999, 121, 9477.

12 Caging C 60 by Dimeric Metalloporphyrins C 60 Free host -C23=2.918 Å -C24=2.765 Å UV titration of host with C 60 in benzene Proof from MR C 60 as acceptor Zheng, J.-Y.;Tashiro, K.; Hirabayashi, Y.; Kinbara, K.; Saigo, K.; Aida, T.; Sakamoto,S.; Yamaguchi, K.; Aida, T. Angew. Chem. Int. Ed. 2001, 40, 1857.

13 Caging Different Fullerenes Hex Hex Hex Hex (CH 2 ) 6 (CH2 ) 6 Hex Hex Hex Hex Log K association C 60 C 70 C 96 Guest C 12 H 25 C 12 H 25 (CH 2 ) 6 (CH 2 ) 6 C 12 H 25 C 12 H 25 Shoji, Y.; Tashiro, K.; Aida, T. J. Am. Chem. Soc. 2004, 126, 6570.

14 Selective Extraction of Higher Fullerenes C 12 H 25 C 12 H 25 Mixture of fullerenes host (CH 2 ) 6 (CH 2 ) 6 C 12 H 25 C 12 H 25 Host-C >70 Enriched C 96 host Host-C >100 Enriched C 102 ~C 110 Shoji, Y.; Tashiro, K.; Aida, T. J. Am. Chem. Soc. 2004, 126, 6570.

15 Selective Extraction of Higher Fullerenes 20% C 70 in C 60 Et Et Et Et Et Et Et Et (CH 2 ) 6 (CH2 ) 6 Et Et Et Et Et Et Et Et 91% C 70 in C 60 Porphyrincolumn Zheng, J.-Y.;Tashiro, K.; Hirabayashi, Y.; Kinbara, K.; Saigo, K.; Aida, T.; Sakamoto,S.; Yamaguchi, K.; Aida, T. Angew. Chem. Int. Ed. 2001, 40, 1857.

16 Why to Cage Molecules? Molecular storage - stabilize reactive species / dyes / drugs - selective extraction Acquire insights for enzymatic process - conduct chemical transformations in cages

17 A Comparison between atural Enzyme & Supermolecular Cage atural enzyme: selective substrate binding induced proximity hydrophobic interior complex superstructure hard to make Supermolecular cage: selective caging by size, shape, etc space-restricted environment hydrophobic interior well-defined and tunable structure

18 Approach to Supermolecular Cage Synthesis by covalent bonding Self-assembly by noncovalent interactions

19 Self-assembly Even a common, ordinary brick wants to be something more than it is. --Louis Kahn The Encyclopedia of Twentieth-Century Architecture (Ed.: R.Stephen Sennott), Fitzroy Dearborn, Chicago, 2002.

20 Self-assembly by oncovanlent Interactions - Hydrogen bonding fast equilibration / reversible solvent competition for H-bonding - Metal-ligand coordination greater strength more rigidity stable in aqueous solution

21 H-bonding Based Supermolecular Cage H R R H H H H H H R R H R= 4-n-heptylphenyl Volume = 320 Å 3 Softball Kang, J.; Rebek, J., Jr. ature 1997, 385, 50. Kang, J.; Santamarı a, J.; Hilmersson,G.; Rebek, J., Jr. J. Am. Chem. Soc. 1998, 120, 7389.

22 Functions of Metal-ligand Based Supermolecular Cages Fujita s story - molecular triangles Hupp s story molecular squares

23 Self-Assembly of Molecular Triangle -Fujita s Story n

24 M 6 L 4 Host Assembly-Molecular Paneling Pd Pd 12+ Pd Pd Pd Pd H 2 H 2 Pd 2 2 tube , water soluble Hydrophobic cavity bowl Pd = cage H 2 Pd H 2

25 [2+2] Photodimerization of lefins within anocages 2 hv + syn Poor yield and selectivity in solution phase Improved reactions need to be conducted in crystalline state The cage effect restrictions from lattice anti 2 hv + D 2 syn 2 mm, 0.5h > 98% yield anti Yoshizawa, M.; Takeyama, Y.; Kusukawa, T.; Fujita, M. Angew. Chem. Int. Ed. 2002, 41, 1347.

26 [2+2] Photodimerization of lefins within anocages 2 hv X benzene HT-syn HH-syn HT-anti HH-anti 150mM Yoshizawa, M.; Takeyama, Y.; Kusukawa, T.; Fujita, M. Angew. Chem. Int. Ed. 2002, 41, 1347.

27 [2+2] Photodimerization of lefins within anocages 2 hv D mM, 3h HT-syn HH-syn HT-anti HH-anti CDCl 3 HT-syn > 98% yield Yoshizawa, M.; Takeyama, Y.; Kusukawa, T.; Fujita, M. Angew. Chem. Int. Ed. 2002, 41, 1347.

28 [2+2] Cross-Photodimerization A + B hv A'-B' + A'-A' + B'-B' syn / anti syn / anti syn / anti + caging A+ B A B + A A + B B hv A'-B' + A'-A' + B'-B' syn syn syn

29 [2+2] Cross-Photodimerization of lefins within anocages + 1 : 1 Cage (1eq.) 80 o C, 10min D inert to hv D 2 hv, 3h size compatibility CDCl 3 97% yield Yoshizawa, M. Takeyama,Y.; kano,t.; Fujita M. J. Am. Chem. Soc. 2003, 125, 3243.

30 Photochemical xidation of Alkanes H H hv 2 + CH 3 C Air, Lewis Acid Can we do it in a greener way? Pd = Pd Shul pin, G. B.; izova, G. V.; Kozlov, Y.. ew. J. Chem. 1996, 20, Yoshizawa, M.; Miyagi, S.; Kawano, M.; Ishiguro, K.; Fujita, M. J. Am. Chem. Soc. 2004, 126, 9172.

31 Alkane xidation via Photochemical Excitation of Molecular Cage H H 4 hv H 2, r.t., 30min + 1 : Pd = Pd Yoshizawa, M.; Miyagi, S.; Kawano, M.; Ishiguro, K.; Fujita, M. J. Am. Chem. Soc. 2004, 126, 9172.

32 Alkane xidation via Photochemical Excitation of Molecular Cage H 4 hv H 2, r.t., 30min Ar hv 12+ Ar Substrate? Solvent? Metal? H 2 CH 3 C Solid Pd 2+ Pt 2+ Pd = Pd Anion? Ligand? 3 - PF 6 - Yoshizawa, M.; Miyagi, S.; Kawano, M.; Ishiguro, K.; Fujita, M. J. Am. Chem. Soc. 2004, 126, 9172.

33 Mechanism of Alkane xidation in Photo Reactor hv G G G' H H' H 12+ Generate radical in triazine ligand by hv e transfer from alkane to L generating R. & L Trap R. by H 2 or 2 releasing product Yoshizawa, M.; Miyagi, S.; Kawano, M.; Ishiguro, K.; Fujita, M. J. Am. Chem. Soc. 2004, 126, 9172.

34 Alkane xidation via Photochemical Excitation of Molecular Cage 2.6 Å Close contact is crucial! o oxidation with nanobowl Yoshizawa, M.; Miyagi, S.; Kawano, M.; Ishiguro, K.; Fujita, M. J. Am. Chem. Soc. 2004, 126, 9172.

35 Metal-ligand Based Supermolecular Cages Fujita s story - molecular triangles Hupp s story molecular squares

36 A Paradigm of Artificial Enzyme -Hupp s Story Fe Ⅱ Mn Ⅲ Cl - R 1 R 4 + xidant Catalyst R 1 R 4 R 2 R 3 R 2 R 3 Cytochrome P450 T = 50 t 1/2 = 10 min Merlau, M. L.; Mejia, M. del P.; guyen, S. T.; Hupp, J. T. Angew. Chem. Int. Ed. 2001, 40, 4239.

37 Mechanism for Metalloporphyrin Catalyzed Epoxidation R 1 Mn Ⅲ Cl [] R 2 R 1 R 1 R 2 Mn Ⅴ Mn Ⅴ Mn Ⅲ + Cl Cl Cl R 2 Mn Ⅲ Cl + Mn Ⅴ Mn Ⅳ Mn Ⅳ Cl oxo-dimer 2 Cl - Collman, J. P.; Kodadek, T.; Raybuck, S. A.; Brauman, J. I. J. Am. Chem. Soc. 1985, 107, Collman, J. P.; Brauman, J. I.; Meunier, B.; Hayashi, T.; Kodadek, T.; Raybuck, S. A. J. Am.. Chem. Soc. 1985, 107, 2000.

38 Artificial Enzyme from Directed Selfassembly of Molecular Squares Design a cage 18 Å Cl(C) 3 Re Re(C) 3 Cl 18 Å Mn Ⅲ 14 Å Cl(C) 3 Re Re(C) 3 Cl A perfect cavity! Merlau, M. L.; Mejia, M. del P.; guyen, S. T.; Hupp, J. T. Angew. Chem. Int. Ed. 2001, 40, 4239.

39 Artificial Enzyme from Directed Selfassembly of Molecular Squares 9 Å Cl(C) 3 Re Re(C) 3 Cl Host + Mn Ⅲ K a =10 6 M -1 Mn Ⅲ 18 Å Cl(C) 3 Re Re(C) 3 Cl + PHI Ph Catalyst CH 2 Cl 2, r.t. Ph 92% T = 500 t 1/2 = 3h Merlau, M. L.; Mejia, M. del P.; guyen, S. T.; Hupp, J. T. Angew. Chem. Int. Ed. 2001, 40, 4239.

40 Improve the Catalytic Activity of Artificial Enzyme by Enhance the Caging Cl(C) 3 Re Re(C) 3 Cl Mn Ⅲ Mn Ⅲ T= 65 Cl(C) 3 Re Re(C) 3 Cl Catalyst + PHI Ph CH 2 Cl 2, r.t. Ph 92% K a =10 7 M -1 T=1500 Merlau, M. L.; Mejia, M. del P.; guyen, S. T.; Hupp, J. T. Angew. Chem. Int. Ed. 2001, 40, 4239.

41 Summary Caging molecules has been extensively investigated as an important tool for molecule storage, catalysis and mimicking nature Fabricating supermolecular cages was achieved by many methods especially by self-assembly via noncovalent interactions as H-bonding & metal-ligand coordination Understanding the nature of caging molecules promotes the development of molecular reactors and artificial enzymes It s all about the space --Julius Rebek Jr.

42 Louis Kahn Yale University Art Gallery 1953, ew Haven, Connecticut

43 Louis Kahn Salk Institute for Biologic Studies 1965, La Jolla, California

44 Louis Kahn ational Assembly Building 1963, Dhaka, Bangladesh

45

46 Cl(C) 3 Re Re(C) 3 Cl Mn Ⅲ Cl(C) 3 Re Re(C) 3 Cl

47 Acknowledgement Dr. Borhan Dr. Wagner Chrysoula, Dan, Jennifer, Jun, Marina, Shang, Sing, Stewart, Tao, Xiaofei Yana