Caging Molecules: Catch Me If You Can€¦ · Aida, T. et.al. Angew. Chem. Int. Ed. 2001, 40, 1857. Caging Molecules: Catch Me If You Can ! Xiaoyong Li Department of Chemistry Michigan

Aida, T. et.al. Angew. Chem. Int. Ed. 2001, 40, 1857.

Caging Molecules: Catch Me If You Can !

Xiaoyong LiDepartment of Chemistry Michigan State University

Nov. 2nd, 2005

• Why ?

Three Questions To Be Answered

• What ?are caging molecules ?

to cage molecules ?

• How ?to cage molecules ?

What are Caging Molecules?

CyclodextrinCyclodextrin

K+

18-Crown-6-K+18-Crown-6-K+

K+

O

OHHO

OH

O

OOH

HO OHO

OOH

OH

OH

O

OO

OHOH

HO

OOH

OHHO

O

OOH

HO

HO

O

n

γ

α

β

CD n1

3

2

Guest

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.

Rocuronium bromide

Neuromuscular blocker

N

HHO

NO

Br

OAc

-

+


Iwamatsu, S.; Murata, S.; Andoh, Y.; Minoura, M.; Kobayashi, K.; Mizorogi, N.; Nagase, S. J. Org. Chem. 2005, 70, 4820.

K+

FullenreneFullenrene

CyclodextrinCyclodextrin

O

OHHO

OH

O

OOH

HO OHO

OOH

OH

OH

O

OO

OHOH

HO

OOH

OHHO

O

OOH

HO

HO

O

n

γ

α

β

CD n1

3

2

Guest

18-Crown-6-K+18-Crown-6-K+

~83%Z = CO2Me

• Encapsulation / imprisonment

• Host-guest chemistry


Cram, D. J.; Karbach, S.; Kim, Y. H.; Aczynskyj, L.; Kalleymeyn, G. W. J. Am. Chem. Soc. 1985, 107, 2575.

Host

Cacerand

OO O OO O O O

H3C CH3CH3CH3

H HH H

OO O OO O

O O

CH3CH3CH3 C3H

H HH H

S SSS Guest

Building a host cage

Caging guest molecules

• Synthesis by covalent bonding• Self-assembly by noncovalent interactions

• van der Waals force• Donor-acceptor interaction• π - π stacking / CH - π interaction• Electrostatic attraction

How to Cage Molecules

Why to Cage Molecules?

Molecular storage- stabilize reactive species / dyes / drugs- selective extraction

Acquire insights for enzymatic process- conduct chemical transformations in cages

Molecular storage

Cucurbit[7]urilCucurbit[7]uril

Nau, W. M.; Mohanty J. Angew. Chem. Int. Ed. 2005, 44, 3750.

O NEtEtHN

COOEt

+

rhodamine 6G

Ka> 50000 M-1

Stabilize reactive species / dyes / drugs

• Ultrastable • Extended fluorescence life• Unchanged fluorescent activity



Molecular Extraction of Fullerenes - Aida’s Story

$ 6975mgC84 (98%)$ 15350mgC70 (98%)$ 141500mgC60 / C70 (9:1)$ 2461gC60 (98%)PriceUniteFullerenes

Aldrich Catalog. 2004-2005, 937

C60

Carbon nanotubeSuperconductorHIV protease inhibitor

Caging Fullerenes by Dimeric Metalloporphyrins

Tashiro, K.; Aida, T.; Zheng, J.-Y.; Kinbara, K.; Saigo, K.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc.1999, 121, 9477.

Ka=6.7X105 M-1 << 3.2X108 M-1Ka=6.7X105 M-1 << 3.2X108 M-1

Dimeric MetalloporphyrinDimeric Metalloporphyrin

Bpy

Guest

N

N

C60

NN N

NZn

Hex Hex

Hex Hex

N

N NN

Zn

Hex Hex

Hex Hex

O O

OO

(CH2)6 (CH2)6

Host

C60

Host

Host-C60

UV titration of host with C60 in benzene

Caging C60 by Dimeric Metalloporphyrins

Free host

C60 as acceptorC60 as acceptor

Zn-C23=2.918 Å

Zn-C24=2.765 Å

Zn-C23=2.918 Å

Zn-C24=2.765 Å

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.

C60

Proof from NMRProof from NMR

Caging Different Fullerenes

Shoji, Y.; Tashiro, K.; Aida, T. J. Am. Chem. Soc. 2004, 126, 6570.

5.0

6.0

7.0

8.0

Log

Kas

soci

atio

n

C60 C70 C96

5.7

5.0

7.1

5.9

7.57.1

Guest

NN N

NZn

Hex Hex

Hex Hex

N

N NN

Zn

Hex Hex

Hex Hex

O O

OO

(CH2)6 (CH2)6

N

N NN

Zn

N

N NN

Zn

O O

OO(CH2)6 (CH2)6

OC12H25

OC12H25C12H25O

C12H25O

Selective Extraction of Higher Fullerenes

Shoji, Y.; Tashiro, K.; Aida, T. J. Am. Chem. Soc. 2004, 126, 6570.

N

N NN

Zn

N

N NN

Zn

O O

OO

(CH2)6 (CH2)6

OC12H25

OC12H25C12H25O

C12H25OMixture of fullerenesMixture of fullerenes

Enriched C96Enriched C96

host

NN

Enriched C102~C110Enriched C102~C110

host

NN

Host-C>70

Host-C>100

Selective Extraction of Higher Fullerenes

20% C70 in C6020% C70 in C60

91% C70 in C6091% C70 in C60

NN N

NZn

EtEt Et

Et

EtEt Et

Et

N

N NN

ZnEt

Et EtEt

EtEt Et

Et

O O

OO

(CH2)6 (CH2)6

‘ Porphyrin column ‘‘ Porphyrin column ‘

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.



Acquire insights for enzymatic process- conduct chemical transformations in cages

A Comparison between Natural Enzyme & Supermolecular Cage

selective substrate bindinginduced proximityhydrophobic interiorcomplex superstructurehard to make

selective substrate bindinginduced proximityhydrophobic interiorcomplex superstructurehard to make

Supermolecular cage:

12 NO3-

12+selective caging by size, shape, etcspace-restricted environmenthydrophobic interiorwell-defined and tunable structure

selective caging by size, shape, etcspace-restricted environmenthydrophobic interiorwell-defined and tunable structure

Natural enzyme:

Approach to Supermolecular Cage

• Synthesis by covalent bonding

• Self-assembly by noncovalent interactions

The Encyclopedia of Twentieth-Century Architecture (Ed.: R.Stephen Sennott),Fitzroy Dearborn, Chicago, 2002.

“Even a common, ordinary brick wants to be something more than it is.”

--Louis Kahn

Self-assembly

- Hydrogen bonding

Self-assembly by Noncovanlent Interactions

- Metal-ligand coordination

fast equilibration / reversible

solvent competition for H-bonding

fast equilibration / reversible

solvent competition for H-bonding

greater strength

more rigidity

stable in aqueous solution

greater strength

more rigidity

stable in aqueous solution

‘Softball’‘Softball’

Kang, J.; Rebek, J., Jr. Nature 1997, 385, 50. Kang, J.; Santamarı´a, J.; Hilmersson,G.; Rebek, J., Jr. J. Am. Chem. Soc. 1998, 120, 7389.

HN N

NHNNN

NN

OH

OH

O

O

O

O

OH

OH

R R

O

O

NHN

N NHRR

O

O

R= 4-n-heptylphenyl

H-bonding Based Supermolecular Cage

Volume = 320 Å3

Functions of Metal-ligand Based Supermolecular Cages

Fujita’s story - molecular triangles

Hupp’s story – molecular squares

Self-Assembly of Molecular Triangle -Fujita’s Story

n

NN

N

N

NN

NN

N

N

NN

N

NN

NN

N

NN

NNN

N

H2N PdNH2

O2NOONO2

http://www.chem.t.u-tokyo.ac.jp/appchem/labs/fujita/paneling.html

NH2

Pd

H2N

Pd =12+, water soluble

Hydrophobic cavity

12+, water soluble

Hydrophobic cavity

M6L4 Host Assembly-Molecular Paneling

12 NO3-

12 NO3-

12 NO3-

N

N

N

N

N

N

Pd

PdPd

N

N

PdPd

Pd

N

N

N

N

12+

‘tube’‘tube’

‘bowl’‘bowl’

‘cage’‘cage’

[2+2] Photodimerization of Olefins within Nanocages

• Poor yield and selectivity in solution phase• Improved reactions need to be conducted in crystalline state• The ‘cage effect’ – restrictions from lattice

2

syn anti

hv +

2

syn anti

hv +D2O

2 mM, 0.5h > 98% yield

Yoshizawa, M.; Takeyama, Y.; Kusukawa, T.; Fujita, M. Angew. Chem. Int. Ed. 2002, 41, 1347.

2hv

+ ++

HT-syn HH-syn HT-anti HH-anti

benzene


150mM

X


2hv

+ ++

HT-syn HH-syn HT-anti HH-anti

D2O


0.5mM, 3h


HT-syn

CDCl3

> 98% yield

[2+2] Cross-Photodimerization

A B A'-A' B'-B'A'-B'hv+syn / anti syn / anti syn / anti

+ +

A'-A' B'-B'A'-B'

syn syn syn

+ +

hv

A B A A B BA B+ + ++ caging

[2+2] Cross-Photodimerization of Olefins within Nanocages

97% yield

2N

O

O2+ +

D2O3hhv,

N

O

O

inert to hvinert to hv

N

O

O+ N

O

O

D2O80oC, 10min

Cage (1eq.)

1 1:

size compatibilitysize compatibility

Yoshizawa, M. Takeyama,Y.; Okano,T.; Fujita M. J. Am. Chem. Soc. 2003, 125, 3243.

N

O

OCDCl3

Yoshizawa, M.; Miyagi, S.; Kawano, M.; Ishiguro, K.; Fujita, M. J. Am. Chem. Soc. 2004, 126, 9172.

Photochemical Oxidation of AlkanesOH

hv

Air, Lewis Acid

OOH

+CH3CN2

Can we do it in a greener way?

12 NO3-

Pd = Pd

4

Shul’pin, G. B.; Nizova, G. V.; Kozlov, Y. N. New. J. Chem. 1996, 20, 1243.


12 NO3-

Pd = Pd

Alkane Oxidation via Photochemical Excitation of Molecular Cage

hvH2O, r.t., 30min

OH

4

12+

OOH

+

1 : 4


12 NO3-

Pd = Pd

Solvent ?Solvent ?

Metal ?Metal ?

Anion ?Anion ?

H2O CH3CN Solid

Pd2+ Pt2+

NO3- PF6

-


Ligand ?Ligand ? N N

N

Substrate ?Substrate ?

hvAr

hvH2O, r.t., 30min

OH

4

12+

Ar

Generate radical in triazine ligand by hvGenerate radical in triazine ligand by hv

e transfer from alkane to L generating R. & L-e transfer from alkane to L generating R. & L-

Trap R. by H2O or O2 releasing productTrap R. by H2O or O2 releasing product

Mechanism of Alkane Oxidation in Photo Reactor

G

H

G'

H

G

H'

hv


12 NO3-

12+


2.6 Å


Close contact is crucial !

No oxidation with nanobowl

Close contact is crucial !

No oxidation with nanobowl

12 NO3-

Metal-ligand Based Supermolecular Cages

Fujita’s story - molecular triangles

Hupp’s story – molecular squares

A Paradigm of Artificial Enzyme -Hupp’s Story

Merlau, M. L.; Mejia, M. del P.; Nguyen, S. T.; Hupp, J. T. Angew. Chem. Int. Ed. 2001, 40, 4239.

Cytochrome P450Cytochrome P450TON = 50

t1/2 = 10 minTON = 50

t1/2 = 10 min

NN

N NMnⅢN N

Cl-NN

N NFeⅡ

R2 R3

R1 R4

R2 R3

R1 R4OOxidant

Catalyst+

Collman, J. P.; Kodadek, T.; Raybuck, S. A.; Brauman, J. I. J. Am. Chem. Soc. 1985, 107, 4343.

Cl Cl ClCl

O

MnⅤMnⅢ

O

MnⅤ

R1

R2R2R1R2R1

O+MnⅢ

[O]

Mechanism for MetalloporphyrinCatalyzed Epoxidation

Collman, J. P.; Brauman, J. I.; Meunier, B.; Hayashi, T.; Kodadek, T.; Raybuck, S. A. J. Am.. Chem. Soc.1985, 107, 2000.

Cl Cl

O

MnⅤ+ MnⅣ MnⅣOMnⅢ

oxo-dimer2 Cl -

Artificial Enzyme from Directed Self-assembly of Molecular Squares

18 Å

Design a cageDesign a cage

14 Å

N

N

N

NNN

NN

Cl(OC)3Re Re(CO)3Cl

Re(CO)3ClCl(OC)3Re

Zn

Zn

Zn

Zn

18 Å


N

NN

N

N

N

MnⅢ

A perfect cavity !A perfect cavity !

Ka=106 M-1Ka=106 M-1

9 Å

18 Å

TON = 500 t1/2 = 3hTON = 500 t1/2 = 3h


NN

N

N

NNN

NN

Cl(OC)3Re Re(CO)3Cl

Re(CO)3ClCl(OC)3Re

Zn

Zn

Zn

Zn

N

MnⅢ

N

N

MnⅢHost +

PhPh

OCatalyst+ PHIOCH2Cl2, r.t.

92%

Artificial Enzyme from Directed Self-assembly of Molecular Squares

Improve the Catalytic Activity of Artificial Enzyme by Enhance the Caging

Ka=107 M-1

TON=1500

Ka=107 M-1

TON=1500

TON= 65TON= 65


NN

N

N

NNN

NN

Cl(OC)3Re Re(CO)3Cl

Re(CO)3ClCl(OC)3Re

Zn

Zn

Zn

Zn

N

MnⅢN NNN

N NMnⅢN N

N

N

PhPh

OCatalyst+ PHIOCH2Cl2, r.t.

92%

Summary

“It’s all about the space…”--Julius Rebek Jr.

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

Louis KahnYale University Art Gallery

1953, New Haven, Connecticut

Louis KahnSalk Institute for Biologic Studies

1965, La Jolla, California

Louis KahnNational Assembly Building1963, Dhaka, Bangladesh

NN

N

N

NNN

NN

Cl(OC)3Re Re(CO)3Cl

Re(CO)3ClCl(OC)3Re

Zn

Zn

Zn

Zn

N

MnⅢ

Acknowledgement Dr. Borhan

Dr. Wagner

Chrysoula, Dan, Jennifer, Jun, Marina, Shang, Sing, Stewart,

Tao, Xiaofei

Yana

Caging Molecules: Catch Me If You Can€¦ · Aida, T. et.al. Angew. Chem. Int. Ed. 2001, 40, 1857. Caging Molecules: Catch Me If You Can ! Xiaoyong Li Department of Chemistry Michigan

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