The Supramolecular Chemistry

Chemistry of Non-covalent Interactions:

Host-guest Complexes

Farzad Fani-Pakdel

Outline

• Definition and keywords

• Comparing chemical and biological systems

• Three host-guest chemistry systems will be fully described

• Applications

• Conclusion

Supramolecular Chemistry?!

Jean-Marie Lehn (Nobel Prize 1987):

“Chemistry of Molecular Assemblies and of the Intermolecular Bond.”

“Chemistry Beyond Molecule”

There is not a good general definition for such a broad field.

Intermolecular Forces

: face to face, edge to face cation-

Hydrogen bonding (normally 2-5kcal/mol)

van Der waals ( < 2 kcal/mol)

Coulombic

Agnew. Chem. Int. Ed. 2001, 40, 2382-2426Leonard J. Prins, David N. Reinhoudt, Peter Timmerman

Non-covalent interactions are weak !

DNA:cooperative bondingSelf-assembly

http://www.cstl.nist.gov

In Vivo

Enzyme:Selectivity, Self-assembly

www.ih.navy.mil/environm.htm

Chemists Interested In Such systems

Early 1970 molecular recognition in biological systems attracted synthetic chemists.

1967 discovery of crown ethers.

(Charles Pederson).

As 0.4% impurity !

[18] crown-6 a host for K+

Host-Guest chemistry is an example of supramolecular chemistry.

Molecular assembly!? Human made DNA

Chemical level

Selectivity!? Human made Enzyme

It will be many years before our understanding of molecular structure becomes great enough to encompass in detail such substances as the proteins, but the attack on these substances by the methods of modern structural chemistry can be begun now, and it is my belief that this attack will ultimately be successful.

Linus Pauling, 1939

No more jobs for Biochemists!

Is it hopeless for a chemist to try to design super-molecules?

Host-Guest Chemistry

Host-Guest chemistry is an example of supramolecular chemistry.

Calixarenes:

macrocycles that are made from phenol or P-tert-butylphenol.

Calix[4]arene Calix[8]areneCalix[6]arene

Different views of calix[4]arene

~ 3-7 Å width

An example for anion receptor:

Urea derivative of calix[4]arene.

Urea is a strong hydrogen bond donor

Tetrahedron Letters 42 (2001) 1583-1586V. Michlova, Ivan Stibor, Czech Republic

A Host For Anions

X= t-Bu

41%

n-PrI, Cs2CO3

acetone, reflux

HNO3

CH2Cl2/CH3COOH

rt

80%

SnCl2·2H2O

ethanol, reflux

98%

Ph-N=C=O

CH2Cl2

rt

50%

Complexation With NBu4X An Anionic Guest

X= Cl, Br, I, H2PO4, Acetate, Benzoate

Host

Host + Guest

Urea -NH- Hydrogen

NMR Titration

G

X X

+

Fast enough

x [H] [HG]

[H] [HG]

f [H] [G]

[HG]

H HG

Kf

Formation constants from 1H NMR

titration CHCl3 / CH3CN

selectivity based on the size

Cl- > Br- > I-

One to one complexation

Allosteric effect

Results

11 Å

Confirming Results With a Model Compound

R= -NH-Ph

Association constants with anions are almost the same for this model as well as the original host.

In the case of Benzoate there is a large change from 1800 to 161000!

If R= Ph ( i.e. amide instead of urea the Kf drops significantly.

model

J. Am. Chem. Soc.; 1997; 119(27); 6324-6335J. L. Atwood, University of Missuri@ columbia

[{Ru(6-p-cymene)}4(calix[4]arene-2H)]X6

An Organomethalic Derivative of Calix[4] For Hosting Anions

X= BF4-, CF3SO3

-, PF6-

X-ray crystal structure

X= BF4-

[NBu4]I / CH3NO2

Color change

Iodide inclusion complex

NMR Titration

NaI in water was added to the host (X= CF3SO3-)

Anion to host ratio of 20:1 The chemical shift related to methylene of the calix shifts down field (higher ppm) EQNMR software was used to find and model association constant. K1 = 51 M-1 for Iodide

The same experiment was done for Chloride, Bromide, Nitrate, Acetate, Hydrogen phosphate and sulfate

Results

Concentration of Iodide 0 - 0.025 M

For Host concentration of 0.00125M

Ch

emi c

al s

hi f

t ( 2

- 2

.9 p

pm

)

Binding Constants in water

anion K1 K2 K3

Cl- 551 8.1 0.05

Br- 133 13.6 0.35

I- 51

NO3 - 49 109 0.06

CH3CO2- 0

H2PO4- 0

SO42- 0

~10% error

18-crown-6 ether as a host for Ruthenium-amine Complexes

Second Sphere Coordination

Inorganica Chimica Acta 282 (1998) 247-251 Inorganica Chimica Acta 249 (1996) 201-205Higashi, Fukuoka University, Japan Isao Ando, Fukuoka University, Japan

[Ru(NH3)5(Pz)](PF6)2

[Ru(NH3)5(dampy)](PF6)3

[ (NH3)5 Ru (Pz) Ru(NH3)5](PF6)5

2+ 3+

Ru(II)1 : 1 complex

Ru(III)1 : 2 complex

Cartoon Scheme of the Adducts

The Crown ether was dissolved in 1,2-dichloroethane and stirred with the metal complex after filtration, Ether was added to precipitate the product.

Hydrogen Bonding between first and second Sphere Coordination

18-C

-6

18-C-6

18-C-6

Ru(II) - Ru(III)1 : 3 complex

18-C

-6

18-C-6

18-C-6

Elemental Analysis

Experimental results for H, N, C, Ru elemental analysis is compared to calculated ones.

IR Spectroscopy

N-H stretching of ruthenium complex shifts 30-70 cm-1 to lower frequency.

C-O-C stretching also observed at lower energy.

After addition of crown ether:

Data confirms hydrogen bonding between H of Ru-NH3 and O of crown ether

400-2500 cm -1 KBr disk, 2500-4000 cm -1 in Nujol

After addition of crown ether:

Ru(II) complex shows a red shift ( lower energy)

Ru(III) complex shows a blue shift (higher energy)

UV-Vis

Solvent = CH3CN

Both complexes have charge transfer

LUMO

HOMO

LUMO

HOMO

Ru(II): MLCT Ru(III): LMCT

Ligand

LigandMetal

Metal

Another application for UV Job plot

Since the Maximum is at 0.5 molefraction of the complex it shows the ratio of crown ether to complex is 1:1 for Ru(II) complex.

Mole fraction of complex 0 - 1

.

10 0

Cyclic Voltammetry

After addition of crown ether

0.0 0.2 0.3

Cyclic voltammogram for Ru(II) complex

E/volt

I /

A

20

Change in diagram after addition of crown ether is an evidence for binding.

reversibe

negative shift of E 1/2 shows that Ru(III) makes a more stable adduct with the crown ether

Ru(III) – Ru(II)

After addition of 0.10M crown ether

Another example :

Artificial Enzyme for Cytochrome P-450

Manganese porphyrin attached to four -cyclodextrins

Cyclodextrin

J. Am. Chem. Soc. 1996, 118, 6601-6605

J. Am. Chem. Soc. 1997, 119, 4535-4536 R. Breslow, Columbia University

selective, turnover number 4

Last one:Iron Transfer

Inorg. Chem.; 1995; 34(4); 928-932.A L. Crumbliss, Duke University

Second-Sphere Coordination of Ferrioxamine B

A siderophore

Application in Chemistry

Detection of environmental contaminations such as nitrates, phosphates, chromate, uranyl and heavy metals.

Catalysis

Separations

Application in Biology

Understanding biochemical systems

electron transfer, ion transfer, enzymes

Design: Artificial enzymes, medicinal applications

Conclusion

• Host-guest chemistry is not limited to some special molecules or hosts. We can have Cations, neutral species, anions and even metal complexes as both host and guest.

• All sort of intermolecular interactions are important.• Host-guest interactions influences the chemical and spectroscopic

properties of both host and the guest.• We can use different analytical methods in order to measure or

estimate the strength of such interactions. Association constant is an important factor in this case.

• Selectivity based on intermolecular forces and geometrical effects was observed.

• Solvent has an important role in these interactions.• Reversibility.

References

1. Supramolecular Chemistry, Jonathan W.Stead, Jerry L. Atwood, (2000) J. Wiley and Sons

2. Leonard J. Prins, David N. Reinhoudt, Peter Timmerman; Agnew. Chem. Int. Ed. 2001 40 2382-2426

3. V. Michlova, I. Stibor; Tetrahedron Letters 42 (2001) 1583-15864. J. L. Atwood; J. Am. Chem. Soc. 1997, 119(27), 6324-63355. Higashi;Inorganica Chimica Acta 282 (1998) 247-251 6. Ando; Inorganica Chimica Acta 249 (1996) 201-2057. R. Breslow; J. Am. Chem. Soc. 1996, 118, 6601-66058. R. Breslow; J. Am. Chem. Soc. 1997, 119, 4535-45369. A L. Crumbliss; J. Am. Chem. Soc. 1997, 119, 4535-4536

Acknowledgements

Jason R. Telford Telford’s research group Joe Malandra Department of chemistry, university of Iowa