1. The Supramolecular Chemistry Chemistry of Non-covalent Interactions: Host-guest Complexes
Farzad Fani-Pakdel

2. Outline Definition and keywords
Comparing chemical and biological systems
Three host-guest chemistry systems will be fully described
Applications
Conclusion

3. Supramolecular Chemistry?!
There is not a good general definition for such a broad field.
Jean-Marie Lehn (Nobel Prize 1987):
“Chemistry of Molecular Assemblies and of the Intermolecular Bond.”
“Chemistry Beyond Molecule”

4. Intermolecular Forces
Hydrogen bonding (normally 2-5kcal/mol)
van Der waals ( < 2 kcal/mol)
Coulombic
cation- P
P-P: face to face, edge to face

5. Non-covalent interactions are weak !
Agnew. Chem. Int. Ed. 2001, 40,
Leonard J. Prins, David N. Reinhoudt, Peter Timmerman

6. In Vivo http://www.cstl.nist.gov www.ih.navy.mil/environm.htm DNA:
cooperative bonding
Self-assembly
Enzyme:
Selectivity, Self-assembly

7. 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+

8. Chemical level
Molecular assembly!? Human made DNA
Host-Guest chemistry is an example of supramolecular chemistry.
Selectivity!?
Human made Enzyme

9. Is it hopeless for a chemist to try to design super-molecules?
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!

10. Host-Guest Chemistry
Host-Guest chemistry is an example of supramolecular chemistry.

11. Calixarenes:
macrocycles that are made from phenol or P-tert-butylphenol.
Calix[4]arene
Calix[6]arene
Calix[8]arene

12. Different views of calix[4]arene
~ 3-7 Å
width

13. An example for anion receptor:
A Host For Anions
Urea derivative of calix[4]arene.
Urea is a strong hydrogen bond donor
Tetrahedron Letters 42 (2001)
V. Michlova, Ivan Stibor, Czech Republic

14. X= t-Bu n-PrI, Cs2CO3 HNO3 acetone, reflux rt SnCl2·2H2O
41%
80%
n-PrI, Cs2CO3
acetone, reflux
HNO3
CH2Cl2/CH3COOH rt
X= t-Bu
SnCl2·2H2O
ethanol, reflux
Ph-N=C=O
CH2Cl2 rt
50%
98%

15. Complexation With NBu4X An Anionic Guest
X= Cl, Br, I, H2PO4, Acetate, Benzoate
Host
Urea -NH- Hydrogen
Host + Guest

16. NMR Titration d1 d2 H HG G + X X [H] d 1 + [HG]d2 [HG] Kf = dx =
Fast enough H HG G + X X
[H] d 1 + [HG]d2
[HG]
Kf =
dx =
[H] + [HG]
[H] [G]

17. Results Kf Formation constants from 1H NMR titration CHCl3 / CH3CN
selectivity based on the size
Cl- > Br- > I-
One to one complexation
Allosteric effect
11 Å

18. 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 !
If R= Ph ( i.e. amide instead of urea the Kf drops significantly.

19. An Organomethalic Derivative of Calix[4] For Hosting Anions
[{Ru(h6-p-cymene)}4(calix[4]arene-2H)]X6
X-ray crystal structure
X= BF4-, CF3SO3-, PF6-
J. Am. Chem. Soc.; 1997; 119(27);
J. L. Atwood, University of columbia

20. Iodide inclusion complex
[NBu4]I / CH3NO2
Color change
X= BF4-
Iodide inclusion complex

21. 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

22. Results Binding Constants in water anion K1 K2 K3Cl Br I NO
CH3CO
H2PO SO
Chemical shift ( ppm)
Concentration of Iodide M
For Host concentration of M
~10% error

23. 18-crown-6 ether as a host for Ruthenium-amine Complexes Second Sphere Coordination
Inorganica Chimica Acta 282 (1998) Inorganica Chimica Acta 249 (1996)
Higashi, Fukuoka University, Japan Isao Ando, Fukuoka University, Japan

24. 2+ 3+
[Ru(NH3)5(dampy)](PF6)3
[Ru(NH3)5(Pz)](PF6)2
[ (NH3)5 Ru (Pz) Ru(NH3)5](PF6)5

25. 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)
1 : 1 complex
Ru(III)
1 : 2 complex

26. 18-C-6
18-C-6
18-C-6
Ru(II) - Ru(III)
1 : 3 complex

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

28. IR Spectroscopy After addition of crown ether:
N-H stretching of ruthenium complex shifts cm-1 to lower frequency.
C-O-C stretching also observed at lower energy.
Data confirms hydrogen bonding between H of Ru-NH3 and O of crown ether
cm -1 KBr disk, cm -1 in Nujol

29. UV-Vis After addition of crown ether:
Both complexes have charge transfer
After addition of crown ether:
Ru(II) complex shows a red shift ( lower energy)
Ru(III) complex shows a blue shift (higher energy)
Solvent = CH3CN

30. Ru(III): LMCT
Ru(II): MLCT
LUMO
LUMO
HOMO
Metal
Ligand
HOMO
Ligand
Metal

31. Another application for UV Job plot
Since the Maximum is at 0.5 mole
fraction of the complex it shows the ratio of crown ether to complex is 1:1 for Ru(II) complex.
DA . 100
Mole fraction of complex 0 - 1

32. Cyclic Voltammetry After addition of crown ether
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 20
I / m-A
E/volt
Cyclic voltammogram for Ru(II) complex

33. After addition of 0.10M crown ether
Ru(III) – Ru(II)

34. Another example : Artificial Enzyme for Cytochrome P-450
Cyclodextrin
Manganese porphyrin attached to
four b-cyclodextrins
J. Am. Chem. Soc. 1996, 118,
J. Am. Chem. Soc. 1997, 119,
R. Breslow, Columbia University
selective, turnover number 4

35. Last one: Iron Transfer
Second-Sphere Coordination of Ferrioxamine B
A siderophore
Inorg. Chem.; 1995; 34(4);
A L. Crumbliss, Duke University

36. 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

37. 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.

38. References
Supramolecular Chemistry, Jonathan W.Stead, Jerry L. Atwood, (2000) J. Wiley and Sons
Leonard J. Prins, David N. Reinhoudt, Peter Timmerman; Agnew. Chem. Int. Ed
V. Michlova, I. Stibor; Tetrahedron Letters 42 (2001)
J. L. Atwood; J. Am. Chem. Soc. 1997, 119(27),
Higashi;Inorganica Chimica Acta 282 (1998)
Ando; Inorganica Chimica Acta 249 (1996)
7. R. Breslow; J. Am. Chem. Soc. 1996, 118,
8. R. Breslow; J. Am. Chem. Soc. 1997, 119,
9. A L. Crumbliss; J. Am. Chem. Soc. 1997, 119,

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