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?!
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”
Intermolecular Forces
 Hydrogen bonding (normally 2-5kcal/mol)
 van Der waals ( < 2 kcal/mol)
 Coulombic
 P-P: face to face, edge to face
 cation- P
Non-covalent interactions are weak !
Agnew. Chem. Int. Ed. 2001, 40, 2382-2426
Leonard J. Prins, David N. Reinhoudt, Peter Timmerman
In Vivo
http://www.cstl.nist.gov
DNA:
cooperative bonding
Self-assembly
www.ih.navy.mil/environm.htm
Enzyme:
Selectivity, Self-assembly
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+
Chemical level
Molecular assembly!?
Human made DNA
Host-Guest chemistry is an example of supramolecular chemistry.
Selectivity!?
Human made Enzyme
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!
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[6]arene
Calix[8]arene
Different views of calix[4]arene
~ 3-7 Å
width
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) 1583-1586
V. Michlova, Ivan Stibor, Czech Republic
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%
 Complexation With NBu4X
An Anionic Guest
Host
X= Cl, Br, I, H2PO4, Acetate, Benzoate
Urea -NH- Hydrogen
Host + Guest
NMR Titration
d1
d2
Fast enough
H
+
HG
G
X
X
dx =
[H] d 1 + [HG]d2
[H] + [HG]
Kf =
[HG]
[H] [G]
Results
 Formation constants from 1H NMR
titration CHCl3 / CH3CN
 selectivity based on the size
Cl- > Br- > I One to one complexation
 Allosteric effect
Kf
Confirming Results With a Model Compound
model
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.
An Organomethalic Derivative of Calix[4] For Hosting Anions
X-ray crystal structure
[{Ru(h6-p-cymene)}4(calix[4]arene-2H)]X6
X= BF4-, CF3SO3-, PF6-
J. Am. Chem. Soc.; 1997; 119(27); 6324-6335
J. L. Atwood, University of Missuri@ columbia
[NBu4]I / CH3NO2
Color change
X= BF4-
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
Binding Constants in water
anion
K1
K2
K3
ClBrINO3 CH3CO2H2PO4SO42-
551
133
51
49
0
0
0
8.1
13.6
0.05
0.35
109
0.06
Concentration of Iodide 0 - 0.025 M
For Host concentration of 0.00125M
~10% error
18-crown-6 ether as a host for
Ruthenium-amine Complexes
Second Sphere Coordination
Inorganica Chimica Acta 282 (1998) 247-251
Higashi, Fukuoka University, Japan
Inorganica Chimica Acta 249 (1996) 201-205
Isao Ando, Fukuoka University, Japan
2+
[Ru(NH3)5(Pz)](PF6)2
3+
[Ru(NH3)5(dampy)](PF6)3
[ (NH3)5 Ru (Pz) Ru(NH3)5](PF6)5
Cartoon Scheme of the Adducts
The Crown ether was dissolved in 1,2-dichloroethane and stirred with the metal comp
after filtration, Ether was added to precipitate the product.
Hydrogen Bonding between first and second Sphere Coordination
Ru(II)
1 : 1 complex
Ru(III)
1 : 2 complex
Ru(II) - Ru(III)
1 : 3 complex
Elemental Analysis
Experimental results for H, N, C, Ru elemental analysis is compared
to calculated ones.
IR Spectroscopy
After addition of crown ether:
 N-H stretching of ruthenium complex shifts 30-70 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
400-2500 cm -1 KBr disk, 2500-4000 cm -1 in Nujol
UV-Vis
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
Ru(III): LMCT
Ru(II): MLCT
LUMO
LUMO
Metal
HOMO
Ligand
HOMO
Ligand
Metal
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.
Mole fraction of complex 0 - 1
Cyclic Voltammetry
After addition of crown ether
 Change in diagram after addition of crown
ether is an evidence for binding.
20
 reversibe
 negative shift of E 1/2 shows that Ru(III)
makes a more stable adduct with the crown
ether
0.0 0.2 0.3
E/volt
Cyclic voltammogram for Ru(II) complex
After addition of 0.10M crown ether
Ru(III) – Ru(II)
Another example :
Artificial Enzyme for Cytochrome P-450
Cyclodextrin
Manganese porphyrin attached to
four b-cyclodextrins
selective, turnover number 4
J. Am. Chem. Soc. 1996, 118, 6601-6605
J. Am. Chem. Soc. 1997, 119, 4535-4536
R. Breslow, Columbia University
Last one:
Iron Transfer
Second-Sphere Coordination of Ferrioxamine B
A siderophore
Inorg. Chem.; 1995; 34(4); 928-932.
A L. Crumbliss, Duke University
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.
2.
3.
4.
5.
6.
7.
8.
9.
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.
2001 40 2382-2426
V. Michlova, I. Stibor; Tetrahedron Letters 42 (2001) 1583-1586
J. L. Atwood; J. Am. Chem. Soc. 1997, 119(27), 6324-6335
Higashi;Inorganica Chimica Acta 282 (1998) 247-251
Ando; Inorganica Chimica Acta 249 (1996) 201-205
R. Breslow; J. Am. Chem. Soc. 1996, 118, 6601-6605
R. Breslow; J. Am. Chem. Soc. 1997, 119, 4535-4536
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