The Supramolecular Chemistry Chemistry of Non-covalent Interactions: Host-guest Complexes

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The Supramolecular ChemistryChemistry of
Non-covalent Interactions Host-guest Complexes
Farzad Fani-Pakdel
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Outline

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

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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

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Intermolecular Forces

• Hydrogen bonding (normally 2-5kcal/mol)
• van Der waals ( lt 2 kcal/mol)
• Coulombic

• cation- P

• P-P face to face, edge to face

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Non-covalent interactions are weak !
Agnew. Chem. Int. Ed. 2001, 40, 2382-2426 Leonard
J. Prins, David N. Reinhoudt, Peter Timmerman
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In Vivo
www.ih.navy.mil/environm.htm
http//www.cstl.nist.gov
DNA cooperative bonding Self-assembly
Enzyme Selectivity, Self-assembly
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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
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Chemical level
Molecular assembly!? Human made DNA?
Host-Guest chemistry is an example of
supramolecular chemistry.
Selectivity!? Human made Enzyme?
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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!?
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Host-Guest Chemistry
Host-Guest chemistry is an example of
supramolecular chemistry.
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Calixarenes

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

Calix4arene
Calix8arene
Calix6arene
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Different views of calix4arene
3-7 Å width
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An example for anion receptor
A Host For Anions

• Urea derivative of calix4arene.
• Urea is a strong hydrogen bond donor

Tetrahedron Letters 42 (2001) 1583-1586 V.
Michlova, Ivan Stibor, Czech Republic
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41
80
n-PrI, Cs2CO3 acetone, reflux
HNO3 CH2Cl2/CH3COOH rt
X t-Bu
SnCl22H2O ethanol, reflux
Ph-NCO CH2Cl2 rt
50
98
15

• Complexation With NBu4X
• An Anionic Guest
• X Cl, Br, I, H2PO4, Acetate, Benzoate

Host
Urea -NH- Hydrogen
Host Guest
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NMR Titration
d1
d2
Fast enough
H
HG
G

X
X
H d 1 HGd2
HG
Kf
dx
H HG
H G
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Results
Kf

• Formation constants from 1H NMR
• titration CHCl3 / CH3CN
• selectivity based on the size
• Cl- gt Br- gt I-
• One to one complexation
• Allosteric effect

11 Å
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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.

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An Organomethalic Derivative of Calix4 For
Hosting Anions
Ru(h6-p-cymene)4(calix4arene-2H)X6
X-ray crystal structure
X BF4-, CF3SO3-, PF6-
J. Am. Chem. Soc. 1997 119(27) 6324-6335 J. L.
Atwood, University of Missuri_at_ columbia
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NBu4I / CH3NO2
Color change
Iodide inclusion complex
X BF4-
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NMR Titration

• NaI in water was added to the host (X CF3SO3-)
  
• Anion to host ratio of 201
• 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

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Results
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
Chemical shift (2 - 2.9 ppm)
Concentration of Iodide 0 - 0.025 M For Host
concentration of 0.00125M
10 error
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18-crown-6 ether as a host for Ruthenium-amine
ComplexesSecond Sphere Coordination
Inorganica Chimica Acta 282 (1998) 247-251
Inorganica Chimica Acta 249 (1996)
201-205 Higashi, Fukuoka University, Japan
Isao Ando, Fukuoka
University, Japan
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2
3
Ru(NH3)5(dampy)(PF6)3
Ru(NH3)5(Pz)(PF6)2
(NH3)5 Ru (Pz) Ru(NH3)5(PF6)5
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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
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18-C-6
18-C-6
18-C-6
Ru(II) - Ru(III) 1 3 complex
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Elemental Analysis
Experimental results for H, N, C, Ru elemental
analysis is compared to calculated ones.
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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
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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
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Ru(III) LMCT
Ru(II) MLCT
LUMO
HOMO
LUMO
Metal
Ligand
HOMO
Ligand
Metal
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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 11 for Ru(II) complex.
DA . 100
Mole fraction of complex 0 - 1
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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

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I / m-A
0.0 0.2 0.3
E/volt
Cyclic voltammogram for Ru(II) complex
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After addition of 0.10M crown ether
Ru(III) Ru(II)
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Another example Artificial Enzyme for
Cytochrome P-450
Cyclodextrin
Manganese porphyrin attached to four
b-cyclodextrins
J. Am. Chem. Soc. 1996, 118, 6601-6605 J. Am.
Chem. Soc. 1997, 119, 4535-4536 R. Breslow,
Columbia University
selective, turnover number 4
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Last oneIron Transfer
Second-Sphere Coordination of Ferrioxamine B A
siderophore
Inorg. Chem. 1995 34(4) 928-932. A L.
Crumbliss, Duke University
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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

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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.

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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. 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
• HigashiInorganica Chimica Acta 282 (1998)
  247-251
• 6. Ando Inorganica Chimica Acta 249
  (1996) 201-205
• 7. R. Breslow J. Am. Chem. Soc. 1996, 118,
  6601-6605
• 8. R. Breslow J. Am. Chem. Soc. 1997, 119,
  4535-4536
• 9. A L. Crumbliss J. Am. Chem. Soc. 1997, 119,
  4535-4536

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Acknowledgements

• Jason R. Telford
• Telfords research group
• Joe Malandra
• Department of chemistry, university of Iowa