Ion Affinity of a Model Macrocyclic Tetraamide: an Ab Initio Study

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Ion Affinity of a Model Macrocyclic Tetraamide
an Ab Initio Study

• Rubén D. Parra, Ph.D
• Department of Chemistry
• DePaul University, Chicago

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Ion Affinity of a Model Macrocyclic Tetraamide
an Ab Initio Study

• I. Introduction
• II. Macrocyclic Tetraamides
• III. Anion -Tetraamide Interactions
• IV. Li-Tetraamide Interactions
• V. Cooperativity in Ion-Pair Binding
• VI. Summary and Outlook
• VII. References
• VIII, Questions
• IX. Acknowledgments

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Host-Guest Complexation

• A host-guest relationship involves a
  complementary stereoelectronic arrangement of
  binding sites in host and guestThe host
  component is defined as an organic molecule or
  ion whose binding sites converge in the
  complexThe guest component is any molecule or
  ion whose binding sites diverge in the complex
  Donald Cram
• Multiple binding sites are needed because
  non-covalent interactions are generally weak.

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What is a macrocycle?

• In the context of molecular recognition or
  host-guest chemistry, a macrocycle can be
  conveniently defined as a cyclic molecule with
  convergent binding groups that are arranged to
  match the functionality of the guest molecule.
• 18-Crown-6 Ether Calixpyrroles

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Chelate effect

• complexes of polydentate ligands are more stable
  than those containing an equivalent number of
  monodentate ligands.
• Ni2 6 NH3 ? Ni(NH3)62
• DG -51.7 kj/mol
• Ni2 3 NH2CH2CH2NH2 ? Ni(NH2CH2CH2NH2)3 2
• DG -101.1 kj/mol

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Macrocyclic effect

• Macrocyclic effect complexes with macrocyclic
  ligands are more stable than those with
  polydentate open ligands containing an equal
  number of equivalent donor atoms.

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Macrocyclic effect

• Zn2 A ? ZnA2 DG -64.2 kJ/mol
• Zn2 B ? ZnB2 DG -87.5 kJ/mol
• A B

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Preorganization

• If a host does not undergo a significant
  conformational change upon guest binding, it is
  said to be preorganized.
• 18-crown-6

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Macrocyclic tetraamides

• Macrocyclic ligands containing four amide (NHCO)
  functionalities separated by suitable bridging
  units.

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Macrocyclic tetraamides

• In this work
• B1 B3 phenyl ring
• B2 B4 ethene group
• There are sixteen (16) possibilities to arrange
  the four amide groups for a given set of bridging
  units, depending on whether the amide group is
  attached to a bridging unit through its amide
  nitrogen or carbon atom.

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Macrocyclic tetraamidesstudied in this work

• cation binding anion binding

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Fluoride binding Free ligand
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Fluoride binding Free ligand
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Fluoride binding Complex
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Fluoride binding Complex
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Chloride binding Complex
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Chloride binding Complex
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Lithium ion binding Free ligand
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Lithium binding Free ligand
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Lithium ion binding Complex
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Lithium ion binding Complex
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Ion-pair binding
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Ion-pair binding Free ligand
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Ion-pair binding Free ligand
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Ion-pair binding Ion-pair complex
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Ion-pair binding Li complex
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Ion-pair binding F- complex
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Intramolecular H-bonding Effects1
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Intramolecular H-bonding Effects2a
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Intramolecular H-bonding Effects2b
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Intramolecular H-bonding Effects2c
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Intramolecular H-bonding Effects3
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Intramolecular H-bonding Effects4
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Summary

• The two neutral macrocycle tetraamides studied in
  this work exhibit pronounced affinity toward
  cations (Li) and anions(F-, Cl-) respectively.
• Size complementarity seems to determine binding
  selectivity for the anions Cl- anion is too
  bulky to be included in the cavity, whereas the
  smaller F- anion fits well.
• Conformational changes upon Li complexation are
  far more pronounced than in F- or Cl-
  complexation.

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Summary

• In particular, the free ligand (in the case of
  Li complexation) is stabilized by two N-HOC
  intramolecular H-bonding interactions. Li
  complexation involves then the breaking of these
  two intramolecular H-bonds.
• Intramolecular hydrogen bonds involving the amide
  oxygens are shown to enhance F- binding. A gain
  of about 4 kcal/mol in the binding energy is
  obtained per H-bond added in the macrocyle.

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Summary

• The existence of two binding cavities, one for
  anion and the other for cation binding, results
  in a sizeable polarization of the ligand. This
  polarization enhances cooperatively the ion-pair
  binding of the ligand.

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References

• (1)
• (a) Lehn, J. M. Supramolecular Chemistry VCH
  Weinheim, 1995.
• (b) Schneider, H-J Yatsimirsky, A. Principles
  and Methods in Supramolecular Chemistry Wiley,
  Chichester, 2000.
• (c) Steed, J. W. Atwood, H. L. Supramolecular
  Chemistry Wiley, Chichester, 2000.
• (d) Dietrich, B. Viout, P. Lehn, J. M.
  Macrocyclic Chemistry VCH, Weinheim, 1993.
• (e) Bianchi, A. Bowman-James, K. Garcia-España,
  Enrique Eds. Supramolecular Chemistry of Anions,
  1997.
• (2) Chmielewski, M. Szumna, A. Jurczak, J.
  Tetrahedron Lett. 2004, 45, 8699
• (3) Chmielewski, M. Jurczak, J. Tetrahedron
  Lett. 2004, 45, 6007.
• (4) Szumna, A. Jurczak, J. Eur. J. Org. Chem..
  2001, 4031

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Acknowledgments

• Mr. Bryan Yoo
• Mr. Mike Wemhoff
• The Chemistry Department at DePaul University.
• The Chemistry Department at Loyola for the
  invitation
• Last but certainly not least, all of you who
  kindly attended the presentation.