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

1. Ion Affinity of a Model Macrocyclic Tetraamide: an Ab Initio Study Rubén D. Parra, Ph.D Department of Chemistry DePaul University, Chicago

2. 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

3. Host-Guest Complexation • “A host-guest relationship involves a complementary stereoelectronic arrangement of binding sites in host and guest…The host component is defined as an organic molecule or ion whose binding sites converge in the complex…The 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.

4. 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

5. Chelate effect complexes of polydentate ligands are more stable than those containing an equivalent number of monodentate ligands. Ni2+ + 6 NH3 [Ni(NH3)6]2+ DG = -51.7 kj/mol Ni2+ + 3 NH2CH2CH2NH2 [Ni(NH2CH2CH2NH2)3] 2+ DG = -101.1 kj/mol

6. 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.

7. Macrocyclic effect Zn2+ + A  [ZnA]2+ DG = -64.2 kJ/mol Zn2+ + B  [ZnB]2+ DG = -87.5 kJ/mol A B

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

9. Macrocyclic tetraamides • Macrocyclic ligands containing four amide (NHC=O) functionalities separated by suitable bridging units.

10. 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.

11. Macrocyclic tetraamidesstudied in this work cation binding anion binding

12. Fluoride binding: Free ligand

13. Fluoride binding: Free ligand

14. Fluoride binding: Complex

15. Fluoride binding: Complex

16. Chloride binding: Complex

17. Chloride binding: Complex

21. Lithium ion binding: Free ligand

22. Lithium binding: Free ligand

23. Lithium ion binding: Complex

24. Lithium ion binding: Complex

28. Ion-pair binding

29. Ion-pair binding: Free ligand

30. Ion-pair binding: Free ligand

31. Ion-pair binding: Ion-pair complex

32. Ion-pair binding: Li+ complex

33. Ion-pair binding: F- complex

35. Intramolecular H-bonding Effects1

36. Intramolecular H-bonding Effects2a

37. Intramolecular H-bonding Effects2b

38. Intramolecular H-bonding Effects2c

39. Intramolecular H-bonding Effects3

40. Intramolecular H-bonding Effects4

43. 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.

44. Summary • In particular, the free ligand (in the case of Li+ complexation) is stabilized by two N-H…O=C 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.

45. 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.

46. 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

47. 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.