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

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

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.

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 EtherCalixpyrroles

Chelate effect complexes of polydentate ligands are more stable than those containing an equivalent number of monodentate ligands. Ni NH 3  [Ni(NH 3 ) 6 ] 2+  G = kj/mol Ni NH 2 CH 2 CH 2 NH 2  [Ni(NH 2 CH 2 CH 2 NH 2 ) 3 ] 2+  G = kj/mol

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.

Macrocyclic effect Zn 2+ + A  [ZnA] 2+  G = kJ/mol Zn 2+ + B  [ZnB] 2+  G = kJ/mol AB

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

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

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.

Macrocyclic tetraamides studied in this work cation binding anion binding

Fluoride binding: Free ligand

Fluoride binding: Complex

Chloride binding: Complex

Lithium ion binding: Free ligand

Lithium binding: Free ligand

Lithium ion binding: Complex

Ion-pair binding

Ion-pair binding: Free ligand

Ion-pair binding: Ion-pair complex

Ion-pair binding: Li+ complex

Ion-pair binding: F- complex

Intramolecular H-bonding Effects 1

Intramolecular H-bonding Effects 2a

Intramolecular H-bonding Effects 2b

Intramolecular H-bonding Effects 2c

Intramolecular H-bonding Effects 3

Intramolecular H-bonding Effects 4

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.

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.

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.

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

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.