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 Ether Calixpyrroles

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+

G = -51.7 kj/mol

Ni2+ + 3 NH2CH2CH2NH2 [Ni(NH2CH2CH2NH2)3] 2+

G = -101.1 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

Zn2+ + A [ZnA]2+ G = -64.2 kJ/mol

Zn2+ + B [ZnB]2+ G = -87.5 kJ/mol

A B

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.

Amide Amide

AmideAmide

B1

B2

B3

B4

Macrocyclic tetraamides

• In this workB1 = 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 tetraamidesstudied in this work

cation binding anion binding

N NH

O O

H

N NH H

O O

N N

N N

O O

O O

H H

H H

Fluoride binding: Free ligand

Fluoride binding: Free ligand

Fluoride binding: Complex

Fluoride binding: Complex

Chloride binding: Complex

Chloride binding: Complex

Table 1: Anion binding energies (kcal/mol)

Complex F- Tetraamide E1 -1391.762256 -99.8596977 -1291.743346 -103.302 -1391.762256 -99.8596977 -1291.751119 -95.21

Complex Cl- Tetraamide E1 -1752.12121 -460.274726 -1291.73817 -67.972 -1752.12121 -460.274726 -1291.751119 -59.84

1 geometry of the ligand as in the complex.2 geometry of the ligand fully optimized.Energies obtained at the B3LYP/6-31+G(d)//6-31G(d) level.Total energies in Hartrees

Table 2: Relevant structural parameters

Ligand F- Cl-N-H 1.012 1.029 1.024C=O 1.229 1.233 1.232N-C 1.386 1.375 1.376C-H 1.087 1.084 1.081N...N 2.866 2.955 2.985N...N 5.112 4.875 5.005N...N 5.860 5.701 5.828N-H...X 1.840 2.298

166 172N-H-C=O 163 176 167C-H...X 1.931 2.766

151 118Distances in Angstroms, Angles in degrees.

Table 3: Mulliken charges and N-H symmetricstretching modes

Ligand F- Cl-nN-H (cm-1) 3603 3388 3426

charges (au)X -0.49 -0.67

C-H 0.12 0.19 0.15N-H 0.33 0.38 0.37

Lithium ion binding: Free ligand

Lithium binding: Free ligand

Lithium ion binding: Complex

Lithium ion binding: Complex

Table 2: Li+ binding energies (kcal/mol)

Complex Li+ Tetraamide E1 -1299.147904 -7.28459325 -1291.679121 -115.582 -1299.147904 -7.28459325 -1291.70836 -97.233 -1299.147904 -7.28459325 -1291.735942 -79.92

1 geometry of the ligand as in the complex.

2 geometry of the ligand fully optimized (saddle point).3 geometry of the ligand fully optimized (minimum).Energies obtained at the B3LYP/6-31+G(d)//6-31G(d) level.Total energies in Hartrees

Table 4: Relevant structural parameters for Li+ bindingLigand Li+

N-H (o) 1.024N-H (i) 1.012 1.014C=O (i) 1.236 1.237C=O (o) 1.228N-C (i) 1.369 1.370N-C (o) 1.365

C-H 1.083 1.071O...O 4.560 2.655O...O 6.398 3.125O...O 4.435 4.100

C=O...M 2.050121

C-H...M 2.486103

N-H-C=O 180 179

Table 3: Mulliken charges and C=O symmetricstretching modes

Ligand Li+ ComplexnC=O (cm-1) 1770 1743

charges (au)Li+ 0.39C-H 0.17 0.27

C=O (i) -0.53 -0.52C=O(o) -0.51

Ion-pair binding

N N

N N

O O

O O

H HH H

N NH

O O

H

N NH H

O O

Ion-pair binding: Free ligand

Ion-pair binding: Free ligand

Ion-pair binding: Ion-pair complex

Ion-pair binding: Li+ complex

Ion-pair binding: F- complex

Table 3: Ion-pair (Li+, F-) binding energies (kcal/mol)

Complex Li+ F- Tetraamide ELi_F -2458.735173 -7.284593248 -99.8596977 -2351.172607 -262.47

Li_noF -2358.621611 -7.284593248 -2351.160798 -110.58F_noLi -2451.210135 -99.8596977 -2351.183763 -104.59

-47.30

Energies obtained at the B3LYP/6-31+G(d)//6-31G(d) level.Total energies in Hartrees

Intramolecular H-bonding Effects1

Intramolecular H-bonding Effects2a

Intramolecular H-bonding Effects2b

Intramolecular H-bonding Effects2c

Intramolecular H-bonding Effects3

Intramolecular H-bonding Effects4

Table 4: H-bonding effects on F- binding energies

System E(kcal/mol)* E(kcal/mol)**0 -103.30 -95.211 -107.61 -99.302a -111.46 -104.282b -111.76 -103.202c -111.77 -103.313 -115.41 -106.664 -118.58 -109.69

* Geometry of ligand as in complex** Fully optimized ligand

Table 5: Structural parameters and atomic charges for F- binding

charges (au) 0 HB 1 HB 2a HB 2b HB 2c HB 3 HB 4 HBF- -0.485 -0.485 -0.485 -0.484 -0.484 -0.484 -0.484

(N-)H 0.384 0.390 0.390 0.388 0.391 0.387 0.3880.384 0.381 0.390 0.388 0.391 0.389 0.3880.384 0.383 0.383 0.385 0.381 0.391 0.3880.384 0.386 0.383 0.385 0.381 0.382 0.388

(N-)H total 1.536 1.540 1.546 1.546 1.544 1.549 1.552distances (Ǻ)

N-H…F 1.839 1.795 1.791 1.828 1.78 1.768 1.7991.811 1.792 1.829 1.78 1.802 1.7991.841 1.844 1.813 1.867 1.822 1.7991.876 1.843 1.814 1.867 1.841 1.799

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, 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

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.