Intramolecular H-bonding Effects

on Ion Binding by Aromatic

Amides: An Ab Initio Study
Rubén D. Parra, Ph.D
DePaul University
Chicago, IL
• I. Introduction
• II. F- - amide Interactions
• III. Li+ - amide Interactions
• IV. Cooperativity in Ion-Pair Binding
• V. Summary and Outlook
• VI. References
• VII, Questions
• VIII. Acknowledgments
 Introduction

• The functional group of an amide is an

acyl group (RCO-) bonded to a nitrogen
atom.
• In particular, the amide RCO-NHR’
exhibits amphiphilic properties.
– The C=O group is suitable to interact with
other groups, atoms, or ions deficient in
electrons.
– The N-H group is suitable for interacting with
electron-rich units.
 Introduction

• Ion binding is the process by which a

molecule, called the host, provides one or
more sites to bind an ion, called the guest,
by means of non-covalent interactions.
• Multiple binding sites are usually needed
because non-covalent interactions are
generally weak.
 Introduction
Chelate effect

Ni2+ + 6 NH3  [Ni(NH3)6]2+

G = -51.7 kj/mol

Ni2+ + 3 NH2CH2CH2NH2 
[Ni(NH2CH2CH2NH2)3] 2+
G = -101.1 kj/mol
 Introduction

Macrocyclic Effect
Zn2+ + A  [ZnA]2+ G = -64.2 kJ/mol
Zn2+ + B  [ZnB]2+ G = -87.5 kJ/mol
A B
 Introduction

• Amide-containing ligands have proven valuable in cation and

anion binding. The amide group exhibits amphiphilic
properties with the carbonyl group serving as a suitable
binding site for metal ions, and the N-H group serving as a
binding site for anions.
• Natural and syntethic amides are used for the transport of
ions across bilayer membranes.
• The great solubility in organic solvents usually accompanied
by a diminished solubility in aqueous solution makes amides
appealing for applications in the field of ion-selective
electrodes and liquid-liquid separations
• Additionally, the hydrogen bonding capabilities of amides are
known to be crucial in many relevant systems including
enzymes and proteins.
 Introduction

Positive Cooperativity
Host compounds containing at least two spatially
separated binding sites can show cooperativity
due to conformational coupling between sites.
Comparatively few cases of amphi-receptors
have been reported which show binding
properties to both cations and anions.
 Introduction

• The conventional H bond is usually defined as

X-H … Y
X and Y are typically O, N, F, Cl

• H-bonds are ubiquitous in nature. They are

responsible for the unusual properties of water,
are mediators of chemical reactions, provide for
drug-molecule interactions in the body, and are
important in the structure of DNA.
 F- - Amide Interactions
• R1 = H or NHC=O
• R2 = H or NHC=O

R1 R2

O O

N N
H H

X-
 F--Binding Amides

• DA tA TA
O O O
N H H N N H

O O O O O O
N N N N N N
H H H H H H
 Li+-Binding Amides

• DA tA TA

H H H
N N N
O O O
H
H N N H N N H H N N H
O O O O O O
DA
DA
DA_F
DA_F
tA_F
TA_F
DA
DA
DA_Li
tA_Li
TA
TA_Li
TA_Li
TA_LiF
 O O
• Binding Energies (kcal/mol)
H H

C C Li+ Binding
• Di-amide -109
N N
H H
• Tri-amide -107
O O
• Tetra-amide -107
C C

H
N
F- Binding
N
• Di-amide -114
H H H H
• Tri-amide -120
• Tetra-amide -127

LiF Binding
• Tetra-amide -294
 • H22…O11
O O
H H Li+ Binding
C C • Tri-amide
1.779 Ǻ (1.789 Ǻ)

N
• Tetra-amide
N
H22 H 1.751Ǻ (1.773 Ǻ)
F- Binding
O11 O • Tri-amide
1.721 Ǻ (1.773 Ǻ)
C C • Tetra-amide
1.717Ǻ (1.773 Ǻ)
H LiF Binding
N N • Tetra-amide
1.696 Ǻ (1.773 Ǻ)
H H H H
 • NBO analysis
O
H
O
H • lpO11 *H22N
C C
Li+ Binding
N N • Tri-amide
H22 H
30 (30 kcal/mol)
O11 O • Tetra-amide
C C 34 (29 kcal/mol)
F- Binding
H
N N • Tri-amide
42 (27 kcal/mol)
H H H H
• Tetra-amide
42 (29 kcal/mol)
LiF Binding
• Tetra-amide
48 (29 kcal/mol)
 • NBO Charges
Li+ Binding
• Tri-amide
qO11 = -0.69 (-0.70)
qH22 = +0.50 (+0.47)
• Tetra-amide
O O
H H qO11 = -0.69 (-0.69)
C C
qH22 = +0.50 (+0.47)
N N F- Binding
H22 H
• Tri-amide
O11 O qO11 = -0.76 (-0.69)
C
qH22 = +0.48 (+0.47)
C
• Tetra-amide
H
N
qO11 = -0.76 (-0.69)
N
qH22 = +0.47 (+0.47)
H H H H
LiF Binding
qO11 = -0.75 (-0.69)
qH22 = +0.50 (+0.47)
 • Dipole Moments (Debye)
H
O O
H Li+ Binding
C C

N
• Di-amide 0.9
N
H
H
• Tri-amide 6.2
O O

C C
• Tetra-amide 3.6
H
N N

H H
F- Binding
H H

• Di-amide 2.9
• Tri-amide 4.3
• Tetra-amide 1.1

LiF Binding
• Tetra-amide 11.3
 • N-H Stretching Frequencies
Li+ Binding
• Di-amide
N-H22 = 3769 (3800 cm-1)
• Tri-amide
O O
H
N-H22 = 3517 (3608 cm-1)
H
C C
• Tetra-amide
H 22
N N
H N-H22 = 3487 (3608 cm-1)
O11 O
F- Binding
C C
• Tri-amide
N
H
N N-H22 = 3457 (3617 cm-1)
H H H H • Tetra-amide
N-H22 = 3295 (3608 cm-1)
LiF Binding
N-H22 = 3287 (3608 cm-1)
• F- Binding
H…F
• Di-amide 1.649 Ǻ H
O O
H

• Tri-amide 1.561 Ǻ; 1.679 Ǻ C C

• Tetra-amide 1.585 Ǻ N N
H H

• Li+ Binding O O

O…Li C C

• Di-amide 1.771 Ǻ
H
• Tri-amide 1.762 Ǻ; 1.780 Ǻ N N

• Tetra-amide 1.775 Ǻ H H
H H

• LiF Binding
H…F 1.588 Ǻ
O…Li 1.770 Ǻ
• F- Binding
NCCC (degs.)
• Di-amide 7 O
O
• Tri-amide 5 H H

C C
• Tetra-amide 4
N N
H H

• Li+ Binding
O O
CNCC (degs.)
• Di-amide 47 C C

• Tri-amide 31, 34
H
• Tetra-amide 22 N N

H H H H

• LiF Binding
NCCC 9
CNCC 24
• NBO analysis: E2 (kcal/mol)
Lp F-  * N-H, * C-H
• Di-amide 197 O O
H
• Tri-amide 187 H
C C
• Tetra-amide 193
N N
H H
• Li Binding
+

Lp O  Li+ O O

• Di-amide 45 C C

• Tri-amide 43
• Tetra-amide 41 H
N
N

• LiF Binding H H H H

Lp F-  * N-H, * C-H 204

Lp O  Li+ 48
Symmetric Stretching frequencies
• F- Binding
N-H + C-H O
O
• Di-amide H
3304 cm-1 H
C C
• Tri-amide 3327 cm-1
• Tetra-amide 3205 cm-1
N N
H H

• Li+ Binding O O
C=O
C
• Di-amide 1813 cm-1 C

• Tri-amide 1814 cm-1

H
• Tetra-amide 1801 cm-1 N N

H H
• LiF Binding H H

N-H + C-H 3216 cm-1

C=O 1784 cm-1
 Summary
• Anion (F-) and cation (Li+) binding through
aromatic amides has been presented.
• Ion binding results in substantial changes in the
equilibrium conformation of the amide model
systems.
• Binding affinity of the anion is greater than that
of the cation.
• Intramolecular H-bonding enhances F- binding,
but has negligible effect on the binding energy of
Li+.
 Summary
• The presence of either ion induces significant
polarization on the ligand. There is charge transfer from
the anion to the ligand, and from the ligand to the metal
ion.
• Charge separation is notorious in the ion-pair binding
which presents the largest dipole moment.
• Evidence of positive cooperativity is presented, where
binding of an ion at one site enhances significantly the
affinity of the ligand for the other ion at the
corresponding binding site.
• Binding of one ion induces conformational changes
along with polarization of the ligand, which is transmitted
to the second binding site.
 References

• R. D. Parra, B. Yoo, M. Wemhoff,   J. Phys. Chem. A. 110, 4487 (2006).

• Bianchi, A.; Bowman-James, K.; Garcia-Espana, E., Eds.
Supramolecular Chemistry of Anions; Wiley-VCH: New York, 1997.
• Saenger, Jeffrey G. A. Hydrogen Bonding in Biological Structures;
Springer-Verlag: Berlin, 1991.
• Kavallieratos, K.; Bertao, C. M.; Crabtree, R. H. J. Org. Chem., 1999, 64,
1675.
• Constable, E. C. Metals and Ligand Reactivity (VCH Publishers, New
York, 1996).
• Desiraju, G. R.; Steiner, T., The Weak Hydrogen Bond In Structural
Chemistry and Biology; Oxford University Press, 1999.
• Wheeler, O. H.; Rosado, O. in The Chemistry of Amides, Interscience
Publishers, 1970, p. 352.
• Schneider, H-J; Yatsimirsky, A. Principles and Methods in
Supramolecular Chemistry; Wiley, Chichester, 2000.
• Steed, J. W.; Atwood, H. L.; Supramolecular Chemistry; Wiley,
Chichester, 2000.
 Acknowledgments

• Megan Ghorbanpour
• Michael P. Wemhoff
• Paul D. Kofoed
• Lucia Petkovic and Idaho National Laboratory for
the invitation