1. Guest-host complexation
Calix[6]arene sulfonate Host
Chris Millman, Shehan Don Talagala, Cassandra Newell, Galia Debelouchina, Jonathan Lees, Peter Foster, and Tom Shattuck

2. Introduction Molecular Recognition
Guest Host Complex
Questions:
How is selectivity achieved?
What are the forces?
Biological macromolecules: enzyme-substrate

3. Calix[6]arene sulfonate

4. Calix[6]arene sulfonate

5. Guests for Calix[6]arene Sulfonate
arginine Keq = 186
lysine Keq = 94
tetrabutylammonium
benzyltrimethyl ammonium

6. Molecular Recognition Mechanisms
H-bonding
Charge- charge interactions - Salt bridges
Ion-dipole
Dipole-dipole interactions
Hydrophobic interactions
Pi-pi interactions

7. Molecular Recognition Mechanism

8. Intermolecular Forces
Forces responsible for liquids and solids
Between molecules of the same kind
Solvation
Solvent-solute forces
Association
Molecular recognition
Guest-Host
Enzyme-substrate
Drug-protein
Protein-Protein or protein-nucleic acid

9. Intermolecular Forces
Liquids and Solids
Solvation
Association

10. Molecular Recognition
H-bonding:
strength about 20 kJ/mol (varies)
very directional – very selective

11. Molecular Recognition
Charge- charge interactions - Salt bridges
Coulomb Interaction
non-directional - nonselective
Screened by dielectric constant of solvent + - V r - H H + H

12. Salt Bridges in Proteins
enzyme function: enzyme-substrate
drug discovery: drug-enzyme
cellular regulation:
protein-protein
protein-nucleic acid
protein folding

13. Salt Bridges in Proteins
Human salivary a-amylase 1smd.pdb

14. Hydrogen Bonding Guests
arginine
180
lysine

15. Conformations for guest-host complexes
Calix[6]arenesulfonate and arginine

16. Conformations for guest-host complexes
Calix[6]arenesulfonate and arginine

17. Conformations for guest-host complexes

18. Molecular Recognition Mechanism

19. Guests for Calix[6]arene

20. Pi-pi interactions
Favorable interaction: attraction between pi- electrons and sigma-framework
Geometry controlled by electrostatic interactions: minimize repulsions between pi systems

21. Solvation & Molecular Recognition
Guest Host Complex bulk H2O
Questions:
How does aqueous solvation effect binding?
Enthalpy or Entropy?
Desolvation penalty?

22. Solvation & Salt Bridges - Arginine
Stabilizing Destabilizing
buried-strong desolvation penalty
Human salivary a-amylase 1smd.pdb

23. Solvation and Hydrogen Bonding
No net-change in number of H-bonds
Always in competition with solvent

24. Acknowledgements
*Division of Natural Science and Mathematics, Colby College
*National Science Foundation Grant, CCLI #