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

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

Calix[6]arene sulfonate

Calix[6]arene sulfonate

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

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

Molecular Recognition Mechanism

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

Intermolecular Forces Liquids and Solids Solvation Association

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

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

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

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

Hydrogen Bonding Guests arginine 180 lysine

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

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

Conformations for guest-host complexes

Molecular Recognition Mechanism

Guests for Calix[6]arene

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

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

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

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

Acknowledgements *Division of Natural Science and Mathematics, Colby College *National Science Foundation Grant, CCLI #0088307