Optimization of a synthetic arginine receptor. Systematic tuning of noncovalent interactions

The simple arginine binder I could be optimized by strengthening pi -cation as well as electrostatic interactions. Electron-donating or -withdrawing s ubstituents in the 5-position provide experimental evidence for T-cation in teractions, because binding energies increase by up to 0.6 kcal/mol due to a single benzene - guanidinium interaction. Even more effective is the intr oduction of a third phosphonate functionality at the correct distance, so t hat the guanidinium cation is recognized by optimal electrostatic and hydro gen bond interactions. Monte Carlo simulations and NOESY experiments confir m the expected complex geometries. The optimized host molecule 8 binds argi nine half an order of magnitude more efficiently than the parent molecule.