Rensing, Stephan; Arendt, Markus; Springer, Andreas; Grawe, Thomas; Schrader, Thomas:

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

In: Journal of Organic Chemistry (J.Org.Chem.), Jg. 66 (2001) ; Nr. 17, S. 5814-5821
ISSN: 0022-3263
Zeitschriftenaufsatz / Fach: Chemie
Abstract:
The bonding abilities of m-xylylene di-Me bisphosphonate (I) for arginine could be optimized by strengthening p-cation as well as electrostatic interactions. Electron-donating or -withdrawing substituents in the 5-position of I provide exptl. evidence for p-cation interactions, because bonding energies increase by up to 0.6 kcal/mol due to a single benzene-guanidinium interaction. Even more effective is the introduction of a third phosphonate functionality at the correct distance, so that the guanidinium cation is recognized by optimal electrostatic and hydrogen bond interactions. For example, the optimized host mol. tris(phosphonate) deriv. II was synthesized and it bonded arginine half an order of magnitude more efficiently than the parent mol. I. Monte Carlo simulations and NOESY expts. confirmed the expected complex geometries.