STRUCTURE-ACTIVITY RELATIONSHIP OF CHANNEL BINDING-AFFINITY OF QUATERNARY AMMONIUM-IONS

AIM: To explore the structure-activity relationship of quaternary ammo nium (QA) ions at the external binding site of K+ channel. METHODS: In sightII and MOPAC 6.0 molecular modeling package were used to calculat e the free energy of hydration (Delta G(hydration)), the energy of the highest occupied orbital (E-HOMO), and the energy of the lowest unocc upied orbital (E-LUMO) for each QA ion, respectively. The partial leas t square method was used to analyze the relationship between the bindi ng free energy and these descriptive parameters. RESULTS: Generally, t he higher the E-LUMO of a QA ion was, the weaker its solvation was and accordingly the stronger binding affinity. For a QA ion larger than t etraethylammonium (TEA), its large size was unfavorable to its channel binding affinity. CONCLUSION: The binding affinity of all QA ions cor related well with Delta G(hydration) and E-LUMO.