Structural features of muscimol, a potent GABA(A) receptor agonist, crystal structure and quantum chemical ab initio calculations

Muscimol, a constituent of the mushroom Amanita muscaria, is a semirigid analogue of the inhibitory neurotransmitter 4-aminobutyric acid (GABA). X-ray structure determinations and quantum chemical ab initio calculations (HF/6-31G*) have been carried out on the muscimol zwitterion. The solid-state conformations of the muscimol zwitterion are calculated to be 1.6-2.2 kcal/mol higher in energy than that of the calculated minimum energy structure in vacuo. A comparison of the calculated and experimental structures indicates that the hydrogen bonding network in the solid state significantly affects the geometry of the molecular structure. This conclusion is supported by results of ab initio calculations on binary complexes between muscimol and an ammonium ion and between muscimol and a methoxide anion, simulating observed hydrogen bonding in the crystal structures.