Theoretical and experimental NMR studies on muscimol from fly agaric mushroom (Amanita muscaria)

•NMR and ab initio/DFT studies on muscimol are proposed.•The use of high level theoretical modeling could aid interpretation of muscimol structure.•The observed NMR data of muscimol in DMSO are assigned.•The nonionized and NH-forms of muscimol (1:1) in DMSO are proposed.

In this article we report results of combined theoretical and experimental NMR studies on muscimol, the bioactive alkaloid from fly agaric mushroom (Amanita muscaria). The assignment of 1H and 13C NMR spectra of muscimol in DMSO-d6 was supported by additional two-dimensional heteronuclear correlated spectra (2D NMR) and gauge independent atomic orbital (GIAO) NMR calculations using density functional theory (DFT). The effect of solvent in theoretical calculations was included via polarized continuum model (PCM) and the hybrid three-parameter B3LYP density functional in combination with 6-311++G(3df,2pd) basis set enabled calculation of reliable structures of non-ionized (neutral) molecule and its NH and zwitterionic forms in the gas phase, chloroform, DMSO and water. GIAO NMR calculations, using equilibrium and rovibrationally averaged geometry, at B3LYP/6-31G* and B3LYP/aug-cc-pVTZ-J levels of theory provided muscimol nuclear magnetic shieldings. The theoretical proton and carbon chemical shifts were critically compared with experimental NMR spectra measured in DMSO. Our results provide useful information on its structure in solution. We believe that such data could improve the understanding of basic features of muscimol at atomistic level and provide another tool in studies related to GABA analogs.

Graphical abstractHigh level theoretical studies support the NMR experiment and provide new evidence on the form of GABA agonist-muscimol in DMSO solution.Figure optionsDownload full-size imageDownload as PowerPoint slide