Comparative study of patulin, ascladiol, and neopatulin by density functional theory

Patulin, a secondary metabolite produced by several fungal species, is a potential contaminant of fruit and vegetable products. To better understand the structure and electronic properties of this mycotoxin and its biosynthetic precursors, a density functional theory (DFT) study was performed on conformations of patulin, ascladiol, and neopatulin. Geometry optimization and transition state calculations were carried out using the three parameter B3LYP functional at the 6-311++G∗∗ level of theory. Both aqueous solvation studies using a continuum solvation model and in vacuo calculations resulted in several geometry optimized conformations of patulin within a range 2 kcal/mol. One conformation for each enantiomer was preferred by ∼1 kcal/mol over the other geometry optimized conformations considered. Similar results were found for neopatulin. Multiple conformations of ascladiol possessed favorable intramolecular hydrogen bond interactions. The B3LYP/6-311++G∗∗ results are in agreement with experimentally observed crystallographic data for patulin, and suggest several conformations may be important for structure-activity studies of this mycotoxin and its precursors.