Submitted to: Journal of Molecular Structure (Theochem)
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/31/2011
Publication Date: 2/22/2012
Citation: Appell, M.D., Moravec, D., Bosma, W.B. 2012. Quantum chemical study of the structure and properties of citrinin. Journal of Molecular Structure (Theochem). 38(4):284-292. Interpretive Summary: In this research, we discovered key features of the chemical structure and properties of the mycotoxin citrinin that help elucidate the influence of its structure on methods of detection. Citrinin is a small toxic molecule produced by several fungal species that frequently contaminate agricultural commodities, and the effects of its complex structure on methods of detection are not known. A state-of-the-art computational study on the three dimensional structures of this toxin provided a thorough understanding of its chemical structure, and offer insight into the appropriate methods for studying a host of related natural products. The reported results will be useful to food safety scientists who seek to improve the design and evaluation of materials that detect and interact with citrinin.
Technical Abstract: Citrinin is a well known polyketide mycotoxin produced by fungal species that naturally occur in certain agricultural commodities, including red yeast rice. This toxin possesses complex intramolecular hydrogen bonding interactions which influence its mode of action and selective detection. Detailed structures and electronic properties of three tautomeric forms and fifteen conformers of citrinin were investigated using density functional theory, ab initio, and PM3 calculations at various extended basis sets and levels of theory. The energetic preference of the predominant p-quinone and o-quinone tautomeric forms were dependent on the calculation method. A previously unstudied carboxylic enol tautomer was calculated to be more energetically stable by PM3 methods, and within 2.5 kcal/mol at the B3LYP/6-311++G(2d,2p) level of theory. Fifteen geometry optimized conformers of the p-quinone and o-quinone tautomeric forms had their extended conjugated pi-systems disrupted and were significantly higher in energy (> 10 kcal/mol). COSMO implicit solvation simulations did not significantly reduce energies of these high energy conformers. Calculated bond lengths and NMR chemical shifts matched experimentally observed values. Despite differences in bond nature and connectivity of the tautomers, NBO analysis revealed that the tautomeric forms share similar natural charges and natural election configurations.