Molecular structure and conformations of caramboxin, a natural neurotoxin from the star fruit: A computational study

• The molecular structure of caramboxin is investigated with the aid of DFT calculations.
• Two out of seven conformers determine the NMR spectroscopic signature of the toxin.
• A QTAIM analysis of the charge density reveals the nature of the intramolecular interactions in caramboxin.
• Intramolecular OH⋯O/N and CH⋯O/N H-bonds decrease the conformational freedom of the neurotoxin.

Using density functional theory calculations we investigate the molecular structure and conformations of caramboxin, a neurotoxin recently isolated from the star fruit Averroha carambola. Among the seven conformers that exist within an energy window of ∼16.0 kcal/mol, two of them are the most favored ones with an energy difference of less than 2.0 kcal/mol. The computed chemical shifts of these two low-energy conformers are in good agreement with the experimental values determined in deuterated dimethylsulfoxide thus confirming the 2D chemical structure assigned to the neurotoxin. A topological analysis of the theoretical electronic charge density of four caramboxin conformers reveals the existence of intramolecular CH⋯O/N interactions which, in addition to the classical OH⋯O/N H-bonding interactions, contribute to decrease the conformational freedom of the neurotoxin.

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