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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