Veronica Forrest-Thomson

Farmer, Gareth

doi:10.1007/978-3-319-62722-9

Cited by 44 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wheland, using the experimental results such as heats of hydrogenation or combustion, estimated that the keto form is more stable by 3 kcal/mol [6,26,27]. The well-known reactions where PG reacts readily as the keto form [2,9,17] seem to support the dominance of the keto tautomer. However, the alkylation can lead to O-or C-substituted products indicating that both 3OH enol and keto form of PG exist [16].…”

Section: Introductionmentioning

confidence: 99%

New theoretical insights on tautomerism of hyperforin—a prenylated phloroglucinol derivative which may be responsible for St. John’s wort ( Hypericum perforatum ) antidepressant activity

Ozimiński

Wójtowicz

2019

Struct Chem

View full text Add to dashboard Cite

The thermodynamic aspects of keto-enol tautomerism of hyperforin were investigated theoretically using density functional theory methods. At the B3LYP/aug-cc-pVTZ//B3LYP/aug-cc-pVDZ level of theory the enol tautomer dominates the tautomeric mixture and the second enol tautomer 1OH-HB has Gibbs free energy higher by 1.2 kcal/mol, despite possessing an intramolecular hydrogen bond. The purely keto tautomer is less stable by 3.3 kcal/mol compared with the 1OH tautomer, which means that the percentage of the keto tautomer in the tautomeric mixture is only about 0.4%. This is a different picture than in the parent compound of hyperforin-the phloroglucinol, where the keto tautomer is more stable than corresponding enol 1OH tautomer by 0.6 kcal/mol. To explain this difference, several in-between model molecules reflecting gradual transformation from phloroglucinol to hyperforin were build, and all the tautomeric forms were optimized for each molecule. It turned out that the addition of an aliphatic three-carbon bridge to phloroglucinol ring is crucial for the reversal of the tautomer stability order to that for hyperforin. The probable reason is the unfavorable strain in the keto tautomer introduced by the carbon bridge, which forces a specific geometric configuration which destabilizes in consequence the keto tautomer. This picture of hyperforin tautomerism underlines the dominance of enol tautomers, which can be important when studying the antidepressant activity of hyperforin-its interactions with neurotransmitters receptors.

show abstract