A DFT Study of the Conversion of Ptaquiloside, a Bracken Fern Carcinogen, to Pterosin B in Neutral and Acidic Aqueous Medium

Abstract

The conversion of ptaquiloside (PtQ), a bracken fern (Pteridium aquilinum) carcinogen, to pterosin B (PtB), which is involved in the underlying mechanisms of PtQ genotoxicity and carcinogenicity, has been theoretically studied in aqueous neutral (AN) and acid (AA) media, using DFT methods at the PCM(water)‐B3LYP/6‐31G(d)//B3LYP/6‐31G(d) computational level. The β‐elimination of glucose in AN and four reactive channels (A‐D) defined by as many protonation sites in PtQ were calculated. Activation enthalpy decreases (from 42.0 to 12.6 kcal mol−1) in AA relative to AN suggesting protic catalysis. The most favoured channel A started with protonation of the tertiary O15 hydroxyl of PtQ and SN1 water release with strong stabilisation by the spirocyclopropane ring. Natural population analysis and electron localisation function analysis showed significant electron depopulation of vicinal C−C bonds and the remarkable leaving character of the quaternary carbon, which enhanced the nucleophilic attack of water on the distal methylenes while the glucose fragment was retained. This intermediate was unstable, degrading rapidly to a stable PtB‐glucose‐water‐H+ molecular complex whose calculated electronic spectrum (λmax=271.5 nm) matched the value of an intermediate reported earlier with a different structure. PtQ‐dienone, long assumed as the carcinogenic form of PtQ, is not formed in AA but only and unfavourably so in protonated form assisted by one molecule of water.

Inducing high exo selectivity in Diels–Alder reaction by dimethylborane substituent: a DFT study

“…Along the reaction path (prior to the TS) in a bimolecular reaction, the two reactants may form a molecular complex (MC) in which they are held together by weak intermolecular interactions such as van der Waals (vdW) forces, hydrogen bonding, and LAB interaction [32][33][34][35][36] . If the resulting MC is less stable than the corresponding free reactants (that is, the standard Gibbs free energy change associated with the formation of MC from the reactants is + 3 kcal/mol or higher), then its equilibrium concentration would be much lower than the reactants (< 1% at room temperature) and thus the formation of MC can be practically ignored.…”