A theoretical study of salicylate oxidation for ADME prediction

Abstract

The salicylic acid oxidation has been explained by a mechanism involving single electron transfer oxidation and single hydrogen transfer using quantum chemistry calculations at the B3LYP theory level, together with the 6-311G** basis set. These methods were employed to obtain energy (E), ionization potential (IP), bond dissociation energies (BDE), and spin density distribution of the salicylic acid. The results show no discrepant behaviors between electron and hydrogen transfer in the regioselective hydroxylation of salicylic acid by cytochrome P-450. The unpaired electron remains localized on the O 7 phenolic oxygen (0.26 and 0.38), C 1 carbon atoms at the carbonyl group (0.12 and 0.28), C 2 carbon atom at the hydroxyl group (0.15 and 0.00), C 3 carbon atom at the hydroxyl group (0.22 and 0.30), and C 5 carbon atom (0.40 and 0.41) for cation free radical and semiquinone form, respectively.Calculations of spin densities showed that chemistry reactivity is more favored in the positions C 5 [ C 3 [ C 1 to form salicylate derivatives. These results supported the salicylic acid as scavenger derivatives in the lipid peroxidation. Furthermore, we suggest a conventional proton and secondary electron abstraction, and semiquinone form by [1,5] hydrogen shift between phenol and carbonyl groups.

Stability and Reactivity of Benzopyranones Derivatives

“…Further, the stability of the compounds can be observed by spin densities distribution. [23][24][25][26][27][28][29][30] The calculated spin density to initial electron abstraction (see Fig. 5) shows more contribution from the oxygen of carbonyl moiety for the 4 derivative (0.29), followed of 1 and 2 derivatives (0.27 and 0.26), and 3 derivative (0.16).…”

An Electronic Study for Metronidazole Metabolism

“…[6][7][8] More recently, a model for aromatic oxidation has been proposed. 1 2 9 10 In this study, we report the MTZ reduction by electron transfer to a useful degree of accuracy.…”

“…The regions of positive electrostatic potential indicate excess positive charge, leading to repulsion of the positively charged test probe, while regions of negative potential indicate areas of excess negative charge, leading to attraction of the positively charged test probe. The visualization of all quantum calculations results was performed with Molekel 4.2 17. …”