A theoretical study of salicylate oxidation for ADME prediction

Autor: C. Nahum Alves, A. P. Salgado Mendes, R. Santos Borges, J. L. Martins do Nascimento, B. H. Souza e Silva
Rok vydání: 2010
Předmět:
Zdroj: Medicinal Chemistry Research. 20:269-273
ISSN: 1554-8120
1054-2523
DOI: 10.1007/s00044-010-9320-7
Popis: 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 O7 phenolic oxygen (0.26 and 0.38), C1 carbon atoms at the carbonyl group (0.12 and 0.28), C2 carbon atom at the hydroxyl group (0.15 and 0.00), C3 carbon atom at the hydroxyl group (0.22 and 0.30), and C5 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 C5 > C3 > C1 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.
Databáze: OpenAIRE
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