The role of regioselective hydroxylation on toxicity of diclofenac and related derivatives Ana C. S. P. S. de Jesus, Fernanda M. Costa, Paulo A. P. F. G. das Neves, Fernanda P. A. Melo, Antonio S. Silva, Osmarina P. P. Silva, Cleydson B. R. Santos, Rosivaldo S. Borges Molecular Simulation, 2019 Diclofenac and related derivatives become more toxic after biotransformation reactions in the body by electron or hydrogen transfers. The structure–reactivity study on regioselective hydroxylation of diclofenac acid was elucidated by using quantum chemistry calculations at level of DFT/B3LYP/6-31G(d,p). HOMO, ionisation potential, bond dissociation energy, and spin density distributions were used as chemical reactivity parameters. Also, some properties are related to lumiracoxib and fenclofenac. The higher flexibility of lumiracoxib can be responsible for the increase of COX2 selectivity. Diphenyl-amine moiety is responsible for their potent antioxidant capacity. Chloro atoms have a strong effect under electron transfer capacity when compared to acetic acid group. Hydroxylation for the 5-hydroxydiclofenac is more favoured in either electron or hydrogen transfers. Both hydroxylation increased the electron donation and antioxidant capacity. These properties were observed to the fenclofenac derivatives and can be related to their toxicity by redox mechanism.
N-acetyl-cysteine increases chemical stability of hydroquinone in pharmaceutical formulations: A theoretical and experimental approach Rosivaldo Borges, Fernanda Costa, Tiago Pereira, Renata Araújo, Eduardo Almeida, Albérico da Silva Journal of the Brazilian Chemical Society, 2018 In this study, the chemistry stability of hydroquinone (HQ) was evaluated according to its effects in redox properties and compared to kojic acid (KA). The HQ oxidation was more inhibited by N-acetylcysteine (NAC) than ascorbic acid (AA). These results were elucidated using theoretical methods at the DFT/B3LYP level of theory. All electronic parameters were related between antioxidant performance and highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), HOMO-LUMO value gap (GAP), ionization potential (IP), and phenol or enol bond dissociation energy (BDE OH ) values. However, the interactions between HQ and NAC cannot be related by changing of these electronic parameters. Therefore the high calculated values for electron transfer can be associated to NAC due to polarizability or chelation properties of sulfur moiety.
