A Theoretical Study for Oxidative Metabolism of Acetaminophen

Abstract

The theoretical study of the acetaminophen acid biotransformation mechanism using quantum chemistry calculations at the B3LYP theory level, together with the 6-31 G * basis set were employed to obtain energy (E), ionization potential (IP), bond dissociation energy (BDE) and spin-density distribution. The unpaired electron remains is localized on the O 7 phenolic oxygen (39%), C 3 and C 5 carbon atoms at ortho positions (27% and 26%) and C 1 at para position (33%). A recombination reaction between a hydroxyl radical and the radicalized carbon atoms at ortho and para positions explain the formation of 3-hydroxy-acetaminophen (3HA) and p-benzoquinone (PBQ) plus acetamide as metabolites of PAR. IP showed that 3HA have more antioxidant properties and can be also responsible for its analgesic activity. LUMO value of PBQ is related with N-acetyl-pbenzoquinone-imine (NAPQI), as toxic metabolic.

Surface sulfate modified TiO2 visible light active photocatalyst for complex wastewater purification: Preparation, characterization and photocatalytic activity

“…The main radical is the hydroxyl radical [42], wherewith niacin reacts faster than with other components [28]. Since the degradation rates of phenol, paracetamol and caffeine were lower in the complex sample, therefore these components were degraded mainly by hydroxyl radical which is also confirmed in the literature [23,24,43]. Caffeine reacts with hydroxyl radical only through one reaction pathway [43] while phenol and paracetamol can react with hydroxyl radical through various pathways due to their aromatic structure [23,24].…”

“…thus is able to degrade the different model contaminants through several reaction pathways, such as phenol and paracetamol used in this article [23,24]. The amount of hydroxyl radical produced is critical to the efficiency of a photocatalyst, thus detection of this radical is essential.…”

Density Functional Theory Study on the Formation of Reactive Benzoquinone Imines by Hydrogen Abstraction

“…They show that formation of the phenoxy radical is energetically favored over the Nacetamide radical, based on the stability of the radical or the intermediate of the reaction. [9][10][11][12][13] In this study we use DFT calculations to investigate the hydrogen abstraction mechanism of acetaminophen and related drug compounds to form the reactive quinone-imine compounds reviewed by Orr et al 14 (see the Supporting Information Table S1). These types of calculations have previously been used for studies on other CYP-mediated reaction types like the aliphatic and aromatic hydroxylations and hetero-atom oxidations to explain trends in activation energies.…”

“…The transformation from NAPSQI to NAPQI is not necessarily enzyme-mediated, and in principle various redox systems present in the cells could be involved. − Therefore, the mechanism of oxidation of acetaminophen to NAPQI has been investigated in several theoretical studies using semiempirical, Hartree–Fock (HF), and density functional theory (DFT) methods. They show that formation of the phenoxy radical is energetically favored over the N -acetamide radical, based on the stability of the radical or the intermediate of the reaction. − …”

An Electronic Study of Tocopherol-Ring Regioisomers as Antioxidants

“…Several studies have been shown that antioxidant activity of molecules is related to its hydroxyl (OH) groups which can scavenge free radicals. [22][23][24] The antioxidant activity of depends on the number of phenolic hydroxyl groups and the location of the hydroxyl groups, [15][16][17][18] double bond in conjugation, [25][26][27][28] and the presence of electron-donating groups further enhances this activity. 16 19 22 26 Moreover, the investigations of regioisomers of tocopherol is little limited.…”