In Silico Evaluation of the Radical Scavenging Mechanism of Mactanamide

Abstract

Mactanamide ( MA ) is a diketopiperazine isolated from marine fungi of the genus Aspergillus . This compound is known as a natural antioxidant from experimental studies, yet this activity has not been successfully modeled thus far. In this work, the hydroperoxyl radical scavenging activity of MA was evaluated in the gas phase and physiological environments by thermodynamic and kinetic calculations. The results revealed that the HOO • radical scavenging of MA in the lipid media follows the formal hydrogen transfer mechanism via hydrogen abstraction at the O11–H bond. In the aqueous solution, however, the antioxidant activity follows the sequential proton loss electron transfer mechanism. The rate constant of the HOO • scavenging of MA in the polar environment is about 1045 times ( k overall = 2.23 × 10 6 M –1 s –1 ) higher than that in the lipid medium ( k overall = 2.20 × 10 3 M –1 s –1 ). In polar media, the HOO • radical scavenging activity of MA is therefore 18 times higher than that of Trolox, the reference compound when assessing antioxidant activity. The results presented here align well with the experimental data, validating the mechanistic pathways and thus providing useful insights into the antioxidant activity of MA .

Is natural fraxin an overlooked radical scavenger?

“…Thus, in this section, the kinetics of the FX + HOOc reaction was evaluated for this bond by following the (QM-ORSA) protocol and the M06-2X/6-311++G(d,p) method. 9,10,22 The results are presented in Fig. 2 and Table 2.…”

“…As FX is a phenolic compound, the deprotonation of the OH moieties must be considered in the evaluation of the antioxidant activity in aqueous solution. 9,22 The initial calculation of PA values showed that the site most likely to dissociate is the O7-H bond. Thus, this bond was used to calculate the pK a of FX.…”

“…Thus, this bond was used to calculate the pK a of FX. The pK a was computed following the literature, 22,64 the molar fractions (% A À and % HA) were computed following eqn (12) and the results are shown in Fig. 3.…”

“…9,21 To save computing time, the M06-2X/6-311++G(d,p)//M06-2X/6-31+G(d) method 9,20 was used to calculate the thermodynamic parameters, whereas the kinetic study was performed by the M06-2X/6-311++G(d,p) method. 9,22,23 Solvent effects of water and pentyl ethanoate were modelled by solvation model density (SMD) method. 10,[24][25][26][27][28][29] The bond dissociation enthalpy (BDE), proton affinity (PA) and ionization energy (IE) were calculated as follows.…”

The hydroperoxyl radical scavenging activity of sulfuretin: insights from theory

“…Previous studies showed that the deprotonation of the OH bonds plays a key role in the HOO • antiradical activity of phenolic compounds in the aqueous solution [ 30 , 34 , 49 ]. The spontaneous dissociation of acidic moieties practically eliminates the activation energy barrier of the first step of the SPLET mechanism, simplifying it to direct electron transfer, and for this reason, this pathway can become energetically favoured in aqueous solution for the dissociated species.…”