Radical scavenging behavior of butylated hydroxytoluene against oxygenated free radicals in physiological environments: Insights from DFT calculations

Abstract Butylated hydroxytoluene (BHT) is a synthetic antioxidant widely used as a preservative in foods containing fat, the petroleum industry, and pharmaceuticals. Herein, a systematic investigation of reaction mechanisms and kinetics of BHT initiated by HO • and HOO • radicals in physiological environments has been reported for the first time. The overall rate coefficients were determined according to the QM‐ORSA (quantum mechanics‐based test for overall free radical scavenging activity) procedure at the M06‐2X/6‐311++G(d,p) level of theory. The radical adduct formation has been found to be the decisive mechanism for HO • scavenging in both polar and lipid media with k overall = 1.39 × 10 12 and 1.13 × 10 11 M –1 s –1 , respectively. While this mechanism has no contribution to HOO • scavenging in physiological environments which mainly takes place via the hydrogen atom transfer mechanism ( k overall = 2.51 × 10 5 and 1.70 × 10 4 M –1 s –1 in water and lipid media, respectively). The obtained findings are consistent with the available experimental data, which validates the accuracy of the calculations.