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

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 × 10¹² and 1.13 × 10¹¹ 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 × 10⁵ and 1.70 × 10⁴ 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.