Cigarette smoke contains two types of free radicals: those in the tar and those in the gas phase. The tar phase contains stable radicals, including a quinone/hydroquinone (Q/QH₂) complex, which can reduce oxygen to produce superoxide, hydrogen peroxide, and hydroxyl radicals. These radicals may react with DNA, contributing to toxicity. The gas phase contains more reactive oxygen- and carbon-centered radicals, formed by the oxidation of NO to NO₂, which then reacts with smoke components like isoprene. These radicals may inactivate α₁-proteinase inhibitor (a1PI), a key antiprotease in the lungs. The Q/QH₂ complex in tar is a polymeric, tarry matrix containing quinone, semiquinone, and hydroquinone units. It can interconvert via hydrogen atom exchange and may act as a redox catalyst, influencing oxygen radical levels in the lungs. Tar radicals can also react with DNA, causing covalent binding. Spin-trapping studies show that gas-phase radicals, such as alkoxyl and carbon-centered radicals, are more reactive than tar-phase radicals. These radicals are produced in a steady state via NO oxidation and may contribute to the inactivation of a1PI. The inactivation of a1PI by cigarette smoke is linked to the presence of NO₂ and hydrogen peroxide. NO₂ can react with hydrogen peroxide to generate hydroxyl radicals, which may inactivate a1PI. Additionally, NO₂ can react with alkenes in smoke to form peroxynitrates, which are unstable but may contribute to inactivation. Tar, while reducing overall, can still quench radicals but may contribute to slow inactivation through hydrogen peroxide production. Cigarette smoke also oxidizes thiols, such as cysteine and glutathione, to disulfides. This oxidation can damage enzymes and protective species, contributing to toxicity. Free radicals are implicated in mutagenesis and cancer, as they can cause DNA damage and alter lipid peroxidation. The presence of radicals in smoke, along with their production by smoke components, suggests a role in the carcinogenic effects of smoking. Overall, the free-radical chemistry of cigarette smoke is a key factor in its toxicological effects, including emphysema, cancer, and other diseases.Cigarette smoke contains two types of free radicals: those in the tar and those in the gas phase. The tar phase contains stable radicals, including a quinone/hydroquinone (Q/QH₂) complex, which can reduce oxygen to produce superoxide, hydrogen peroxide, and hydroxyl radicals. These radicals may react with DNA, contributing to toxicity. The gas phase contains more reactive oxygen- and carbon-centered radicals, formed by the oxidation of NO to NO₂, which then reacts with smoke components like isoprene. These radicals may inactivate α₁-proteinase inhibitor (a1PI), a key antiprotease in the lungs. The Q/QH₂ complex in tar is a polymeric, tarry matrix containing quinone, semiquinone, and hydroquinone units. It can interconvert via hydrogen atom exchange and may act as a redox catalyst, influencing oxygen radical levels in the lungs. Tar radicals can also react with DNA, causing covalent binding. Spin-trapping studies show that gas-phase radicals, such as alkoxyl and carbon-centered radicals, are more reactive than tar-phase radicals. These radicals are produced in a steady state via NO oxidation and may contribute to the inactivation of a1PI. The inactivation of a1PI by cigarette smoke is linked to the presence of NO₂ and hydrogen peroxide. NO₂ can react with hydrogen peroxide to generate hydroxyl radicals, which may inactivate a1PI. Additionally, NO₂ can react with alkenes in smoke to form peroxynitrates, which are unstable but may contribute to inactivation. Tar, while reducing overall, can still quench radicals but may contribute to slow inactivation through hydrogen peroxide production. Cigarette smoke also oxidizes thiols, such as cysteine and glutathione, to disulfides. This oxidation can damage enzymes and protective species, contributing to toxicity. Free radicals are implicated in mutagenesis and cancer, as they can cause DNA damage and alter lipid peroxidation. The presence of radicals in smoke, along with their production by smoke components, suggests a role in the carcinogenic effects of smoking. Overall, the free-radical chemistry of cigarette smoke is a key factor in its toxicological effects, including emphysema, cancer, and other diseases.