Comparison of Chlorine Dioxide, Hydrogen Peroxide, and Ozone: What Reactions Occur When High Concentrations Come into Contact with Body Tissues? By Asking ChatGPT

By Asking ChatGPT

Yesterday, a reader asked me: since chlorine dioxide can be injected into tumors to treat cancer (specifically due to its multiple tumor-shrinking mechanisms and its ability to eliminate inflammation, achieving the goal of curing cancer), do hydrogen peroxide and ozone, as strong oxidants, also have the same potential for treating cancer?

I explained to them that chlorine dioxide has some unique properties that hydrogen peroxide and ozone do not possess. Specifically: ozone and hydrogen peroxide produce oxygen when they come into contact with body tissues, which poses risks if injected into tumors, whereas chlorine dioxide does not produce oxygen. Additionally, it is difficult to achieve high concentrations with ozone, unlike the 2% (20,000 ppm) chlorine dioxide injection I use.

Many people have not taken basic chemistry courses (this is not meant as an insult, just a statement of fact), and they may not understand how the redox reactions that occur when oxidants come into contact with the body can differ so significantly. Below, I have provided the question I asked ChatGPT and the AI's response. Through this AI's explanation, I hope many people can understand this distinction.

Question: Please describe the redox reactions that occur when chlorine dioxide (3000 PPM) comes into contact with body tissues, and provide the chemical equations. Then, replace chlorine dioxide with hydrogen peroxide (3%) and ozone, and describe the redox reactions that occur when each comes into contact with body tissues, along with their respective chemical equations.

GPT-4o：

When oxidizing agents like chlorine dioxide, hydrogen peroxide, or ozone come into contact with body tissues, they typically undergo redox reactions, primarily interacting with biological molecules, such as proteins, lipids, and DNA. These compounds act as oxidizing agents, accepting electrons from biological molecules, damaging cellular components.

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1. Chlorine Dioxide (ClO₂, 3000 PPM)

Chlorine dioxide is a strong oxidizing agent but a relatively selective one. When it contacts biological tissues, its primary redox reactions are with electron-rich biomolecules (e.g., thiols, phenols, amino acids in proteins, or lipids). These reactions involve a transfer of electrons from organic molecules to chlorine dioxide, leading to its reduction and the oxidation of biomolecules.

Redox Reaction Mechanisms:

• Reduction of ClO₂: Chlorine dioxide is reduced to chlorite (ClO2−​) or chloride ions (Cl−) depending on the number of electrons involved.

  2 ClO2+2 e−→2 ClO2−

  or

  ClO2+5 e−+4 H+→Cl−+2 H2O

• Oxidation of Biomolecules: Biological targets such as thiol groups (-SH) in proteins are oxidized to disulfides (-S-), or lipids and DNA may undergo oxidative damage. For example:

  2 R−SH+ClO2→R−S−S−R+H2O+Cl−

Biological Impacts:

• Proteins: Oxidation of thiol groups, disrupting enzyme function.

• Lipids: Lipid peroxidation, impairing membrane integrity.

• DNA: Oxidative damage to bases, causing mutations or strand scission.

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2. Hydrogen Peroxide (H₂O₂, 3%)

Hydrogen peroxide is another potent oxidizing agent that attacks biomolecules. In tissues, hydrogen peroxide decomposes, often catalyzed by enzymes like catalase, to form reactive oxygen species (ROS) such as hydroxyl radicals (⋅OH).

Redox Reaction Mechanism:

• Decomposition into ROS:

  2 H2O2→2 H2O+O2

  In the presence of Fe²⁺ (via Fenton reaction):

  H2O2+Fe2+→⋅OH+OH−+Fe3+

• Oxidation of Biomolecules:

  R−SH+⋅OH→R−S⋅+H2O

  (Radical-mediated damage to thiolated proteins).

Biological Impacts:

• Proteins: Oxidation of thiol or other functional groups that inactivate enzymes.

• Lipids: Initiation of lipid peroxidation.

• DNA: Oxidative damage such as base modifications or strand breaks.

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3. Ozone (O₃)

Ozone is a highly reactive triatomic molecule that oxidizes biomolecules either directly or by decomposing into reactive oxygen species like singlet oxygen (1O2) or radicals.

Redox Reaction Mechanism:

• Decomposition of O₃: Ozone reacts with water at biological pH to form hydroxyl radicals (⋅OH⋅OH) and other reactive oxygen species:

  O3+H2O→2 ⋅OH+O2

• Direct Oxidation Reactions: Ozone can react directly with double bonds in lipids (lipid ozonolysis):

  R−CH=CH−R′+O3→R−CHO+R′−CHO+O2​

• Oxidation of thiols:

  2 R−SH+O3→R−S−S−R+H2O+O2​

Biological Impacts:

• Proteins: Oxidation of thiol/disulfide bonds, impairing function.

• Lipids: Severe lipid peroxidation, creating lipid aldehydes and compromising membrane integrity.

• DNA: Ozone reacts with DNA bases and sugars, causing oxidative base damage and strand breaks.

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Comparison and Risks:

All three agents are potent oxidizers, but their reactivity and selectivity differ:

• Chlorine dioxide tends to be more selective and less likely to produce free radicals compared to hydrogen peroxide and ozone.

• Hydrogen peroxide produces damaging free radicals (especially via Fenton chemistry) and is effective in initiating oxidative damage.

• Ozone is the most reactive and damages lipids and unsaturated biomolecules directly, with profound effects on membranes and DNA.

Each agent can cause cell and tissue damage at sufficient concentrations and prolonged exposures, making them potentially harmful when uncontrolled.

Question: Avoid using free radicals, as these substances themselves are strong oxidants. They can directly destroy cells, and at high concentrations, even if free radicals are produced, continuous redox reactions will still occur.

GPT-4o：

You are absolutely correct. At high concentrations, potent oxidizing agents such as chlorine dioxide (ClO2), hydrogen peroxide (H2O2​), and ozone (O3​) directly oxidize biomolecules without necessarily relying on free radical mechanisms. Here, I will describe the direct redox reactions that these agents undergo upon contact with body tissues, focusing specifically on their chemical behavior as strong oxidizers.

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1. Chlorine Dioxide (ClO₂)

Chlorine dioxide is a selective oxidizer that interacts directly with biomolecules. It oxidizes critical cellular components such as thiol groups in proteins, amines, unsaturated fatty acids, and other electron-rich biological molecules. The reactions generally involve the reduction of ClO2, accompanied by the oxidation of biomolecules.

Chemical Reactions:

• Oxidation of Thiol Groups in Proteins:

  2 R−SH+ClO2→R−S−S−R+H2O+Cl−

  Here, ClO2 oxidizes thiol groups (-SH) into disulfide bonds (-S-), which disrupts protein structure and function.

• Oxidation of Amine Groups: Primary amines (e.g., from amino acids such as lysine) can react directly with ClO2​:

  R−NH2+ClO2→R−NHOH+HCl

  This oxidative modification alters the function of proteins and other biological molecules.

• Oxidation of Lipids (Unsaturated Fatty Acids): Double bonds in unsaturated lipids are oxidized, leading to lipid degradation and compromising cell membranes:

  R−CH=CH−R′+ClO2→R−COH+R′−COH

  This results in the breakdown of lipid bilayers and membrane integrity.

Net Result:

• The reduction of chlorine dioxide can yield chlorite (ClO2−​) or chloride (Cl−), while key biomolecules in tissues are oxidized.

  ClO2+2 e−→ClO2−

  ClO2+5 e−+4 H+→Cl−+2 H2O

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2. Hydrogen Peroxide (H₂O₂)

Hydrogen peroxide, at 3% concentration, is a strong oxidizer capable of directly disrupting biomolecules upon contact with tissues. Its activity is less selective than chlorine dioxide and affects a variety of cellular components.

Chemical Reactions:

• Oxidation of Thiol Groups in Proteins: Similar to chlorine dioxide, hydrogen peroxide oxidizes thiols into disulfides:

  2 R−SH+H2O2→R−S−S−R+2 H2O

  This damages protein structure and enzymatic activity.

• Oxidation of Methionine and Other Sulfur-Containing Groups: Hydrogen peroxide oxidizes methionine residues in proteins to methionine sulfoxide, disrupting protein function:

  R−CH2−S−CH3+H2O2→R−CH2−S(O)−CH3+H2O

• Oxidation of Lipids: Hydrogen peroxide directly interacts with unsaturated fatty acids, oxidizing them and compromising membrane integrity:

  R−CH=CH−R′+H2O2→R−CH(OH)−CH(OH)−R′

• Effect on DNA: Direct oxidation of DNA bases (e.g., guanine) can occur:

  Guanine+H2O2→8-oxoguanine+H2O

  This results in strand breaks and disruption of genetic material.

Net Result:

• Hydrogen peroxide decomposes into water (H2O) and oxygen (O2), leaving behind oxidized cellular components:

  2 H2O2→2 H2O+O2

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3. Ozone (O₃)

Ozone is one of the most aggressive oxidants. Upon contact with biological tissues, it reacts with virtually all cellular components, including proteins, unsaturated lipids, and nucleic acids. Its high reactivity is non-selective, targeting electron-rich sites.

Chemical Reactions:

• Oxidation of Lipids: Ozone reacts with double bonds in unsaturated lipids through ozonolysis, breaking them into smaller aldehydes and organic acids:

  R−CH=CH−R′+O3→R−CHO+R′−CHO

  This process severely damages cell membranes, leading to loss of cellular integrity.

• Oxidation of Proteins: Ozone oxidizes thiol groups in proteins to disulfides or higher oxidation states:

  2 R−SH+O3→R−S−S−R+H2O+O2

  Additionally, ozone can oxidize amine groups:

  R−NH2+O3→R−NHOH+O2

• Effect on DNA: Ozone oxidizes nucleotide bases such as guanine:

  Guanine+O3→8-oxoguanine+O2

  This compromises DNA fidelity and can lead to mutations or strand breaks.

Net Result:

• Ozone is reduced to oxygen (O2​), while cellular components are oxidized, leading to structural and functional damage:

  O3+2 e−+2 H+→O2+H2O

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Comparison of Oxidizing Agents:

Conclusion:

All three oxidizing agents readily undergo direct redox reactions with biomolecules, causing widespread oxidative damage to proteins, lipids, and DNA. At high concentrations, the extent of tissue damage is significant, resulting in loss of structural integrity, enzymatic dysfunction, and genetic damage, depending on the agent used.