Analysis of Glyoxilide Therapy and Curriculum Vitae Of Tom Henshaw, Retired Physical Chemist

His career was notable for the development of numerous important technologies from lasers to nanoparticles. Here is his analysis of Dr. William F. Koch's Glyoxilide treatment for cancer.

Dr. William F Koch, due to numerous legal and other attacks, never fully published his formula or method of making Glyoxilide, a treatment he devised for treating cancer in the 1910’s. I asked a veteran, expert chemist to review his published papers and letters which left some clues in order to better understand the mechanisms of action of his clearly effective and often curative treatment for cancer.

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Tom Henshaw is a retired physical chemist (PhD), with over 35 years of research and development experience. He specialized in broad-based scientific and technology innovation in the arenas of physical chemistry, bioscience, and energy. When he was presented with a problem, he liked to develop new approaches for solving it and create technology to implement those solutions. He wrote some papers, published some patents and earned some awards along the way.

He summarized his background/credentials below.

Education

B.A. Chemistry, University of Colorado, Boulder, 1980

PhD. Physical Chemistry,University of Denver, 1987

Work History

Consilium Consulting, 2016 – 2022

Pioneer Astronautics, 2011 – 2015

Directed Energy Solutions/Neumann Systems Group, 2000 - 2011

US Air force Research Laboratory, Directed Energy Laboratory, 1995-2000

National Jewish Health, Infectious Disease Pharmacokinetics Laboratory, 1992-1995

US Air Force Academy, National Research Council Postdoctoral Fellowship, 1988- 1992

The Background Science That Binds It All Together

Chemical kinetics, reaction mechanisms, thermodynamics, and spectroscopy

Interesting Projects I Have Worked on Over the Years

Development of a nanoemulsion for topical drug delivery

Development of a nanoparticle-based Photocatalytic Oxidation Reactor for NASA Environmental Control and Life Support Systems

Development of a mobile biomass-based gasification process for CO₂ - Enhanced Oil Recovery

Development and demonstration of a chemical based laser for the US Air Force

Design, fabrication and demonstration of a novel carbon and acid gas capture system for the exhaust gas produced from coal and gas combustion

Diagnostic development for measuring the pharmacokinetics of drug absorption in TB and AIDS patients

Patents

inventor on numerous patents on the topics named above

Publications

Numerous peer reviewed papers, presentations, technical reports on the topics named above

Awards

Team recipient of the Colorado Springs Economic Development Corp. Award for Technical Innovation (NSG Pollution Control System), 2008 and 2009

Industrial Advisory Board Member, Department of Mechanical and Materials Engineering, University of Denver, 2008-2010

Runner-up for the national 2000 US Air Force Basic Research Award for the development of the All Gas Phase Iodine Laser (AGIL)

Team recipient of the Air Force Research Laboratory Directed Energy Annual Giller Award for excellence in laboratory research, 2000

Funding Awards

Grants and contracts from DOD, DOE, EPA, NASA

Best Regards,

Tom

HENSHAWS ANALYSIS OF KOCH’s THERAPY:

Hi Pierre,

The Koch webpage presents an insightful overview of Dr. Koch's research on oxidative therapy. I also find the readings to be somewhat ambiguous and difficult to follow. This is partially because the writings are over a century old, and the terminology used at that time differs significantly from contemporary descriptions of chemical and biological reactivity. Additionally, the reproduction and resolution of the chemical drawings are suboptimal, further complicating comprehension. In this document, I will attempt to elucidate his proposed oxidation catalysts and reactivity from a chemist's perspective. Please note that I will not delve into or evaluate the medical or therapeutic case studies, as these fall outside my area of expertise.

Dr Koch’s Oxidation Catalysts

Here I’ll try to distill some of what Dr Koch was proposing regarding the oxidation process. He seems to be focusing on small carbonyl (>C=O) substituted ethylene (H2-C=C-H2) or allene-like (H2-C=C=C-H2) compounds. Dr Koch basically identifies an arsenal of five “catalysts” that mediate the oxidation process. These are “Glyoxylide”, O=C=C=O; “Malonide”, O=C=C=C=O, Ketene, H2C=C=O; “Lactene”, H2C=C=C=O; and 1,4-Benzoquinone (or p-quinone), O=Ar=O, where the Ar is denoted as a six-carbon aromatic ring structure. They all have carbonyl groups which are strong electrophiles (electron deficient, thus electron seekers) which react with electron rich targets (chemists call them nucleophiles). All these molecules are unstable except for quinone. The quotation marks are the names he used but today they are called ethylenedione and carbon suboxide for Glyoxylide and Malonide, respectively. I am not sure what Lactene is called today (not an organic chemist). The ketene and quinone names are unchanged in today’s literature.

My opinion

Straight-chain carbonyl compounds, especially O=C=C=O, are highly reactive. Ethylenedione is classified as a bi-radical with two unpaired electrons. O=C=C=O was proposed by Dr Koch in 1913. Ethylenedione was recently studied through advanced spectroscopy, it has a very short picosecond (~10^-12 sec) lifetime before dissociating into two CO molecules. It has eluded detection for 100 years. Due to its instability, O=C=C=O cannot be stored or transported. It cannot be made under ordinary chemical approaches (sometimes called a thermal route). In Dr. Koch's model, I surmise a parent molecule such as glyoxal or quinone must be delivered directly to the target site, where it decomposes (Dr Koch’s term is dehydrogenates) to release O=C=C=O radical and cause the subsequent oxidative damage. However, its transient nature complicates any detailed spectral, thermal, and kinetic analysis, and thus the confirmation of Dr Koch’s oxidative therapy mechanism and the use of “Glyoxylide”.

I think Dr. Koch was trying to convey that quinone may act as a precursor reactant that forms secondary oxidative intermediates such as ethylenedione or carbon suboxide as noted in his aerobic glycolysis mechanism. These intermediates enhance oxidative decomposition potential by "activating oxygen," making it more reactive to disrupt toxins. Dr. Koch suggested the activated oxygen is in the peroxide form, though no explicit active form is mentioned. Here Dr Koch quotes, “… 1:4 Benzoquinone in catalytic dilutions dehydrates, activates oxygen and is changed to Glyoxylide and Malonide, restoring the oxidations within the tissues to such a vigorous normal that no disease toxins whatever can resist being burned,” (from Clinical Demonstration of the Laws of Chemical Structure that Determine Immunity to Disease, and their Application in the Treatment of Patients 1939).

So that’s Dr Koch’s essence of the oxidative approach to therapy. Note: “burned” is another way of saying oxidation. But how does it chemically work? That answer is given below.

Dr Koch’s Reagent Therapy and How It works

So I came across this explanation from Dr Koch on how his compound works at the website: https://williamfkoch.com/kochs-publications-1950-1967/dr-kochs-explanation-of-the-function-of-his-reagents/ (accessed 2-9-2025). My interpretation follows his explanation below.

SURVIVAL FACTOR IN NEOPLASTIC AND VIRAL DISEASES - 1961

Dr. Koch’s Explanation of the Function of His Reagents:

The compound itself is a chain of carbonyl groups with fairly high molecular weight. Our explanation of its action is that it initiates an oxidation chain reaction by chipping of a hydrogen atom from an exposed carbon atom in the toxin molecule, thus producing a radical, which combines oxygen to form a peroxide radical. This peroxide radical acts upon another toxin molecule in the sane way and it forms another peroxide and so the chain is carried by a peroxide of the toxin and this continues until the poison is all oxidized out of the way.

My Interpretation of Dr Koch’s Reaction Scheme

After 1,4 benzoquinone (referred hereafter as quinone) is administered, it converts to Glyoxylide (also known as ethylenedione). A redox reaction occurs via hydrogen atom abstraction from an exposed carbon in the toxin. Ethylenedione (•C₂O₂•) acts as the oxidant and is reduced by gaining the hydrogen atom (H) from the toxin, while the toxin (abbreviated as H-T, where H is on an exposed carbon atom) acts as the reductant and loses the hydrogen atom to become a reactive radical (T•). This radical reacts with oxygen (O₂) to form a radical peroxide (TO2•), initiating a chain reaction that continuously degrades the toxin (H-T) with TO2• regeneration until depletion. The scheme might look like:

C2O2 + H-T  HC2O2 + T· (C2O2 abstracts an H atom from the toxin H-C-T to form T· radical) (1)

T· + O2  TO2· (toxin radical adds oxygen to form a peroxide radical TO2·) (2)

TO2· + H-C-T  TO2H + T-· (peroxide radical continues chain reaction with the toxin H-T) (3)

T-· + O2  TO2C· (peroxide radical chain reaction continues) (4)

Reactions 1 is the chain initiation step. In this step, C₂O₂ abstracts a hydrogen atom (H•, proton plus one electron) from H-T, leaving behind a toxin radical with its unpaired electron (T•). Both the electron and proton move together in H, unlike electron transfer (ET) reactions like ClO₂ redox where only the electron (e⁻) moves. Reactions 2, 3, and 4 are chain carrier or propagation steps. The chain reaction continues until H-T (the toxin) is depleted or terminated by radical recombination (e.g., TO₂ + TO₂ → T₂O₂; T• + TO₂​• → T=O + TO₂​H; T• + T• → T₂). Once the toxin’s chemical makeup is altered by hydrogen atom abstraction into a radical form, it can no longer perform its intended chemical and biological functions and instead undergoes self-annihilation. A common example of H atom abstraction is lipid peroxidation with the hydroxy radical: Lipid-H + HO• → Lipid• + H₂O. Here the hydroxyl radical (HO•) abstracts H• from a lipid, forming a lipid radical, which then propagates oxidative chain reactions.

Summary. Dr. Koch’s mechanism involves a redox system initiated by a radical H atom abstraction. This triggers a radical chain reaction that consumes the toxin until the reaction stops or the toxin is depleted. He uses compounds that release radical carbonyl compounds to start the redox process or are themselves reactive carbonyls. Quinone, which decomposes into the O=C=C=O radical, appears to be called Glyoxylide. Thus, quinone (and possibly glyoxal) are the key therapeutic compounds, known for their stability and potential medical use. (As you know, various quinones has been used as an agent for anticancer, antibacterial, antiviral, and anti-inflammatory therapies). It's unclear whether quinone or Glyoxylide is specified as the “catalyst”. Are the therapeutic compounds bottled as quinone or Glyoxylide? Glyoxylide is especially transient, difficult to produce chemically, and requires special instruments for detection. The family of "catalysts," including Glyoxylide (O=C=C=O), Malonide (O=C=C=C=O), Ketene (H2C=C=O), and Lactene (H2C=C=C=O), are not suitable for therapeutic use on their own. This is due to their instability, which prevents them from being isolated, stored, or even safely transported within the body to an active site. Therefore, the drug's identity is ambiguous. He mentioned some “catalyst” dilutions ranging from 10^-12 to 10^-30. Without specifying units, if it's molar, that's a very dilute mixture. He calls them catalysts but in the strict definition of a catalyst they are not regenerated but only decomposed in this mechanism. Dr. Koch may refer to these reagents as catalysts because they initiate a radical chain reaction where the toxin and toxin peroxide radicals are continually regenerated in the chain reaction. Quinone may have potential therapeutic utility, but possibly in a different manner.

Quinone and Oxidation Thermodynamics

The quinone family are natural compounds with significant medicinal potential such as antimicrobial, antitumor, antiviral, and anti-inflammatory agents. Quinones are highly reactive electrophiles that can undergo non-enzymatic reactions with various nucleophiles, including thiols, amines, and other electron-rich species. This reactivity arises from the electrophilic nature of the quinone carbonyls, which readily undergo Michael addition and redox cycling. Quinones accept and donate electrons easily, making them reactive in oxidation-reduction (redox) reactions. These include the one-electron reduction to form semiquinone radicals (SQ•⁻), which can react further with nucleophiles. A two-electron reduction forms hydroquinones (H2Q), which may regenerate quinones via oxidation.

In keeping with Dr Koch’s thesis of peroxide formation, let’s look at quinone’s redox reaction with oxygen (O₂) through the mechanism of an electron transfer redox process. I’ll use electrochemical data to establish whether quinone (Q) can thermodynamically reduce O₂ to "activated oxygen," i.e., superoxide (O₂•-), hydroperoxyl radical (HO₂•), and hydrogen peroxide, H₂O₂. If these are favorably formed, it carries a pretty good oxidizing potential to wallop bacteria, viruses and various diseased cells as well as performing cell signaling processes. These reactions are stand-alone redox couples and are not assisted by enzymes or other catalysts like that found in the electron transport chain in mitochondria. The values for the electrochemical reduction potentials for quinone (Q), semiquinone (Q•-), and hydroquinone (H2Q ) are presented at pH 7 and 298K (25 ⁰C) in Table 1 below. Also included are O₂ and the active oxygen forms of superoxide (O₂•-), hydroperoxyl (HO₂•), and hydrogen peroxide (H₂O₂) half reactions. To do this we compare and evaluate the redox potential between the species involved in the reaction and the environment it occurs in (i.e., pH). If the overall redox potential is positive, then the overall reaction is favorable and can proceed spontaneously to products. If the redox potential is negative, the reaction is “uphill” and needs an external energy input to drive the rection to products. These considerations are based on the change in the Gibbs free energy of the system.

Redox Calculations. You don’t have to worry about the calculation details that follow, I’ll put it in plain speak at the end (hopefully!).

Table of Reduction Potentials for Quinone and Oxygen Compounds

Reduction Reaction

E^0’ (V) [pH7, 298K]

Reference

Q + e- ⇌ Q•-

0.099

Song and Buettner (2010)

Q•- 2H⁺ + e- ⇌ H2Q

0.473

Song and Buettner (2010)

Q + 2H⁺ + 2e- ⇌ H2Q

0.286

Song and Buettner (2010)

O₂ + e- ⇌ O₂•-

-0.18

Armstrong et al., 2015

O₂ + H⁺ + e- ⇌ HO₂•

0.1

Armstrong et al., 2015

HO₂• + H⁺ + e- ⇌H₂O₂

1.46

Armstrong et al., 2015

Step

Reduction Half Reactions

E0’ (V)

1. Reduction of O₂ to O₂·- by Q

O2 + e- ⇌ O2•-

-0.18

Q + e- ⇌ Q•-

0.099

Net Reaction

O2 + Q•-  O2•- + Q

E_cell = E_red -E_ox = -0.18 – (0.099) = -0.279

-0.279 V

E^0’ < 0, therefore DG >0, reaction nonspontaneous and unfavorable for O2•- formation

2. Reduction of O₂ to HO₂· by Q

O₂ + H⁺ + e- ⇌ HO₂•

0.10

Q + e- ⇌ Q•-

0.099

Net Reaction

O2 + Q•- + H⁺ ⇌ HO2• + Q

E_cell = E_red -E_ox = 0.10 – (0.099) = 0.001

0.001 V

E^0’ ~ 0, DG ~ 0, reaction is near thermoneutral, close to equilibrium. At lower pH (higher H⁺), system favor products

3. Reduction of O₂ to HO₂· by Q

HO2• + H⁺ + e- ⇌ H2O2

1.460

O2 + Q•- + H⁺ ⇌ HO2• + Q

(the reverse of Net Reaction 2)

0.001

Overall Reaction

O2 + Q•- + 2H⁺ + e- ⇌ H2O2 + Q

E_cell = E_red -E_ox = 1.46 + (0.001) = 1.461

1.461. E^0’ > 0, therefore DG < 0, reaction spontaneous and strongly favorable for H2O2 formation

Results: From the analysis above, when Q is coupled into the O2 electron transfer redox systems it favors the formation of HO2 and H2O2 but not superoxide. (Note: superoxide is favorably formed in the mitochondria electron transport chain but that is because NADH, FADH2, Coenzyme-Q aids in the electron transfer processes). The superoxide is not favorable under these conditions because we have defined a near physiological pH (~7.0), in which protons are available, which protonate superoxide and thus making HO₂• formation more favorable than O₂•⁻. Note that Q acts as a redox catalyst, facilitating electron transfer without being consumed. It is continuously regenerated in the redox cycle. However, if Q is permanently modified through bond breaking or formation, such as by oxidative stress, it ceases to function as a catalyst. This mechanism differs from Dr Koch’s because quinone in the electron transfer mechanism is recycled while quinone in Dr Koch’s mechanism quinone is decomposed into the ethlyenedione radical.

So back to Dr Koch. The role of quinone as a redox mediator is certainly plausible. However, I believe its utility would lie in the electron transport (ET) redox arena rather than H-atom abstraction redox. When quinone was being administered, the benefits might have been due to the ET redox system mentioned earlier or a hybrid system involving enzymes or co-enzymes. (In biological reaction systems, reactions are often coupled, making a thermodynamically unfavorable reaction more favorable when paired with an enzyme or coenzyme.) There are a variety quinone based anti-cancer drugs being used today (probably very expensive compared to quinone).

The reaction O₂ + Q•− + 2H⁺ + e− → H₂O₂ + Q indicates a redox cycling process (i.e., a catalytic system) where semiquinone (Q•−) transfers an electron to molecular oxygen, resulting in the production of hydrogen peroxide (H₂O₂) . Q is then regenerated by oxidation of Q•− and then reduced back to Q•− in follow-on reactions. This type of redox recycling reaction readily occurs in the mitochondria, where quinones, such as ubiquinone (CoQ), are parts of the electron transport chain (ETC). So, this could be broadly consistent with Dr Koch’s view that the quinone is acting like a catalyst but not in the manner he described.

A Therapy in the Future?

This is probably old news to you, and I am probably way out my lane here, but the proposed reaction of Q•⁻ reducing O₂ to form H₂O₂ could be a plausible therapy for redox signaling or oxidative destruction of various pathologies. It is essentially like ROS formation in the ETC at Complex I and III in mitochondria except its externally administered, and in the right doses it could initiate a positive cell signaling or oxidative response. For instance, H₂O₂ formation at low levels can act as a signaling molecule by regulating IL-10 and adaptive stress responses, while at high levels it can cause oxidative stress and mitochondrial dysfunction in diseased cells.

So, could the quinone redox system (Q•⁻ / O₂ / H₂O₂) damage mitochondria in cancer cells? It may be possible through some of the following mechanisms:

1. Redox Cycling and Excessive ROS Generation

• Quinones can undergo redox cycling, alternating between oxidized (Q) and semiquinone radical (Q•⁻) forms generating H2O2. Inside the mitochondria, Q•⁻ can donate electrons to O₂, forming hydrogen peroxide, H2O2: O2 + Q•- + 2H⁺ + e- ⇌ H2O2 + Q. If the cancer cell is deficient in antioxidant defenses, excess H₂O₂ may cause oxidative damage, which could result Mitochondrial dysfunction, DNA damage, Lipid peroxidation, Protein oxidation (Schieber M., and Chandel, N.S., 2014).

2. Disrupting Electron Transport Chain (ETC) and ATP Production

· Quinones linked to Complex I or III can intercept electrons, causing leakage and disrupting the mitochondrial proton gradient. This reduces ATP synthesis, which is vital for cancer cell growth. Disrupting the ATP production can lead to an energy deficit, making cancer cells more susceptible to apoptosis or necrosis. Raimondi V., Ciccarese F, Ciminale V. (2020) Oncogenic pathways and the electron transport chain: a dangeROS liaison. Br J Cancer. 2020 Jan;122(2):168-181.

3. Inducing Ferroptosis (Iron-Dependent Cell Death)

· Some quinones induce ferroptosis, a cell death caused by lipid peroxidation. Given cancer cells' high iron levels, Q may increase ROS generation, react with Fe²⁺ in a Fenton-like reaction, and exacerbate oxidative stress via OH radical formation. This leads to mitochondrial lipid peroxidation, causing mitochondrial rupture and cell death. (Takashi, Y., Tomita, K. et al., 2020).

The quinone redox system may not even have to enter the mitochondria. It could disrupt the cellular machinery by oxidation of the cysteine thiols at the cell membrane (Disulfidptosis), or the GSH/GSSG balance within the cytoplasm.

So that’s it for now. I hope this helps. Please feel free to respond, critique, or throw it in the rubbish bin (😊).

Best Regards,

Tom

References

Armstrong, D. A., Huiea, R.E., Koppenol. W. H., et al. (2015). Standard electrode potentials involving radicals in aqueous solution: inorganic radicals (IUPAC Technical Report). Pure and Applied Chemistry 87(11-12): 1139–1150.

Handbook of Biochemistry and Molecular Biology, 5th Edition, (2018), Lundblad, R. L. and

Macdonald, F. M., Editors; Phys. and Chem. Data, Chapter 71, CRC Press, Boca Raton, Florida.

Raimondi V., Ciccarese F., Ciminale V. (2020) Oncogenic pathways and the electron transport chain: a dangeROS liaison. Br J Cancer. Jan;122(2):168-181.

Schieber M, and Chandel NS. (2014). “ROS function in redox signaling and oxidative stress.” Curr Biol. May 19; 24(10): R453-62.

Song and Buettner, 2010. Free Radic Biol Med, September 15; 49 (6):919-962.

Takashi, Y., Tomita, K. et al., (2020). “Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis,” Free Radical Biology and Medicine, Volume 161,Pages 60-70,

(Optional Read. In a reaction between two atoms or molecules that undergo change by the addition (reduction) or loss (oxidation) of electrons is called a redox couple. The electrical work W (units in Joules, or J) done in a redox reaction can be stated as the product of the total electric charge q (in Coulombs, C) transferred and the electric potential difference E (in V, or J/C), W = q∙E. The total charge q transferred during the reaction is related to the product of the number of moles of electrons n, and the Faraday constant F (96485 C/mol, or J/V⋅mol), or (n∙F). The potential E (V) is the maximum potential that the reaction can produce, and thus the maximum electrical work becomes W_max = q∙E = -nFE, where the negative sign indicates work is done by the system. The Gibbs free energy is the energy available to do work. The Gibbs free energy change, DG, for a redox reaction is the maximum electrical work (i.e. non P∙V work) done at constant temperature and pressure. In a spontaneous, reversible redox reaction the work done on its surroundings is equal to a decrease in the Gibbs free energy change of the system, -DG. It follows that the Gibbs free energy DG is related to the potential E, via DG = -W = -nFE. So, when E is positive DG is negative, and we say the reaction is spontaneous and proceeds without any external energy input and the reaction products are favored over reactants.)