Here is wiki page for Fenton chemistry.
Iron(II) is oxidized by hydrogen peroxide to iron(III), forming a hydroxyl radical and a hydroxide ion in the process. Iron(III) is then reduced back to iron(II) by another molecule of hydrogen peroxide, forming a hydroperoxyl radical and a proton. The net effect is a disproportionation of hydrogen peroxide to create two different oxygen-radical species, with water (H+ + OH−) as a by-product.
Fe2+ + H2O2 → Fe3+ + HO• + OH−
Fe3+ + H2O2 → Fe2+ + HOO• + H+
2 H2O2 → HO• + HOO• + H2O
The free radicals generated by this process then engage in secondary reactions. For example, the hydroxyl is a powerful, non-selective oxidant. Oxidation of an organic compound by Fenton's reagent is rapid and exothermic and results in the oxidation of contaminants to primarily carbon dioxide and water.
If you consider what are the by-products of metabolism in biology you will get carbon dioxide and water. Why these two components? The evolution of biology is built from chemistry which is built from physics. If we consider the Fenton chemistry physics as happening at nanosecond speeds then it creates heat and water. Is biology fundamental to the production of water on earth through Fenton chemistry? Are we seeing a process that has evolved in a biological system that has resulted from a template that occurs in physics that is based on the physics of Fenton chemistry?
If we look at the processes in biology that make use of hydroxyl radicals you might like to do you own research. It appears there are biological processes such as fertilization where the egg and sperm fuse to make the embryo requires Fenton chemistry. Phagocytosis can generate hydroxyl radicals and apoptosis (pre-programmed cell death) can use hydroxyl radicals.
Is life itself dependent on hydroxyl radical recycling of biological molecules and is this significant to why life = water? Does the OH* represent a life force energy? There are many questions that this poses. Water contains hydrogen and oxygen as so does the hydroxyl radical. Oxygen is a di-radical system. Radicals are sensitive to electromagnetic radiation and a radical pair mechanism has been implicated in robin navigation through quantum entanglement.
The antimicrobial properties of honey have been attributed to hydroxyl radicals55, which are produced naturally in the human body during apoptosis60 and is involved as a biological recycling system to breakdown biological structures into CO2 and H2O, and ketone bodies, which are regenerative precursors and used by the body to build new structures. This biological recycling system is highly efficient and can result in a complete destruction of pre-existing biological materials (including bacteria and viruses). It is known that hydroxyl radicals55 and photo-Fenton chemistry56 can be used to clean up toxic sites using bio-remediation approaches and they also occurs in the atmosphere and involved in methane breakdown. It is the natural sterilization process that occurs in our environment. The potential use of this short-lived high-energy radicals to stop COVID19 in its tracks is proposed. A potential inhalation solution82. To further support this approach a Manuka honey topical spray has been registered as a medical device on the MEDSAFE WAND database (200218-WAND-6U608H and has been used by several volunteers to demonstrate efficacy and safety when applied to wounds. The suitability of hydroxyl radicals as antimicrobial and antivirals is further demonstrated by Tri-air Developments83 that produced a plasma, UV based hydroxyl radical generating system for killing 99.9999% microorganisms in air for application on aeroplane air ventilation systems. However, the patents on this technology have lapsed and the company folded due to high production costs, despite the efficiency of the technology. The processing costs for the Manuka honey product are considerably less, as it is naturally produced by the bees, therefore a good margin is expected for the production of the spray. This further supports Quantum Technologies Ltd approach to utilize a pro-drug formulation of hydroxyl radicals55 as a form of antiviral therapy in an inhalation format.
This was part of a New Zealand government proposal that I had put forward to create a product that would assist in helping with mitigation of COVID. This was not supported.
The formulation has been produced naturally by bees as part of Manuka honey production and the method used to remove the sugar enables retention of the structure of the colloidal particles65. It is suggested that the humans have had a long prior exposure to these particles which contain a complex array of molecules, both topically in wound dressings and orally through eating Manuka honey, and it is only a new concentrated formulation, with low sugar content, with an alternative route of administration (inhalation) that needs to be evaluated to demonstrate safety and efficacy toward COVID19. Previous use of honey in an inhalation study48 demonstrated reduction of inflammation associated with asthma. This provides further support and reduces the risk associated with inhalation of the product. The potential for a rapid response using this product provides an opportunity to address the period between now and 18 months required for vaccine development and could be given provided under compassionate purposes, given the global crisis at hand concerning COVID19. Quantum Technologies Ltd is confident that this is not only feasible but highly practical approach to addressing this crisis and is New Zealand focused, where our Taonga will be able to be used in New Zealand and developed with national and international expertise to develop a rapid response to the global pandemic.
Quantum Technologies Limited has developed a suitable process for isolating the active ingredient from Manuka honey. The isolation and stabilization of the Manuka honey active ingredient into a topical inhalation antimicrobial and antiviral spray has the potential to be turned into a therapeutic for COVID19.
The hydroxyl radical system has been developed by a US company for remediation after fires.
This product has been approved by the US FDA. This is a green technology similar to what sunlight does in the environment.
The hydroxyl technology has been used to reduce odours in a range of environments. A meat rendering plant has used the technology.
The hydroxyl system is both natural and has been approved for use in medical facilities.
Atmospheric hydroxyls rapidly react with microorganisms and with nearly every organic chemical available. They remove a hydrogen atom and form a cascade of organic radicals that is further oxidized to form peroxy (R-CO-O·) and oxy (R-C-O·) free radicals, which are also good oxidizing and sanitizing agents. These byproducts are stable enough to circulate under the influence of high velocity fans to completely sanitize air, surfaces and porous fabrics in even exceptionally large spaces. This process and technology has been approved by the FDA and Health Canada.
Fenton chemistry is also used for bioremediation of environments. the powerful oxidant the hydroxyl as they outline is both safe for human to be present around these powerful oxidants and it destroys 99.999% of viruses in the atmosphere. This technology is essentially what the sun does to viruses.
As I have shown that hydroxyl radicals are produced by photo-Fenton chemistry in Manuka honey when diluted with water under a microscope and when exposed to UVa light.
The technology has been tested in volunteer case studies to see if the formulation was suitable for nasal delivery in for the potential in allergy reduction. What was seen was potential benefits to reduce allergies. Again, this is in an early stage of development. The mechanism appears to be due to radical chemistry.
As the half-life of the hydroxyl radical in a biology system appears to be around 1 nanosecond (1 billionth of a second), it means the location where the hydroxyl radical is created e.g. phagosome in phagocytosis, means the reactions with the hydroxyl occur in a very localized environment because the half-life is too short for it move too far from the point of its origin.
As a result, the hydroxyl radical Photo-Fenton chemistry results in the hydroxylation of the aromatic ring in the phenolic leading to its hydroxylation of the aromatic ring. OH groups are added to the rings of phenolic compounds in the pollen leading to the production of phenolics and then polymeric glyoxal.
Figure 3: Hydroxyl reaction with plant phenolics in pollen leading to the production of MGO and DHA
Here is what a pollen grain contained when analysed by MS analysis using MALDI TOF MS instrument without the addition of matrix. Considering the phenolics in the pollen can absorb the laser of the MALDI TOF instrument there is no need to add matrix to the pollen grains isolated from Manuka honey. This provides a way to explore pollen maturation within the Manuka honey.
Figure 4: Polymeric glyoxal in pollen isolated from Manuka honey
My hypothesis is that MGO originates from the pollen as part of the pollen germination process. This is what I discovered and it made no sense in terms of the current scientific literature around MGO being generated from DHA in the honey.
In honey, with its high sugar content there is low water availability. What this means is that the DHA is likely in a dimer.
Figure 5: Glyoxal polymer
This is what is proposed to be present in the pollen and generated during Manuka honey maturation. It is an isolated environment within the Manuka honey where water can accumulate as part of the pollen tube generation process and pollen germination. Considering the expansion of the pollen tube from the pollen grain is driven by pressure (CO2 formation) and water is required for the spermatozoa to travel down the pollen tube and into the ovum to form the embryo. This is what I consider to be the reason why the pollen changes its fluorescent properties on storage within the Manuka honey.
Figure 5: Polymer in pollen grain isolated from Manuka honey
It is proposed that photo-Fenton chemistry in the pollen is responsible for the generation of the polymer observed. These are natural processes happening in the Manuka honey due to the pollen.
- Ali ATM, Chowdhury MNH, Humayyd MSA. Inhibitory effect of natural honey on Helicobacter pylori. Tropical Gastroenterology, 12(3): 139-143, 1991
- Ali ATM. Natural honey accelerates healing of indomethacin-induced antral ulcers in rats. Saudi Med J, 16(2): 161-166, 1995
- Allen KL, Molan PC, Reid GM. A survey of the antibacterial activity of some New Zealand honeys. J Pharm Pharmacol, 43: 817-822, 1991
- Armon PJ. The use of honey in the treatment of infected wounds. Tropical Doctor, 10: 91, 1980
- Bauer L, Kohlich A, Hirschweir R, Siemann U, Ebner H, Scheiner O, Kraft D, Ebner C. Food allergy to honey: pollen or bee products? Characterisation of allergenic proteins in honey by means of immunoblotting. J Allergy Clin Immunol, 97(1): 65 – 73, 1996
- Beck BF, Smedley D. Honey and Your Health. 2nd edn, New York: McBride, 1944 Bergman A, Yanai J, Weiss J, Bell D, David MP. Acceleration of wound healing by topical application of honey. Am J Surgery, 145: 374-376, 1983
- Bousquet J, Campos J, Michel FB. Food intolerance to honey. Allergy, 39(1): 73-75, 1984 Brady NF, Molan PC, Harfoot CG. The sensitivity of dermatophytes to the antimicrobial activity of manuka honey and other honey. Pharmaceutical Sciences, 2: 471-473, 1996
- Branicki FJ. Surgery in western Kenya. Ann Royal Coll Surgeons of England, 63: 348-352, 1981 Cavanagh D, Beazley J, Ostapowicz F. Radical operation for carcinoma of the vulvu. A new approach to wound healing. J Obstetrics Gynaecology Brit Cwlth. 77: 1037-1040, 1970
- Deinzer HL, Thomson PA, Burgett DM, Isaacson DL. Pyrrolizidine alkaloids: their occurrence in honey from tansy ragwort. Science, 195(4277): 497-499, 1977 (abstract only)
- Efem SEE. Clinical observations on the wound healing properties of honey. Br J Surg, 75: 679-681, 1988
- Efem SEE. Recent advances in the management of Fournier’s gangrene: preliminary observations. Surgery, 113: 200-204, 1993
- El-Banby M, Kandil A, Abou-Sehly G, El-Sherif ME, Abdel-Wahed K. Healing effect of floral honey and honey from sugar-fed bees on surgical wounds (animal model). Fourth Intern Conf Apiculture in Tropical Climates, Cairo, 1989, pp 46-49
- Emarah MH. A clinical study of the topical use of bee honey in the treatment of some ocular diseases. Bulletin of Islamic Medicine, 2(5): 422-425, 1982
- Farouk A, Hassan T, Kashif H, Khalid SA, Mutawali I, Wadi M. Studies on Sudanese bee honey: laboratory and clinical evaluation. Int J Crude Drug Res, 26(3): 161-168, 1988
- Gupta SK, Singh H, Varshney AC, Prakash P. Therapeutic efficacy of honey in infected wounds of buffaloes. Indian J Animal Sci, 62(6): 521-523, 1992
- Haffejee IE, Moosa A. Honey in the treatment of infantile gastroenteritis. Br Med J, 290: 1866-1867, 1985
- Helbling A, Peter C, Berchtold E, Bogdanov S, Muller U. Allergy to honey: relation to pollen and honey bee allergy. Allergy, 47(1): 41-49, 1992
- Imperato PJ, Traore D. Traditional beliefs about measles and its treatment among the Bambara of Mali. Trop Geogr Med, 21: 62-67, 1969
- Kandil A, El-Banby M, Abdel-Elwahed K, Abou Sehly G, Ezzat N. Healing effect of true floral and false nonfloral honey. J Drug Res Egypt. 17(1-2), 1987
- Kandil A El-Banby M, Abdel-Wahed K, Abdel-Gawwad, Fayez M. Curative properties of true floral and false nonfloral honeys on induced gastric ulcer. J Drug Res Egypt, 17(1-2): 103-106, 1987b
- Kiistala R, Hannuksela M, Makinen-Kiljunen S, Niinimaki A, Haahtela T. Honey allergy is rare in patients sensitive to pollens. Allergy, 50: 844-847, 1995
- Molan PC. The antibacterial activity of honey. 1. The nature of the antibacterial activity. Bee World, 73(1): 5- 28, 1992
- Molan PC. The antibacterial properties of honey. Chem in NZ, pp 10 – 14, July 1995
- Ndayisaba G, Bazira L, Habonimana E, Muteganya D. Clinical and bacteriological results in wounds treated with honey. J Orthopaedic Surgery, 7(2): 202-204, 1993
- Obi CL, Ugoji EO, Edun SA, Lawal SF, Anyiwo CE. The antibacterial effect of honey on diarrhoea causing bacterial agents isolated in Lagos, Nigeria. Afr J Med Sci, 23: 257-260, 1994
- Palmer-Jones T. Poisonous honey overseas and in New Zealand. NZ Med J, 64: 631-637, 1965
- Phuapradit W, Saropala N. Topical application of honey in treatment of abdominal wound disruption. Aust NZ J Obstet Gynaceol. 32(4): 381-384, 1992
- Postmes TJ, Bosch MMC, Dutrieux R, van Baare J, Hoekstra MJ. Speeding up the healing of burns with honey. in Mizrahi A, Lensky Y (eds), Bee Products: Properties, applications and apitherapy. New York, Plenum Press, pp 27-37, 1997
- Salem SN. Honey regimen in gastrointestinal disorders. Bulletin of Islamic Medicine, 2(5): 422-425, 1982
- Somal NA, Coley KE, Molan PC, Hancock BM. Susceptibility of Helicobacter pylori to the antibacterial activity of manuka honey. J Royal Soc Med, 87(1): 9-12, 1994
- Subrahmanyam M. Topical application of honey in treatment of burns. Br J Surgery, 78(4): 497-498, 1991
- Subrahmanyam M. Honey impregnated gauze versus polyurethane film (OpSiteR) in the treatment of burns – a prospective randomised study. Brit J Plastic Surgery, 46: 322-323, 1993
- Subrahmanyam M. Honey-impregnated gauze versus amniotic membrane in the treatment of burns. Burns, 20(4): 331-333, 1994
- Subrahmanyam M. Honey dressing versus boiled potato peel in the treatment of burns: a prospective randomised study. Burns, 22(6): 491-493, 1996
- Subrahmanyam M. A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine. Burns, 24: 157-161, 1998
- Suguna L, Chandrakasan G, Ramamoorthy U, Joseph KT. Influence of honey on collagen metabolism during wound healing in rats. J Clin Biochem Nutr, 14: 91-99, 1993
- Suguna L, Chandrakasan G, Joseph KT. Influence of honey on biochemical and biophysical parameters of wounds in rats. J Clin Biochem Nutr, 13: 7-12, 1992
- Tan ST, Wilkins AL, Molan PC, Holland PT, Reid M. A chemical approach to the determination of floral sources of New Zealand honeys. J Agric Res, 28(4): 212-222, 1989
- Vanderbilt Medical Centre. Infant Botulism. June 1998.
- White JW. Composition of honey. in Crane E (ed). A Comprehensive Survey. Heinemann: London. 1975
- White JW, Riethof ML, Kushnir I. Composition of Honey. VI. The effect of storage on carbohydrates, acidity and diastase content. J Food Sci, 26(1): 63-71, 1960
- White JW, Subers MH. Studies on honey inhibine. 3. Effect of heat. J Apicultural Res, 3(1): 45-50, 1964
- Willix DJ, Molan PC, Harfoot CG. A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey. J Applied Bacteriology, 73: 388-394, 1992
- Wood B, Rademaker M, Molan P. Manuka honey, a low cost leg ulcer dressing. NZ Med J, 110: 107, 1997
- Wootton M, Edwards RA, Faraji-Haremi R, Williams PJ. Effect of accelerated storage conditions on the chemical composition and properties of Australian honeys. 3. Changes in volatile components. J Apicultural Res, 17(3): 167-172, 1978
- Zumla A, Lulat A. Honey – a remedy rediscovered. J Royal Soc Medicine, 82: 384-385, 1989
- Nurfatin Asyikhin Kamaruzaman, Siti Amrah Sulaiman, Gurjeet Kaur, and Badrul Yahaya. Inhalation of honey reduces airway inflammation and histopathological changes in a rabbit model of ovalbumin-induced chronic asthma. BMC Complement Altern Med. 2014; 14: 176.
- Darius Henatsch, Gertjan J.M.den Hartog, Adriaan, Duijvestijn, Petra F. Wolffs, Esther Phielix, Robert J.Stokroos, and Jacob J.Briedéf. (2018). The contribution of α-dicarbonyl compound dependent radical formation to the antiseptic effect of honey. Journal of Functional Foods. Vol 45 pages 239-246.
- Ken Watanabe Ratika Rahmasari, Ayaka Matsunaga,Takahiro Haruyama,and Nobuyuki Kobayashia. (2014). Anti-influenza Viral Effects of Honey In Vitro: Potent High Activity of Manuka Honey. Archives of Medical Research Volume 45, Issue 5, July 2014, Pages 359-365.
- Maryam Alsadat Hashemipour, Zahra Tavakolineghad, Sayed Ali Mohammad Arabzadeh, Zahra Iranmanesh,Sayed Amir Hossein and Gandjalikhan Nassab . (2014). Antiviral Activities of Honey, Royal Jelly, and Acyclovir Against HSV-1. 2014;26(2):47-54.
- Abdel-Naby Awad OG, Hamad AH (2018). Honey can help in herpes simplex gingivostomatitis in children: Prospective randomized double blind placebo controlled clinical trial. Am J Otolaryngol. 2018 Nov - Dec;39(6):759-763.
- Benjamin A. Minden-Birkenmaier, Kasyap Cherukuri, Richard A. Smith, Marko Z. Radic, and Gary L. Bowlin. (2019). Manuka Honey Modulates the Inflammatory Behavior of a dHL-60 Neutrophil Model under the Cytotoxic Limit. International Journal of Biomaterials. Volume 2019, Article ID 6132581, 12 pages.
- Brudzynski K, Lannigan R. Mechanism of Honey Bacteriostatic Action Against MRSA and VRE Involves Hydroxyl Radicals Generated from Honey's Hydrogen Peroxide. Front Microbiol. 2012;3:36. Published 2012 Feb 7. doi:10.3389/fmicb.2012.00036.
- Solís-López, A.Durán-Moreno, F.Rigas, A.A.Morales, M.Navarrete, R.M.Ramírez-Zamora. (2014). Assessment of Copper Slag as a Sustainable Fenton-Type Photocatalyst for Water Disinfection. Water Reclamation and Sustainability 2014, Pages 199-227.
- Majtan J, Bohova J, Prochazka E, Klaudiny J. (2014). Methylglyoxal may affect hydrogen peroxide accumulation in manuka honey through the inhibition of glucose oxidase. J Med Food. Feb;17(2):290-3.
- Matthew Johnston, Michael McBride, Divakar Dahiya, Poonam Nigam (2018). Antibacterial activity of Manuka honey and its components: An overview. Aims Microbiology, 4(4), 655-664.
- Hosokawa Y, Tanaka L, Kaneko M, Sakakura Y, Tsuruga E, Irie K, Yajima T. (2002). Apoptosis induced by generated OH radicals inside cells after irradiation. Arch Histol Cytol. Oct;65(4):301-5.
- Marco Minella, Giulia Marchetti, Elisa De Laurentiis, Mery Malandrino, Valter Maurino, Claudio Minero, Davide Vione, Khalil Hanna (2014). Photo-Fenton oxidation of phenol with magnetite as iron source. Applied Catalysis B: Environmental. Volumes 154–155, July–August 2014, Pages 102-109
- Katrina Brudzynski, Danielle Miotto, Linda Kim, Calvin Sjaarda, Liset Maldonado-Alvarez & Henryk Fukś. (2017). Active macromolecules of honey form colloidal particles essential for honey antibacterial activity and hydrogen peroxide production. Scientific Reports | 7: 7637 | DOI:10.1038/s41598-017-08072-0
- Segal AW, Abo A. (1993). The biochemical basis of the NADPH oxidase of phagocytes. Trends Biochem Sci. 1993 Feb;18(2):43-7.