Hypochlorous acid

Hypochlorous acid is an inorganic compound with the chemical formula, also written as HClO, HOCl, or ClHO. Its structure is. It is an acid that forms when chlorine dissolves in water, and itself partially dissociates, forming a hypochlorite anion,. HClO and are oxidizers, and the primary disinfection agents of chlorine solutions. HClO cannot be isolated from these solutions due to rapid equilibration with its precursor, chlorine.
Because of its strong antimicrobial properties, the related compounds sodium hypochlorite and calcium hypochlorite are ingredients in many commercial bleaches, deodorants, and disinfectants. The white blood cells of mammals, such as humans, also contain hypochlorous acid as a tool against foreign bodies. In living organisms, HOCl is generated by the reaction of hydrogen peroxide with chloride ions under the catalysis of the heme enzyme myeloperoxidase.
Like many other disinfectants, hypochlorous acid solutions will destroy pathogens, such as COVID-19, adsorbed on surfaces. In low concentrations, such solutions can serve to disinfect open wounds.

History

Hypochlorous acid was discovered in 1834 by the French chemist Antoine Jérôme Balard by adding a dilute suspension of mercury oxide in water to a flask of chlorine gas. He also named the acid and its compounds.
Hypochlorous acid is relatively easy to make, but it is difficult to maintain a stable solution. It is not until recent years that scientists have been able to cost-effectively produce and maintain hypochlorous acid water for stable commercial use.

Uses

In organic synthesis, HClO converts alkenes to chlorohydrins.
In biology, hypochlorous acid is generated in activated neutrophils by myeloperoxidase-mediated peroxidation of chloride ions, and contributes to the destruction of bacteria and other microbes.
In medicine, hypochlorous acid water has been used as a disinfectant and sanitiser.
In wound care, and as of early 2016 the U.S. Food and Drug Administration has approved products whose main active ingredient is hypochlorous acid for use in treating wounds and various infections in humans and pets. It is also FDA-approved as a preservative for saline solutions.
In disinfection, it has been used in the form of liquid spray, wet wipes and aerosolised application. Recent studies have shown hypochlorous acid water to be suitable for fog and aerosolised application for disinfection chambers and suitable for disinfecting indoor settings such as offices, hospitals and healthcare clinics.
In food service and water distribution, specialized equipment to generate weak solutions of HClO from water and salt is sometimes used to generate adequate quantities of safe disinfectant to treat food preparation surfaces and water supplies. It is also commonly used in restaurants due to its non-flammable and nontoxic characteristics.
In water treatment, hypochlorous acid is the active sanitizer in hypochlorite-based products.
Similarly, in ships and yachts, marine sanitation devices use electricity to convert seawater into hypochlorous acid to disinfect macerated faecal waste before discharge into the sea.
In deodorization, hypochlorous acid has been tested to remove up to 99% of foul odours including garbage, rotten meat, toilet, stool, and urine odours.
Formation, stability and reactions

Addition of chlorine to water gives both hydrochloric acid and hypochlorous acid :
When acids are added to aqueous salts of hypochlorous acid, the resultant reaction is driven to the left, and chlorine gas is formed. Thus, the formation of stable hypochlorite bleaches is facilitated by dissolving chlorine gas into basic water solutions, such as sodium hydroxide.
The acid can also be prepared by dissolving dichlorine monoxide in water; under standard aqueous conditions, anhydrous hypochlorous acid is currently impossible to prepare due to the readily reversible equilibrium between it and its anhydride:
The presence of light or transition metal oxides of copper, nickel, or cobalt accelerates the exothermic decomposition into hydrochloric acid and oxygen:

Fundamental reactions

In aqueous solution, hypochlorous acid partially dissociates into the anion hypochlorite :
Salts of hypochlorous acid are called hypochlorites. One of the best-known hypochlorites is NaClO, the active ingredient in bleach.
HClO is a stronger oxidant than chlorine under standard conditions.
HClO reacts with HCl to form chlorine:
HClO reacts with ammonia to form monochloramine:
HClO can also react with organic amines, forming N-chloroamines.
Hypochlorous acid exists in equilibrium with its anhydride, dichlorine monoxide.

Reactivity of HClO with biomolecules

Hypochlorous acid reacts with a wide variety of biomolecules, including DNA, RNA, fatty acid groups, cholesterol and proteins.

Reaction with protein sulfhydryl groups

Knox et al. first noted that HClO is a sulfhydryl inhibitor that, in sufficient quantity, could completely inactivate proteins containing sulfhydryl groups. This is because HClO oxidises sulfhydryl groups, leading to the formation of disulfide bonds that can result in crosslinking of proteins. The HClO mechanism of sulfhydryl oxidation is similar to that of monochloramine, and may only be bacteriostatic, because once the residual chlorine is dissipated, some sulfhydryl function can be restored. One sulfhydryl-containing amino acid can scavenge up to four molecules of HClO. Consistent with this, it has been proposed that sulfhydryl groups of sulfur-containing amino acids can be oxidized a total of three times by three HClO molecules, with the fourth reacting with the α-amino group. The first reaction yields sulfenic acid then sulfinic acid and finally. Sulfenic acids form disulfides with another protein sulfhydryl group, causing cross-linking and aggregation of proteins. Sulfinic acid and derivatives are produced only at high molar excesses of HClO, and disulfides are formed primarily at bacteriocidal levels. Disulfide bonds can also be oxidized by HClO to sulfinic acid. Because the oxidation of sulfhydryls and disulfides evolves hydrochloric acid, this process results in the depletion HClO.

Reaction with protein amino groups

Hypochlorous acid reacts readily with amino acids that have amino group side-chains, with the chlorine from HClO displacing a hydrogen, resulting in an organic chloramine. Chlorinated amino acids rapidly decompose, but protein chloramines are longer-lived and retain some oxidative capacity. Thomas et al. concluded from their results that most organic chloramines decayed by internal rearrangement and that fewer available NH2 groups promoted attack on the peptide bond, resulting in cleavage of the protein. McKenna and Davies found that 10 mM or greater HClO is necessary to fragment proteins in vivo. Consistent with these results, it was later proposed that the chloramine undergoes a molecular rearrangement, releasing HCl and ammonia to form an aldehyde. The aldehyde group can further react with another amino group to form a Schiff base, causing cross-linking and aggregation of proteins.

Reaction with DNA and nucleotides

Hypochlorous acid reacts slowly with DNA and RNA as well as all nucleotides in vitro. GMP is the most reactive because HClO reacts with both the heterocyclic NH group and the amino group. In similar manner, TMP with only a heterocyclic NH group that is reactive with HClO is the second-most reactive. AMP and CMP, which have only a slowly reactive amino group, are less reactive with HClO. UMP has been reported to be reactive only at a very slow rate. The heterocyclic NH groups are more reactive than amino groups, and their secondary chloramines are able to donate the chlorine. These reactions likely interfere with DNA base pairing, and, consistent with this, Prütz has reported a decrease in viscosity of DNA exposed to HClO similar to that seen with heat denaturation. The sugar moieties are nonreactive and the DNA backbone is not broken. NADH can react with chlorinated TMP and UMP as well as HClO. This reaction can regenerate UMP and TMP and results in the 5-hydroxy derivative of NADH. The reaction with TMP or UMP is slowly reversible to regenerate HClO. A second slower reaction that results in cleavage of the pyridine ring occurs when excess HClO is present. is inert to HClO.

Reaction with lipids

Hypochlorous acid reacts with unsaturated bonds in lipids, but not saturated bonds, and the hypochlorite| ion does not participate in this reaction. This reaction occurs by hydrolysis with addition of chlorine to one of the carbons and a hydroxyl to the other. The resulting compound is a chlorohydrin. The polar chlorine disrupts lipid bilayers and could increase permeability. When chlorohydrin formation occurs in lipid bilayers of red blood cells, increased permeability occurs. Disruption could occur if enough chlorohydrin is formed. The addition of preformed chlorohydrin to red blood cells can affect permeability as well. Cholesterol chlorohydrin have also been observed, but do not greatly affect permeability, and it is believed that chlorine| is responsible for this reaction. Hypochlorous acid also reacts with a subclass of glycerophospholipids called plasmalogens, yielding chlorinated fatty aldehydes which are capable of protein modification and may play a role in inflammatory processes such as platelet aggregation and the formation of neutrophil extracellular traps.

Mode of disinfectant action

E. coli exposed to hypochlorous acid lose viability in less than 0.1 seconds due to inactivation of many vital systems. Hypochlorous acid has a reported of 0.0104–0.156 ppm and 2.6 ppm caused 100% growth inhibition in 5 minutes. However, the concentration required for bactericidal activity is also highly dependent on bacterial concentration.