Hypothiocyanite

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| ImageFile = {{chem2|[OSCN]-}}

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| IUPACName = Oxido thiocyanate

| OtherNames = Cyanosulfoxylate

| Section1 = {{Chembox Identifiers

| CASNo = 63296-34-4

| PubChem = 124984

| UNII = N84CZ7T0OY

| DrugBank = DB15309

| SMILES = C(#N)S[O-]

| InChI = 1S/CHNOS/c2-1-4-3/h3H/p-1

| InChIKey = ZCZCOXLLICTZAH-UHFFFAOYSA-M

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| Section2 = {{Chembox Properties

| O = 1 | S = 1 | C = 1 | N = 1

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| Section3 = {{Chembox Hazards

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Hypothiocyanite is the anion [OSCN]⁻ and the conjugate base of hypothiocyanous acid (HOSCN). It is an organic compound part of the thiocyanates as it contains the functional group SCN. It is formed when an oxygen is singly bonded to the thiocyanate group. Hypothiocyanous acid is a fairly weak acid; its acid dissociation constant (pK_a) is 5.3.

Hypothiocyanite is formed by peroxidase{{cite journal |vauthors=Furtmüller PG, Zederbauer M, Jantschko W, Helm J, Bogner M, Jakopitsch C, Obinger C | title = Active site structure and catalytic mechanisms of human peroxidases | journal = Arch. Biochem. Biophys. | volume = 445 | issue = 2 | pages = 199–213 |date=January 2006 | pmid = 16288970 | doi = 10.1016/j.abb.2005.09.017 }} catalysis of hydrogen peroxide and thiocyanate:

: H₂O₂ + SCN⁻ → OSCN⁻ + H₂O

As a bactericide

Hypothiocyanite occurs naturally in the antimicrobial immune system of the human respiratory tract{{cite journal | author = Al Obaidi AH | title = Role of airway lactoperoxidase in scavenging of hydrogen peroxide damage in asthma | journal = Ann Thorac Med | volume = 2 | issue = 3 | pages = 107–10 |date=July 2007 | pmid = 19727356 | pmc = 2732085 | doi = 10.4103/1817-1737.33698 | doi-access = free }} in a redox reaction catalyzed by the enzyme lactoperoxidase.{{cite journal |vauthors=Moskwa P, Lorentzen D, Excoffon KJ, Zabner J, McCray PB, Nauseef WM, Dupuy C, Bánfi B | title = A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis | journal = Am. J. Respir. Crit. Care Med. | volume = 175 | issue = 2 | pages = 174–83 |date=January 2007 | pmid = 17082494 | pmc = 2720149 | doi = 10.1164/rccm.200607-1029OC }} It has been researched extensively for its capabilities as an alternative antibiotic as it is harmless to human body cells while being cytotoxic to bacteria.{{cite journal |vauthors=Carlsson J, Edlund MB, Hänström L | title = Bactericidal and cytotoxic effects of hypothiocyanite-hydrogen peroxide mixtures | journal = Infect. Immun. | volume = 44 | issue = 3 | pages = 581–6 |date=June 1984 | pmid = 6724690 | pmc = 263633 | doi = 10.1128/IAI.44.3.581-586.1984}} The exact processes for making hypothiocyanite have been patented as such an effective antimicrobial has many commercial applications.{{cite journal |vauthors=Mansson-Rahemtulla B, Pruitt KM, Tenovuo J, Le TM | title = A mouthrinse which optimizes in vivo generation of hypothiocyanite | journal = J. Dent. Res. | volume = 62 | issue = 10 | pages = 1062–6 |date=October 1983 | pmid = 6578235 | doi = 10.1177/00220345830620101101| s2cid = 19490884 }}

= Mechanism of action =

Lactoperoxidase-catalysed reactions yield short-lived intermediary oxidation products of SCN⁻, providing antibacterial activity.{{cite journal |vauthors=Pruitt KM, Tenovuo J, Andrews RW, McKane T | title = Lactoperoxidase-catalyzed oxidation of thiocyanate: polarographic study of the oxidation products | journal = Biochemistry | volume = 21 | issue = 3 | pages = 562–7 |date=February 1982 | pmid = 7066307 | doi = 10.1021/bi00532a023}}

The major intermediary oxidation product is hypothiocyanite OSCN⁻, which is produced in an amount of about 1 mole per mole of hydrogen peroxide. At the pH optimum of 5.3, the OSCN⁻ is in equilibrium with HOSCN. The uncharged HOSCN is considered to be the greater bactericidal of the two forms.{{cite journal |vauthors=Thomas EL, Pera KA, Smith KW, Chwang AK | title = Inhibition of Streptococcus mutans by the lactoperoxidase antimicrobial system | journal = Infect. Immun. | volume = 39 | issue = 2 | pages = 767–78 |date=February 1983 | pmid = 6832819 | pmc = 348016 | doi = 10.1128/IAI.39.2.767-778.1983}} At pH 7, it was evaluated that HOSCN represents 2% compare to OSCN⁻ 98%.{{cite journal | author = Thomas EL | title = Lactoperoxidase-catalyzed oxidation of thiocyanate: equilibria between oxidized forms of thiocyanate | journal = Biochemistry | volume = 20 | issue = 11 | pages = 3273–80 |date=May 1981 | pmid = 7248282 | doi = 10.1021/bi00514a045}}

The action of OSCN⁻ against bacteria is reported to be caused by sulfhydryl (SH) oxidation.{{cite journal |vauthors=Thomas EL, Aune TM | title = Lactoperoxidase, peroxide, thiocyanate antimicrobial system: correlation of sulfhydryl oxidation with antimicrobial action | journal = Infect. Immun. | volume = 20 | issue = 2 | pages = 456–63 |date=May 1978 | pmid = 352945 | pmc = 421877 | doi = 10.1128/IAI.20.2.456-463.1978}}

The oxidation of -SH groups in the bacterial cytoplasmic membrane results in loss of the ability to transport glucose and also in leaking of potassium ions, amino acids and peptide.

OSCN⁻ has also been identified as an antimicrobial agent in milk, saliva,{{cite journal | author = Tenovuo J | title = Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety | journal = Oral Dis | volume = 8 | issue = 1 | pages = 23–9 |date=January 2002 | pmid = 11936452 | doi = 10.1034/j.1601-0825.2002.1o781.x}} tears, and mucus.

OSCN⁻ is considered as a safe product as it is not mutagenic.{{cite journal |vauthors=White WE, Pruitt KM, Mansson-Rahemtulla B | title = Peroxidase-Thiocyanate-Peroxide Antibacterial System Does Not Damage DNA | journal = Antimicrob. Agents Chemother. | volume = 23 | issue = 2 | pages = 267–72 |date=February 1983 | pmid = 6340603 | pmc = 186035 | doi = 10.1128/aac.23.2.267}}

= Relation to cystic fibrosis =

Initially, this particular lactoperoxidase-catalyzed compound was originally discovered while viewing the specific environment of cystic fibrosis patients' weakened respiratory immune system against bacterial infection.{{cite journal |vauthors=Gattas MV, Forteza R, Fragoso MA, Fregien N, Salas P, Salathe M, Conner GE | title = Oxidative epithelial host defense is regulated by infectious and inflammatory stimuli | journal = Free Radic. Biol. Med. | volume = 47 | issue = 10 | pages = 1450–8 |date=November 2009 | pmid = 19703552 | pmc = 2767478 | doi = 10.1016/j.freeradbiomed.2009.08.017 }}

Symptoms of cystic fibrosis include an inability to secrete sufficient quantities of SCN⁻ which results in a shortage of necessary hypothiocyanite, resulting in increasing mucous viscosity, inflammation and bacterial infection in the respiratory tract.

Lactoferrin with hypothiocyanite has been granted orphan drug status by the EMEA{{cite web| url =http://www.ema.europa.eu/pdfs/human/comp/opinion/39298409en.pdf| title =Public summary of positive opinion for orphan designation of hypothiocyanite / lactoferrin for the treatment of cystic fibrosis| date =2009-09-07| work =Pre-authorisation Evaluation of Medicines for Human Use| publisher =European Medicines Agency| archive-url =https://web.archive.org/web/20100530100046/http://www.ema.europa.eu/pdfs/human/comp/opinion/39298409en.pdf| archive-date =2010-05-30| access-date =2010-01-23| url-status =dead}} and the FDA.{{cite web| url =http://www.bioalaxia.eu/content/meveol-orphan-drug-status-granted-fda-treatment-cystic-fibrosis| title =Meveol: orphan drug status granted by the FDA for the treatment of cystic fibrosis| date =2009-11-05| publisher =United States Food and Drug Administration| archive-url =https://web.archive.org/web/20091224145219/http://www.bioalaxia.eu/content/meveol-orphan-drug-status-granted-fda-treatment-cystic-fibrosis| archive-date =2009-12-24| access-date =2010-01-23| url-status =dead}}

Naturally, the discovery correlated with studies exploring different methods seeking to further gain alternative antibiotics, understanding that most older antibiotics are decreasing in effectiveness against bacteria with antibiotic resistance.{{medical citation needed|date=December 2021}}

OSCN⁻, which is not an antibiotic, has proved efficacy on superbugs including MRSA reference strains, BCC, Mucoid PA{{medical citation needed|date=December 2021}}

Schema of LPO/SCN⁻/H₂O₂ in human lung:

File:Schemaduoxlpo_en.jpg

= Efficacy range =

Non exhaustive list of microorganisms.

Bacteria (Gram-positive and -negative)

Viruses{{cite journal | vauthors = Mikola H, Waris M, Tenovuo J | date = Mar 1995 | title = Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite | journal = Antiviral Res. | volume = 26 | issue = 2| pages = 161–71 | doi=10.1016/0166-3542(94)00073-h| pmid = 7605114 }}

Yeasts and moulds

Hypothiocyanite

As a bactericide

= Mechanism of action =

= Relation to cystic fibrosis =

= Efficacy range =

See also

References

Further reading