Chemistry:Hypothiocyanite

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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 (pKa) is 5.3. Hypothiocyanite is formed by peroxidase[1] 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[2] in a redox reaction catalyzed by the enzyme lactoperoxidase.[3] 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.[4] The exact processes for making hypothiocyanite have been patented as such an effective antimicrobial has many commercial applications.[5]

Mechanism of action

Lactoperoxidase-catalysed reactions yield short-lived intermediary oxidation products of SCN−, providing antibacterial activity.[6]

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.[7] At pH 7, it was evaluated that HOSCN represents 2% compare to OSCN− 98%.[8]

The action of OSCN− against bacteria is reported to be caused by sulfhydryl (SH) oxidation.[9]

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,[10] tears, and mucus.

OSCN− is considered as a safe product as it is not mutagenic.[11]

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.[12]

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[13] and the FDA.[14]

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.

OSCN−, which is not an antibiotic, has proved efficacy on superbugs including MRSA reference strains, BCC, Mucoid PA

Schema of LPO/SCN−/H2O2 in human lung[clarification needed]

Efficacy range

Non exhaustive list of microorganisms.

Bacteria (Gram-positive and -negative)

Viruses[15]

Yeasts and moulds

See also

References

  1. ↑ "Active site structure and catalytic mechanisms of human peroxidases". Arch. Biochem. Biophys. 445 (2): 199–213. January 2006. doi:10.1016/j.abb.2005.09.017. PMID 16288970. 
  2. ↑ Al Obaidi AH (July 2007). "Role of airway lactoperoxidase in scavenging of hydrogen peroxide damage in asthma". Ann Thorac Med 2 (3): 107–10. doi:10.4103/1817-1737.33698. PMID 19727356. 
  3. ↑ "A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis". Am. J. Respir. Crit. Care Med. 175 (2): 174–83. January 2007. doi:10.1164/rccm.200607-1029OC. PMID 17082494. 
  4. ↑ "Bactericidal and cytotoxic effects of hypothiocyanite-hydrogen peroxide mixtures". Infect. Immun. 44 (3): 581–6. June 1984. doi:10.1128/IAI.44.3.581-586.1984. PMID 6724690. 
  5. ↑ "A mouthrinse which optimizes in vivo generation of hypothiocyanite". J. Dent. Res. 62 (10): 1062–6. October 1983. doi:10.1177/00220345830620101101. PMID 6578235. 
  6. ↑ "Lactoperoxidase-catalyzed oxidation of thiocyanate: polarographic study of the oxidation products". Biochemistry 21 (3): 562–7. February 1982. doi:10.1021/bi00532a023. PMID 7066307. 
  7. ↑ "Inhibition of Streptococcus mutans by the lactoperoxidase antimicrobial system". Infect. Immun. 39 (2): 767–78. February 1983. doi:10.1128/IAI.39.2.767-778.1983. PMID 6832819. 
  8. ↑ Thomas EL (May 1981). "Lactoperoxidase-catalyzed oxidation of thiocyanate: equilibria between oxidized forms of thiocyanate". Biochemistry 20 (11): 3273–80. doi:10.1021/bi00514a045. PMID 7248282. 
  9. ↑ "Lactoperoxidase, peroxide, thiocyanate antimicrobial system: correlation of sulfhydryl oxidation with antimicrobial action". Infect. Immun. 20 (2): 456–63. May 1978. doi:10.1128/IAI.20.2.456-463.1978. PMID 352945. 
  10. ↑ Tenovuo J (January 2002). "Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety". Oral Dis 8 (1): 23–9. doi:10.1034/j.1601-0825.2002.1o781.x. PMID 11936452. 
  11. ↑ "Peroxidase-Thiocyanate-Peroxide Antibacterial System Does Not Damage DNA". Antimicrob. Agents Chemother. 23 (2): 267–72. February 1983. doi:10.1128/aac.23.2.267. PMID 6340603. 
  12. ↑ "Oxidative epithelial host defense is regulated by infectious and inflammatory stimuli". Free Radic. Biol. Med. 47 (10): 1450–8. November 2009. doi:10.1016/j.freeradbiomed.2009.08.017. PMID 19703552. 
  13. ↑ "Public summary of positive opinion for orphan designation of hypothiocyanite / lactoferrin for the treatment of cystic fibrosis". Pre-authorisation Evaluation of Medicines for Human Use. European Medicines Agency. 2009-09-07. http://www.ema.europa.eu/pdfs/human/comp/opinion/39298409en.pdf. 
  14. ↑ "Meveol: orphan drug status granted by the FDA for the treatment of cystic fibrosis". United States Food and Drug Administration. 2009-11-05. http://www.bioalaxia.eu/content/meveol-orphan-drug-status-granted-fda-treatment-cystic-fibrosis. 
  15. ↑ "Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite". Antiviral Res. 26 (2): 161–71. Mar 1995. doi:10.1016/0166-3542(94)00073-h. PMID 7605114. 

Further reading



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