View source for Zinc pyrithione

{{Short description|Chemical compound}}
{{Use dmy dates|date=March 2023}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Chembox
| Watchedfields = changed
| verifiedrevid = 402542377
| ImageFile = Zink-Pyrithion.svg
| ImageSize =
| ImageFile1 = Zinc-pyrithione-dimer-3D-balls.png
| ImageSize1 = 250
| ImageCaption1 = Zinc pyrithione dimer
| IUPACName = bis(2-pyridylthio)zinc 1,1'-dioxide
| OtherNames = ZnP, Pyrithione Zinc, Zinc OMADINE, ZnPT
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 21513957
| ChEMBL = 1200471
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = R953O2RHZ5
| InChI = 1/C5H5NOS.Zn/c7-6-4-2-1-3-5(6)8;/h1-4,7H;/q;+2
| InChIKey = YUYSACQNSLQTMI-UHFFFAOYAS
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 13463-41-7
| PubChem = 3005837<!--using CID of USAN generic compound; 26041 appears to be formulation or vendor-specific? -->
| SMILES = c1cc[n+]2c(c1)S[Zn-2]3(O2)O[n+]4ccccc4S3
| SMILES_Comment = monomer
| SMILES1 = [O+]01[n+]2ccccc2S[Zn-3]03(O[n+]4ccccc4S3)[O+]5[n+]6ccccc6S[Zn-3]157O[n+]8ccccc8S7
| SMILES1_Comment = dimer
}}
|Section2={{Chembox Properties
| Formula = C<sub>10</sub>H<sub>8</sub>N<sub>2</sub>O<sub>2</sub>S<sub>2</sub>Zn
| MolarMass = 317.70 g/mol
| Appearance = colourless solid
| Density =
| MeltingPtC = 240
| MeltingPt_notes = (decomposition)<ref name="Römpp">{{RömppOnline|ID=RD-26-00395|Name=Zink-Pyrithion|Datum=5 November 2020}}</ref>
| BoilingPt = decomposes
| Solubility = 8&nbsp;ppm (pH 7)
  }}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = D11
| ATCCode_suffix = AX12
}}
|Section7={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
 }}
}}
<!--{{Drugbox
| verifiedrevid = 470636767
| IUPAC_name =
| image = Zinc pyrithione.png
| width = 208px
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 13463-41-7
| ATC_prefix = D11
| ATC_suffix = AX12
| ATC_supplemental =
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C5H5NOS.Zn/c7-6-4-2-1-3-5(6)8;/h1-4,7H;/q;+2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YUYSACQNSLQTMI-UHFFFAOYSA-N
| PubChem =26041 | C=10 | H=8 | N=2 | O=2 | S=2 | Zn=1
| molecular_weight = 317.705
| bioavailability =
| metabolism =
| elimination_half-life=
| excretion =
| Pregnancy_category =
| Legal_status = [[Over-the-counter drug|OTC]] (US)
| routes_of_administration = Topical
}}-->
'''Zinc pyrithione''' (or '''pyrithione zinc''') is a [[coordination compound|coordination complex]] of [[zinc]]. It has [[Fungistatics|fungistatic]] (inhibiting the division of fungal cells) and [[bacteriostatic]] (inhibiting bacterial cell division) properties and is used in the treatment of [[seborrhoeic dermatitis]]<ref name="MD">{{cite web |title=Pyrithione Zinc |work=Martindale: The Complete Drug Reference |publisher=Pharmaceutical Press |date=23 September 2011 |access-date=28 March 2014 | veditors = Brayfield A |url=http://www.medicinescomplete.com/mc/martindale/current/1633-s.htm |archive-date=26 March 2020 |archive-url=https://web.archive.org/web/20200326121901/http://www.medicinescomplete.com/mc/martindale/current/1633-s.htm |url-status=live }}</ref> and [[dandruff]].

== Structure of the compound ==
The [[pyrithione]] ligands, which are formally [[Anion|monoanions]], are [[Chelation|chelated]] to Zn<sup>2+</sup> via [[oxygen]] and [[sulfur]] centers. In the crystalline state, zinc pyrithione exists as a centrosymmetric dimer (see figure), where each zinc is bonded to two sulfur and three oxygen centers.<ref>{{cite journal | vauthors = Barnett BL, Kretschmar HC, Hartman FA |title=Structural characterization of bis(N-oxopyridine-2-thionato)zinc(II) |journal=[[Inorg. Chem.]] |year=1977 |volume=16 |issue=8 |pages=1834–8 |doi=10.1021/ic50174a002 }}</ref>  In solution, however, the dimers dissociate via scission of one Zn-O [[Chemical bond|bond]].{{citation needed|date=December 2022}}

This compound was first described in the 1930s.<ref>{{cite web |url=http://www.cas.astate.edu/draganjac/pyrithionezinc.html |title=Pyrithione zinc |access-date=24 August 2007 |url-status=dead |archive-url=https://web.archive.org/web/20070621193113/http://www.cas.astate.edu/draganjac/pyrithionezinc.html |archive-date=21 June 2007 |website=www.cas.astate.edu | vauthors = Draganjac M |publisher=Arkansas State University}}</ref>

Pyrithione is the [[conjugate base]] derived from 2-mercaptopyridine-''N''-oxide (CAS# 1121-31-9), a derivative of [[pyridine-N-oxide|pyridine-''N''-oxide]].{{citation needed|date=December 2022}}

== Uses ==

=== Medicine ===
Zinc pyrithione can be used to treat [[dandruff]] and [[seborrhoeic dermatitis]].<ref>{{cite journal | vauthors = Marks R, Pearse AD, Walker AP | title = The effects of a shampoo containing zinc pyrithione on the control of dandruff | journal = The British Journal of Dermatology | volume = 112 | issue = 4 | pages = 415–422 | date = April 1985 | pmid = 3158327 | doi = 10.1111/j.1365-2133.1985.tb02314.x  | s2cid = 23368244 }}</ref><ref>{{cite journal | vauthors = Piérard-Franchimont C, Goffin V, Decroix J, Piérard GE | title = A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis | journal = Skin Pharmacology and Applied Skin Physiology | volume = 15 | issue = 6 | pages = 434–441 | date = November 2002 | pmid = 12476017 | doi = 10.1159/000066452 | s2cid = 23162407 }}</ref><ref>{{cite journal | vauthors = Ive FA | title = An overview of experience with ketoconazole shampoo | journal = The British Journal of Clinical Practice | volume = 45 | issue = 4 | pages = 279–284 | date = 1991 | pmid = 1839767 }}</ref> It also has antibacterial properties and is effective against many [[pathogen]]s from the ''[[Streptococcus]]'' and ''[[Staphylococcus]]'' genera.<ref name="American Chem Soc">{{Cite web |title=Zinc pyrithione |url=https://www.acs.org/content/acs/en/molecule-of-the-week/archive/z/zinc-pyrithione.html |access-date=14 May 2021 | work = Molecule of the Week Archive |publisher = American Chemical Society |language=en |archive-date=1 March 2021 |archive-url=https://web.archive.org/web/20210301232215/https://www.acs.org/content/acs/en/molecule-of-the-week/archive/z/zinc-pyrithione.html |url-status=live }}</ref> Its other medical applications include treatments of [[psoriasis]], [[eczema]], [[ringworm]], [[fungus]], [[athletes foot]], [[dry skin]], [[atopic dermatitis]], [[tinea versicolor]],<ref>{{cite journal | vauthors = Faergemann J | title = Management of seborrheic dermatitis and pityriasis versicolor | journal = American Journal of Clinical Dermatology | volume = 1 | issue = 2 | pages = 75–80 | date = 2000 | pmid = 11702314 | doi = 10.2165/00128071-200001020-00001 | s2cid = 43516330 }}</ref><ref name="American Chem Soc" /> and [[vitiligo]].{{medical citation needed|date=September 2020}}

=== Paint ===
Because of its low [[solubility]] in [[water]] (8&nbsp;ppm at neutral pH), zinc pyrithione is suitable for use in outdoor [[paint]]s and other products that protect against [[mildew]] and [[algae]]. It is an [[algaecide]]. It is chemically incompatible with paints relying on metal carboxylate curing agents. When it is used in latex paints with water containing much [[iron]], a sequestering agent that preferentially binds the iron ions is needed. It is decomposed by [[ultraviolet]] light slowly, providing years of protection in direct sunlight.{{citation needed|date=December 2022}}

=== Sponges ===
Zinc pyrithione is an [[antibacterial]] treatment for household [[Sponge (material)|sponge]]s, as used by the [[3M Corporation]].<ref>{{Cite web |url=http://legalminds.lp.findlaw.com/list/epa-pest/msg01049.html |title=Notice of Filing a Pesticide Petition to Establish<!-- Bot generated title --> |access-date=3 December 2007 |archive-date=18 November 2017 |archive-url=https://web.archive.org/web/20171118225022/http://lp.findlaw.com/ |url-status=live }}</ref><ref>{{cite journal | vauthors = Schroeder JW, Corn S, Battiste J, Stepanova N, Weiss C, Thiele J | title = In-situ immobilization of pyrithione in cellulose sponge for durable antimicrobial effect. | journal = Cellulose | date = December 2023 | volume = 30 | issue = 18 | pages = 11753–11765 | doi = 10.1007/s10570-023-05595-w
 }}</ref>

=== Clothing ===
A process to apply zinc pyrithione to cotton with washable results was patented in the United States in 1984.<ref>{{cite patent |country=US |number=US4443222A |status= |title= |pubdate= |gdate= 17 April 1984 |fdate= |pridate=  |inventor= Morris CE, Welch CM |assign1=The United States of America as represented by the Secretary of Agriculture}}</ref> Zinc pyrithione is used to prevent microbe growth in [[polyester]].<ref>{{cite web |title=Zptech, Zinc Odor Control for Textiles |url=https://www.microban.com/odor-control/technologies/zptech |website=microban.com |publisher=Microban International |archive-url=https://web.archive.org/web/20230702013210/https://www.microban.com/odor-control/technologies/zptech |archive-date=2023-07-02 |access-date=2023-09-23}}</ref> Textiles with applied zinc pyrithione protect against odor-causing microorganisms. Export of antimicrobial textiles reached US$497.4 million in 2015.<ref>{{cite journal | vauthors = Jain AK, Tesema AF | title = Development of antimicrobial textiles using zinc pyrithione. | journal = Research Journal of Textile and Apparel. | date = September 2017 | volume = 21 | issue = 3 | pages= 188–202 | doi = 10.1108/RJTA-06-2017-0031 }}</ref>

== Mechanism of action ==

=== Antibacterial effect ===
Zinc pyrithione is known to exhibit antibacterial activity by disrupting cell membrane integrity and essential metabolic functions in bacteria.<ref>{{cite journal | vauthors = Blanchard C, Brooks L, Ebsworth-Mojica K, Didione L, Wucher B, Dewhurst S, Krysan D, Dunman PM, Wozniak RA | title = Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment | journal = mSphere | volume = 1 | issue = 5 | date = 2016-10-26 | pmid = 27642637 | pmc = 5023846 | doi = 10.1128/mSphere.00194-16 | veditors = Fey PD }}</ref> 

=== Antifungal effect ===
Its antifungal effect is thought to derive from its ability to disrupt [[cell membrane|membrane]] transport by blocking the [[proton pump]] that energizes the transport mechanism.<ref>{{cite journal | vauthors = Chandler CJ, Segel IH | title = Mechanism of the antimicrobial action of pyrithione: effects on membrane transport, ATP levels, and protein synthesis | journal = Antimicrobial Agents and Chemotherapy | volume = 14 | issue = 1 | pages = 60–68 | date = July 1978 | pmid = 28693 | pmc = 352405 | doi = 10.1128/aac.14.1.60 }}</ref> A study from 2011 showed that antifungal effects of zinc pyrithione work by [[copper toxicity]] mechanism that targets critical [[Iron-sulfur protein|iron–sulphur proteins]].<ref>{{cite journal | vauthors = Reeder NL, Xu J, Youngquist RS, Schwartz JR, Rust RC, Saunders CW | title = The antifungal mechanism of action of zinc pyrithione | journal = The British Journal of Dermatology | volume = 165 | issue = Suppl 2 | pages = 9–12 | date = October 2011 | pmid = 21919897 | doi = 10.1111/j.1365-2133.2011.10571.x }}</ref>

== Health effects ==
Zinc pyrithione is approved for [[Over-the-counter drug|over-the-counter]] topical use in the United States as a treatment for [[dandruff]] and is the active ingredient in several anti-dandruff shampoos and body wash gels. In its industrial forms and strengths, it may be harmful by contact or ingestion. Zinc pyrithione can in the laboratory setting trigger a variety of responses, such as DNA damage in skin cells.<ref>Leading references: {{cite journal | vauthors = Lamore SD, Cabello CM, Wondrak GT | title = The topical antimicrobial zinc pyrithione is a heat shock response inducer that causes DNA damage and PARP-dependent energy crisis in human skin cells | journal = Cell Stress & Chaperones | volume = 15 | issue = 3 | pages = 309–322 | date = May 2010 | pmid = 19809895 | pmc = 2866994 | doi = 10.1007/s12192-009-0145-6 }}</ref>

== Legal status ==

=== European Union ===
Use of zinc pyrithione is prohibited within cosmetic products in the [[European Union]] since December 2021.<ref name="EU Commission Regulation-2021">{{Citation |title=Commission Regulation (EU) 2021/1902 of 29&nbsp;October 2021 amending Annexes II, III and V to Regulation (EC) No&nbsp;1223/2009 of the European Parliament and of the Council as regards the use in cosmetic products of certain substances classified as carcinogenic, mutagenic or toxic for reproduction (Text with EEA relevance) |date=3 November 2021 |url=http://data.europa.eu/eli/reg/2021/1902/oj/eng |issue=32021R1902 |language=en |access-date=9 August 2022 |archive-date=24 February 2024 |archive-url=https://web.archive.org/web/20240224043427/https://eur-lex.europa.eu/eli/reg/2021/1902/oj/eng |url-status=live }}</ref> The substance was considered safe for use in rinse-off and leave-in products of different tested concentrations, but due to potential environmental toxicity consideration of the use of zinc pyrithione was made against potential alternative substance ingredients. Due to no industry submission to the regulators supporting the continued use of zinc pyrithione and/or an absence of indications that there were no suitable alternatives to the substance: the use of zinc pyrithione became automatically prohibited within cosmetic products as an intended ingredient. This was as a consequence of zinc pyrithione addition to the Cosmetic Product Regulation (EC) No 1223/2009 Annex II list.<ref name="EU Commission Regulation-2021" />

=== United States ===
Zinc pyrithione concentration of up to 2% is allowed for products when they are formulated to be applied and then washed off after brief exposure. Alternatively, up to 0.25 percent when formulated to be left on the skin or scalp <ref>{{Cite web |title=21 CFR 358.710 -- Active ingredients for the control of dandruff, seborrheic dermatitis, or psoriasis. |url=https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-358/subpart-H/section-358.710 |access-date=2024-08-18 |website=www.ecfr.gov |language=en}}</ref>

== Environmental concerns ==
A large Swedish study shows that it is broken down in [[Water treatment|wastewater plants]] and does not release into waterways.<ref>{{Cite web |title=Results from the Swedish Screening Programme 2006 Subreport 3: Zinc pyrithione and Irgarol 1051 |url=https://www.ivl.se/download/18.343dc99d14e8bb0f58b7524/1445515665956/B1764.pdf |date=September 2007 |website=ivl.se |publisher={{Interlanguage link |Swedish Environmental Research Institute |sv |IVL Svenska Miljöinstitutet}} |archive-url=https://web.archive.org/web/20210526185320/https://www.ivl.se/download/18.343dc99d14e8bb0f58b7524/1445515665956/B1764.pdf |archive-date=26 May 2021 |access-date=5 March 2023 }}</ref> A Danish study shows that it biodegrades quickly, but that a risk of continuous leaching from boat paint may cause environmental toxicity.<ref>{{Cite web |title=Ecotoxocicological assessment of antifouling biocides and non-biocidal antifouling paints |url=http://www2.mst.dk/common/Udgivramme/Frame.asp?http://www2.mst.dk/udgiv/publications/2000/87-7944-084-3/html/kap04_eng.htm |archive-url=https://archive.today/20120525185735/http://www2.mst.dk/common/Udgivramme/Frame.asp?http://www2.mst.dk/udgiv/publications/2000/87-7944-084-3/html/kap04_eng.htm |archive-date=25 May 2012 |access-date=5 March 2023 |website=Miljøstyrelsen - Miljøministeriet |publisher=[[Ministry of Environment (Denmark)]]}}</ref>

== See also ==
* [[Ketoconazole]], another antifungal agent used in shampoos
* [[Piroctone olamine]], another antifungal agent used in shampoos
* [[Selenium disulfide]], an active ingredient used in shampoos such as [[Selsun Blue]]

== References ==
{{reflist}}

{{Other dermatological preparations}}
{{Portal bar | Medicine}}

[[Category:Anti-acne preparations]]
[[Category:Antifungals]]
[[Category:Antiseptics]]
[[Category:Cosmetics chemicals]]
[[Category:Pyridinium compounds]]
[[Category:Thiols]]
[[Category:Zinc compounds]]