SODIUM PYRITHIONE

SODIUM PYRITHIONE

CAS No. : 3811-73-2

Synonyms:
Omadine sodium; Omadine sodium 40%; pyrithione sodium; 2-Pyridinethiol; 1-Hydroxy-2-pyridinethione sodium salt, 2-Mercaptopyridine-1-oxide sodium salt, 2-Pyridinethiol-1-oxide sodium salt, Pyrithione sodium salt; 2-mercaptopyridine-N-oxide; 1-hydroxypyridine-2-thione; 2-pyridinethiol-1-oxide (CAS No. 1121-31-9); 1-hydroxy-2(1H)-pyridinethione (CAS No. 1121-30-8); NaPT; Sodi; UT900000; SODIUM OMADINE; thione(reagent); Sodium pyrithion; SODIUM PYRITHIONE; PYRITHIONE SODIUM; PYRITHIONE SODIUM SALT; Sodium pyrithione(NaPT); Sodium (2-pyridylthio)-N-oxide (3811-73-2); 15922-78-8: Pyrithione sodium; 1-Hydroxy-2(1H)-pyridinethionato sodium; 1-Hydroxy-2(1H)-pyridinethione, sodium salt; AL02725; Omacide 24; Omadine sodium; SQ 3277; Sel de sodium de 1-hydroxy-2 (1H)-pyridinethione [French]; Sodium 1-hydroxypyridine-2-thione; Sodium 2-pyridinethiol-1-oxide; Sodium Omadine; Sodium pyrithione; 2(1H)-Pyridinethione, 1-hydroxy-, sodium; [ChemIDplus] 3811-73-2: 2-Pyridinethiol, 1-oxide, sodium salt; Sodium (2-pyridylthio)-N-oxide; Sodium pyrithione; (1-Hydroxy-2-pyridinethione), sodium salt; (1-Hydroxy-2-pyridinethione), sodium salt, tech.; 1-Oxo-2-pyridinethiol sodium salt; 2-Mercaptopyridine 1-oxide sodium salt; 2-Mercaptopyridine oxide sodium salt; 2-Mercaptopyridine-N-oxide sodium salt; 2-Pyridinethiol N-oxide sodium salt; 2-Pyridinethiol-1-oxide sodium salt; Omadine sodium; Sodium (2-pyridylthio)-N-oxide; Sodium 2-mercaptopyridine 1-oxide; Sodium 2-pyridinethiol 1-oxide; Sodium 2-pyridinethiol N-oxide; Sodium 2-pyridinethiolate 1-oxide; Sodium omadine (VAN); Sodium, (2-pyridinylthio)-, N-oxide; Thione (reagent); 3811-73-2; Sodium Omadine; Sodium pyrithione; Sodium (2-pyridylthio)-N-oxide; Pyrithione sodium salt; Thione (reagent); 2-Pyridinethiol-1-oxide sodium salt; 2-Mercaptopyridine N-oxide sodium salt; PYRITHIONE SODIUM; Omadine sodium; Sodium omadine (VAN); Sodium pyrithione (VAN); 2-Mercaptopyridine-N-oxide sodium salt; Sodium 2-pyridinethiol N-oxide; Sodium 2-pyridinethiol 1-oxide; Sodium 2-mercaptopyridine 1-oxide; Sodium 2-pyridinethiolate 1-oxide; UNII-6L3991491R; 1-Oxo-2-pyridinethiol sodium salt; NSC 4483; 2-Pyridinethiol N-oxide sodium salt; EINECS 223-296-5; 2-Mercaptopyridine N-oxide (sodium); 2-Mercaptopyridine oxide sodium salt; Sodium, (2-pyridinylthio)-, N-oxide; 1-Hydroxy-2-pyridinethione sodium salt; 2-Mercaptopyridine 1-oxide sodium salt; 2-Pyridinethiol, N-oxide, sodium salt; (1-Hydroxy-2-pyridinethione), sodium salt; AI3-22596; 6L3991491R; 2-Pyridinethiol, 1-oxide, sodium salt (1:1); 2-Mercaptopyridine N-oxide sodium salt anhydrous; 2-Mercaptopyridinen-oxide sodiumsalt; 2-Pyridinethiol 1-Oxide Sodium Salt; Pyridine-2-thiol 1-oxide, sodium salt; Sodium 2-sulfidopyridine 1-oxide; Sodium-2-pyridinethiol-1-oxide; MFCD01941547; Prestwick_78; 2-Mercaptopyridine-N-oxide, sodium salt; C5H4NNaOS; sodium (1-oxidopyridin-1-ium-2-yl)sulfanide; DSSTox_CID_22390; DSSTox_RID_80011; DSSTox_GSID_42390; SCHEMBL3101261; CHEMBL2364542; DTXSID3042390; 2-Mercaptopyridine n-oxide sodium; N-Hydroxypyridinethione Sodium Salt; EBD41219; STR00395; Tox21_300128; Sodium, (2-pyridylthio)-, N-oxide; AKOS000121187; sodium1-oxidopyridin-1-ium-2-thiolate; 2-Mercaptopyridine-1-oxide sodium salt; AC-1079; HY-125785A; NCGC00254107-01; CAS-3811-73-2; LS-132087; CS-0129647; M0632; M2841; Sodium, (2-pyridylthio)-, N-oxide (7CI); 2-Mercaptopyridine N-oxide sodium salt, 95%; EC 223-296-5; 2-Mercaptopyridine N-oxide sodium salt, >=96%; (1-Hydroxy-2-pyridinethione), sodium salt, tech; (1-Hydroxy-2-pyridinethione), sodium salt, tech.; 2-Mercaptopyridinen-oxide sodiumsalt 3811-73-2; W-106499; Q27265081; 2-Mercaptopyridine N-oxide sodium salt, >=96.0% (NT); Sodium pyridine-2-thiolate N-oxide, 40% aqueous solution; 2-Mercaptopyridine N-oxide sodium salt solution, ~40% in H2O, very deep brown; Sodium-2-pyridinethiol-1-oxide; 2-Mercaptopyridine-N-oxide sodium salt; 2-Pyridinethiol-1-oxide sodium salt; N-Hydroxy-2-pyridinethione sodium salt; Sodium pyrithione; PYRITHIONE SODIUM; Omadine sodium; Omadine-sodium; 15922-78-8; Omacide 24; Caswell No. 790A; 2(1H)-Pyridinethione, 1-hydroxy-, sodium salt; Pyrithione sodium [USAN]; AL02725; Sodium 2-pyridinethiol-1-oxide; Sodium 1-hydroxypyridine-2-thione; EINECS 240-062-8; EPA Pesticide Chemical Code 088004; SQ 3277; 1-Hydroxy-2(1H)-pyridinethionato sodium; pyrithione sodium; 2-Pyridinethiol; 1-Hydroxy-2-pyridinethione sodium salt, 2-Mercaptopyridine-1-oxide sodium salt, 2-Pyridinethiol-1-oxide sodium salt, Pyrithione sodium salt; 2-mercaptopyridine-N-oxide; 1-hydroxypyridine-2-thione; 2-pyridinethiol-1-oxide; 1-Hydroxy-2(1H)-pyridinethione, sodium salt; Sel de sodium de 1-hydroxy-2 (1H)-pyridinethione [French]; MFCD01941547; Pyrithione sodium (USAN); Sodium 2-sulfidopyridine 1-oxide; 2-Mercaptopyridine-N-oxide, sodium salt, 40 w/w % aqueous solution; Sodium omadine (TN); C5H4NOS.Na; Sodium Pyrithione 40% FPS; Sel de sodium de 1-hydroxy-2 (1H)-pyridinethione; SCHEMBL271923; CHEMBL2105351; DTXSID6034920; SODIUM SALT OF 1-HYDROXY 2(1H)-PYRIDINE THIONE; KKopsanop3380-34-5thione Na; AKOS015891512; 1-hydroxypyridine-2-thione sodium salt; Omadine; thione: 1-Hydroxypyridine-2-thione; N-Hydroxypyridine-2-thione; thiol: 2-Mercaptopyridine monoxide; 2-Mercaptopyridine N-oxide; 1-Hydroxy-2(1H)-pyridinethione (thione); 2-Pyridinethiol 1-oxide (thiol)

Sodium Pyrithione

Sodium pyrithione is a fungistatic and antimicrobial derivative of aspergillic acid. Although the exact mechanism of action remains to be fully elucidated, Sodium pyrithione appears to interfere with membrane transport ultimately leading to a loss of metabolic control.
Absorption
Following oral ingestion, only the Sodium pyrithione moiety is absorbed. Less than 1% of administered zinc Sodium pyrithione is absorbed from the skin [L1758]. Radioabeled Zn Sodium pyrithione administered to rats, rabbits and monkeys, either orally or via intraperitoneal injection were absorbed into circulatin to extent of 80-90% [L1758].Inhibition of fungal growth by Sodium pyrithione zinc is linked to increased copper uptake and cellular levels of copper, which is demonstrated by decreased CTR1-lacZ expression and slightly increased CUP1-lacZ expression in affected microorganisms [A32162]. The coordination complex of Sodium pyrithione zinc dissociates, and Sodium pyrithione ligand forms a CuPT complex from available extracellular copper in the target organism. Sodium pyrithione acts as an ionophore, interacting nonspecifically with the plasma membrane to shuttle copper into the cell, and facilitates copper transport across intracellular membranes [A32162]. Copper may be shuttled into the mitochondria. Copper inactivates iron-sulfur (Fe-S) cluster-containing proteins via a mechanism similar to that described for copper-induced growth inhibition in bacteria [A32162]. Decreased activity of Fe-S proteins leads to inhibition of fungal metabolism and fungal growth. Sodium pyrithione zinc has been shown to slightly increase the levels of zinc [A32162].

Sodium pyrithione (or pyrithione zinc) is a coordination complex of zinc. It has fungistatic (that is, it inhibits the division of fungal cells) and bacteriostatic (inhibits bacterial cell division) properties and is used in the treatment of seborrhoeic dermatitis.
Structure of the compound
The pyrithione ligands, which are formally monoanions, are chelated to Zn2+ via oxygen and sulfur centers. In the crystalline state, Sodium pyrithione exists as a centrosymmetric dimer (see figure), where each zinc is bonded to two sulfur and three oxygen centers.[3] In solution, however, the dimers dissociate via scission of one Zn-O bond.
This compound was first described in the 1930s.
Pyrithione is the conjugate base derived from 2-mercaptopyridine-N-oxide (CAS# 1121-31-9), a derivative of pyridine-N-oxide.

Uses
Medical
Sodium pyrithione can be used to treat dandruff and seborrhoeic dermatitis.[medical citation needed] It also has antibacterial properties and is effective against many pathogens from the Streptococcus and Staphylococcus genera.[medical citation needed] Its other medical applications include treatments of psoriasis, eczema, ringworm, fungus, athletes foot, dry skin, atopic dermatitis, tinea versicolor,[5] and vitiligo.
In paint
Due to its low solubility in water (8 ppm at neutral pH), Sodium pyrithione is suitable for use in outdoor paints and other products that provide protection against mildew and algae. It is an effective algaecide. It is chemically incompatible with paints relying on metal carboxylate curing agents. When used in latex paints with water containing high amount of iron, a sequestering agent that will preferentially bind the iron ions is needed. Its decomposition by ultraviolet light is slow, providing years of protection even against direct sunlight.
In sponges
Sodium pyrithione is also used as an antibacterial treatment for household sponges, most notably by the 3M Corporation.[6]
In clothing
A process to apply Sodium pyrithione to cotton with washable results was patented in the United States in 1984.[7] Sodium pyrithione is now used to prevent microbe growth in polyester.[8] Textiles with applied Sodium pyrithione protect against odor-causing microorganisms. Export of antimicrobial textiles reached US$497.4 million in 2015.
Mechanism of action
Its antifungal effect is thought to derive from its ability to disrupt membrane transport by blocking the proton pump that energizes the transport mechanism.
Health effects
Sodium pyrithione is approved for over-the-counter topical use in the United States as a treatment for dandruff and is the active ingredient in several antidandruff shampoos. In its industrial forms and strengths, it may be harmful by contact or ingestion. Sodium pyrithione can trigger a variety of responses, such as DNA damage in skin cells.

Sodium pyrithione is the sodium salt form of pyrithione, a fungistatic and antimicrobial derivative of aspergillic acid. Although the exact mechanism of action remains to be fully elucidated, Sodium pyrithione appears to interfere with membrane transport ultimately leading to a loss of metabolic control.
Metalworking fluids are fertile breeding grounds for microorganisms, particularly bacteria and fungi. Their unchecked growth causes fluids to deteriorate and degrades the fluid performance; this in turn causes damage to the work piece, cutting tools and fluid handling systems. Growth of microorganisms in fluids can also affect workers by causing foul odors, skin irritation and allergic reactions. These problems can be reduced or eliminated through the proper use of an antimicrobial agent. Sodium pyrithione 2000 Antimicrobial is a proprietary blend based on the antimicrobial active, sodium pyrithione (CAS # 3811-73-2) a fungicidal product with a successful history of use by the metalworking industry. Sodium pyrithione 2000 Antimicrobial exhibits increased efficacy against a wide variety of microorganisms found in metalworking fluid systems. In addition to its anticipated antifungal performance, Sodium pyrithione 2000 Antimicrobial also exhibits antibacterial efficacy.
The improved antimicrobial performance of Sodium pyrithione 2000 Antimicrobial is not a result of combinations with formaldehyde-based condensates, phenols, or isothiazoline-based products. This proprietary product is a blend of sodium pyrithione with a potentiator, and an amine coupler. This versatile antimicrobial blend can eliminate the need for formulating with multiple products. Sodium pyrithione 2000 Antimicrobial provides broad-spectrum antimicrobial control to a variety of metalworking fluid formulations and is suitable for use in both metalworking fluid concentrates and as a post treatment additive.

Addressing the blue color problem
Metalworking fluids have been known to change color upon the addition of pyrithione-based biocides. This is often referred to as the ‘blue-color problem’. The color change is due to the presence of ionic iron, which combines with pyrithione to form a highly colored, water insoluble compound. Iron can be introduced through raw materials, dilution water, or certain metalworking fluid operations. In the case of metalworking fluid concentrates, while the levels of ionic iron present are usually low, typically in the range of 5-25 ppm (parts per million), addition of sodium pyrithione will discolor the formulation, turning it gray or at times black. One method for addressing this problem is through the use of iron specific sequestering agents, like ethylenediaminetetraacetic acid (EDTA) or Arch’s Wayhib RW Chelating Agent. A more chronic problem for pryithione-based biocides is with high-speed cast iron machining operations. Metalworking fluid formulations used in these operations tend to accumulate and maintain high levels of ionic iron, making the use of sodium pyrithione unsuitable. In controlled laboratory tests dilute metalworking fluids known to contain 100-150 ppm of ironic iron did not discolor. In addition, this proprietary new antimicrobial can be used in formulations, which accumulate and maintain high levels of iron, while in use. Additions of Sodium pyrithione 2000 Antimicrobial to dilute metalworking fluids known to contain ionic iron in the range of 100-150 ppm did not turn blue, and the antimicrobial performance remains intact.

Below is a summary of data obtained using a test designed to evaluate the effectiveness of Sodium pyrithione 2000 Antimicrobial in three types of metalworking fluid formulations. The test protocol calls for one hundred milliliters of appropriately diluted fluid (20:1) to be placed into two hundred fifty milliliter Erlenmyer flasks. Sodium pyrithione 2000 Antimicrobial is added to each flask at the onset of the experiment. The treatment level used for this experiment was 1000 ppm, product as sold. Flasks are maintained at ambient temperature on an orbital shaker and challenged 3 times a week with a mixed inoculum of bacteria and fungi.

RECOMMENDED USE LEVELS
The recommended use level for Sodium pyrithione 2000 Antimicrobial in metalworking fluid concentrates (typically used at 20:1) is between 2.0-4.0%, product as sold. Post treatment dose levels of 1000-3000 ppm, product as sold, have been shown to be very effective in dilute metalworking fluids. The Following United States EPA Guidelines Should be Followed When Using This Biocide:
TO INHIBIT THE GROWTH OF FUNGI AND BACTERIA IN
AQUEOUS METALWORKING, CUTTING, COOLING AND
LUBRICATING FLUIDS: Add up to 5000 parts per million
(0. 5% v/v) of Sodium pyrithione 2000 Antimicrobial to the diluted fluid (5.0 gals per 1000 gals).
When adding fresh diluted fluid to compensate for dragout or other losses, add Sodium pyrithione 2000 Antimicrobial to makeup fluid according to the above directions. Frequent checks (at least once per week) of the bacterial and fungal population in the system should be made using standard microbiological plate count procedures or any of the commercial "dip-stick" type devices. When the bacterial count reaches 105 and/or the fungal count reaches 102 organisms per milliliter, add additional Sodium pyrithione 2000 Antimicrobial according to the above directions. The fluid should be checked at least once per day with a refractometer (or other suitable means) to determine if water loss by evaporation has occurred. Make-up water should be added daily to compensate for such losses. The fluid should be monitored at least once per week (depending on the metalworking operation involved) for the following: tramp oil, pH, odor, oil droplet size, and anticorrosion properties. If any of these parameters is outside the specifications established for the system in question, they should be brought up to specifications by the addition of suitable
additives or the fluid should be discarded and replaced after cleaning the system. Add Sodium pyrithione 2000 Antimicrobial
to the fresh fluid according to the above directions. Contaminated fluid systems should be cleaned prior to the addition of Sodium pyrithione 2000 Antimicrobial. Drain the system, clean with a cleaner designed for this purpose, rinse with water, and refill with fresh fluid. Sodium pyrithione 2000 Antimicrobial may be added to the fluid at the time it is prepared (diluted) or to the reservoir (sump) containing the fluid after it is put into use. If it is added to the reservoir, the fluid should be circulated after addition to ensure mixing.

LIGHT STABILITY
Sodium pyrithione 2000 Antimicrobial will gradually degrade when exposed to UV light. Formulations containing Sodium pyrithione 2000 Antimicrobial should be packaged in brown or opaque containers unless tests have shown that photodegradation is not a problem.
PH STABILITY
Sodium pyrithione 2000 Antimicrobial is effective over the pH range typical of most metalworking fluids. Below pH 4.5, the sodium salt is in equilibrium with free pyrithione and while pyrithione is microbiologically active, it is very unstable in the presence of light or oxygen.
CHEMICAL REACTIVITY
Oxidizing agents (such as peroxides and hypohalites) will convert pyrithione first to dipyrithione (2,2'-dithiobis-pyridine-1, 1'- dioxide), which is microbiologically active, and finally to pyrithione sulfinic or sulfonic acid, which are not microbiologically active compounds.

SAFETY INFORMATION
Material Safety Data Sheets containing appropriate health and safety advice on Sodium pyrithione 2000 Antimicrobial are available from your nearest regional office.
PACKAGING
Sodium pyrithione 2000 Antimicrobial is available from Rochester, NY in 45lb. And 500 lb. Containers and is available from Swords, Republic of Ireland in a 226.8 kg container. To place an order, call our order fulfillment group at 770-805-3301.
APPLICATION
For product application and formulation information please refer to Sodium pyrithione 2000 Antimicrobial product labeling.

Directions for Use of Sodium pyrithione
To inhibit the growth of fungi in aqueous metalworking, cutting, cooling and lubricating fluids: Add up to 1250 ppm (0.125% v/v) of Sodium pyrithione fungicide to the diluted fluid (1.25 gal per 1000 gal of solution). Typical recommended dose levels are between 200 and 500 ppm, product as sold. Different use and contamination conditions may require different levels of Sodium pyrithione fungicide and while compatible with most metalworking fluids physical and chemical compatibility testing is recommended. When adding fresh diluted fluid to compensate for dragout or other losses, add Sodium pyrithione fungicide to make-up fluid according to the above directions. Frequent checks (at least once per week) of the bacterial and fungal population in the system should be made using standard microbiological plate count procedures or any of the commercial “dip-stick” type devices. When the fungal count reaches 102 organisms per milliliter or greater, add additional Sodium pyrithione fungicide according to the above directions.
The fluid should be checked at least once per day with a refractometer (or other suitable means) to determine if water loss by evaporation has occurred. Make-up water should be added daily to compensate for such losses. The fluid should be monitored at least once per week (depending on the metalworking operation involved) for the following: tramp oil, pH, odor, oil droplet size, and anticorrosion properties. If any of these parameters is outside the specifications established for the system in question, they should be brought up to specifications by the addition of suitable additives or the fluid should be discarded and replaced after cleaning the system. Add Sodium pyrithione fungicide to the fresh fluid according to the above directions. Contaminated fluid systems should be cleaned prior to the addition of Sodium pyrithione fungicide. Drain the system, clean with a cleaner designed for this purpose, rinse with water, and refill with fresh fluid. Sodium pyrithione fungicide may be added to the fluid at the time it is prepared (diluted) or to the reservoir (sump) containing the fluid after it is put into use. If it is added to the reservoir, the fluid should be circulated after addition to ensure mixing.

To inhibit the growth of fungi in aqueous metalworking, cutting, cooling and lubricating concentrates: Add an amount that will give up to 1250 ppm in the diluted fluid. The amount required in the concentrate will depend on the end use dilution. For example: If the desired level of Sodium pyrithione fungicide in the diluted fluid is 200 ppm, and the end use dilution of the fluid is 5%, then a 0.4% concentration of Sodium pyrithione fungicide is required in the concentrate (200 ppm/0.05 = 4,000 ppm or 0.4%).

Heat Stability of Sodium pyrithione
Sodium pyrithione fungicide is stable at 100°C for at least 120 hours. At 150°C, the assay of Sodium pyrithione fungicide decreases 29% during a 48-hour period. The heat of decomposition, as measured under nitrogen by differential scanning calorimetry, is 158 cal/g for Sodium pyrithione fungicide.

pH Stability of Sodium pyrithione
Sodium pyrithione fungicide can be used over the pH range from 4.5 to 11.0. Below pH 4.5, the sodium salt is in equilibrium with free pyrithione. Pyrithione is active microbiologically, but is very unstable in the presence of light or oxygen. 
Light Stability of Sodium pyrithione
Sodium pyrithione fungicide will gradually degrade when exposed to light, depending on the nature of the formulation. Formulations containing Sodium pyrithione fungicide should be packaged in brown or opaque containers unless tests have shown that photodegradation is not a problem.
Sodium pyrithione Fungicide is a highly active, broad-spectrum antimicrobial agent that, when used at recommended concentrations, can help to prevent and minimize problems associated with fungal contamination. Sodium pyrithione is the 40% aqueous sodium salt derivative of pyrithione.
Sodium pyrithione functions as a wet-state preservative against bacteria and fungus in latex paints. Sodium pyrithione is a highly active, very effective water soluble sodium pyrithione. Offers pronounced growth-inhibiting activity against both yeasts and molds. Sodium pyrithione possesses non-irritating and non-sensitizing properties.

Sodium pyrithione is the common name of an organosulfur compound with molecular formula C5H5NOS, chosen as an abbreviation of pyridinethione, and found in the Persian shallot. It exists as a pair of tautomers, the major form being the thione 1-hydroxy-2(1H)-pyridinethione and the minor form being the thiol 2-mercaptopyridine N-oxide; it crystallises in the thione form.[5] It is usually prepared from either 2-bromopyridine,[1] 2-chloropyridine, or 2-chloropyridine N-oxide,[8] and is commercially available as both the neutral compound and its sodium salt.[1] It is used to prepare zinc Sodium pyrithione, which is used primarily to treat dandruff and seborrhoeic dermatitis in medicated shampoos, though is also an anti-fouling agent in paints.

Preparation
The preparation of Sodium pyrithione was first reported in 1950[13] by Shaw[14] and was prepared by reaction of 2-chloropyridine N-oxide with sodium hydrosulfide followed by acidification,[8] or more recently with sodium sulfide.[15] 2-chloropyridine N-oxide itself can be prepared from 2-chloropyridine using peracetic acid.[16] Another approach involves treating the same starting N-oxide with thiourea to afford pyridyl-2-isothiouronium chloride N-oxide which undergoes base hydrolysis to Sodium pyrithione.[1][17] 2-Bromopyridine can be oxidised to its N-oxide using a suitable peracid (as per 2-chloropyridine), both approaches being analogous to that reported in Organic Syntheses for the oxidation of pyridine to its N-oxide. A substitution reaction using either sodium dithionite (Na2S2O4) or sodium sulfide with sodium hydroxide will allow the replacement of the bromo substituent with a thiol functional group.
The alternative strategy is to form the mercaptan before introducing the N-oxide moiety. 2-Mercaptopyridine was originally synthesized in 1931 by heating 2-chloropyridine with calcium hydrosulfide,[6] an approach similar that first used to prepare Sodium pyrithione.[8] The analogous thiourea approach via a uronium salt was reported in 1958 and provides a more convenient route to 2-mercaptopyridine.[7] Oxidation to the N-oxide can then be undertaken.
The disulfide diSodium pyrithione, 2,2'-dithiobis(pyridine-N-oxide)
Sodium pyrithione is found as a natural product in the Allium stipitatum plant, an Asian species of onion, also known as the Persian shallot.[4] Its presence was detected using positive ion mass spectrometry using a DART ion source[19] and the disulfide diSodium pyrithione [de] (2,2'-disulfanediylbis(pyridine)-1,1'-dioxide) has been reported from the same species.[20] DiSodium pyrithione can be prepared in a laboratory by oxidation of Sodium pyrithione with chlorine in the presence of sodium hydroxide:
2 C5H4NOSH   +   Cl2   +   2 NaOH   →   ONC5H4–S–S–C5H4NO   +   2 NaCl   +   2 H2O
DiSodium pyrithione is used as a fungicide and bactericide,[8] and has been reported to possess novel cytotoxic activity by inducing apoptosis.[21]

Properties
Tautomerisation of the sodium salt of Sodium pyrithione
(thione form on the left, thiolate form on the right)
Sodium pyrithione exists as a pair of prototropes, a form of tautomerism whereby the rapid interconversion of constitutional isomers involves the shift of a single proton, in this case between the sulfur and oxygen atoms (shown in the infobox above).
Salts of the conjugate base of Sodium pyrithione can also be considered to exhibit tautomerism by notionally associating the sodium ion with whichever heteroatom bears the negative charge of the anion (as opposed to the formal charges associated with the N-oxide); however, considering the anion alone, this could also be described as an example of resonance.
Sodium pyrithione is a weak acid with pKa values of −1.95 and +4.6 (thiol proton), but is a markedly stronger acid than either of its parent compounds (pyridine-N-oxide and pyridine-2-thiol), both of which have pKa > 8.[22] It is only slightly soluble in water (2.5 g L−1) but is soluble in many organic solvents (including benzene, chloroform, dichloromethane, dimethylformamide, dimethylsulfoxide, and ethyl acetate) and slight solubility in others (diethyl ether, ethanol, methyl tert-butyl ether, and tetrahydrofuran).
Sodium pyrithione can be used as a source of hydroxyl radical in organic synthesis as it photochemically decomposes to HO• and (pyridin-2-yl)sulfanyl radical.

Applications
Structures of 1:2 complexes of zinc and the conjugate base of Sodium pyrithione
Top: Structural formula of the monomer
Bottom: Ball-and-stick model of the dimer
The conjugate base of Sodium pyrithione (pyrithionate ion) is an anion containing two donor atoms, a sulfur atom and an oxygen atom each bearing a negative formal charge; the nitrogen atom remains formally positively charged. The thiolate anion can be formed by reaction with sodium carbonate, and zinc Sodium pyrithione is formed when zinc chloride is added.[10] The anion can act as either a monodentate or bidentate ligand and forms a 1:2 complex with a zinc(II) metal centre. Zinc Sodium pyrithione has been used since the 1930s though its preparation was not disclosed until a 1955 British patent[13] in which Sodium pyrithione was reacted directly with hydrated zinc sulfate in ethanol.[9] In its monomeric form, zinc Sodium pyrithione has two of the anions chelated to a zinc centre with a tetrahedral geometry. In the solid state, it forms a dimer in which each zinc centre adopts a trigonal bipyramidal geometry with two of the anions acting as bridging ligands coordinated through the oxygen atoms in the axial positions.[26] In solution, the dimers dissociate via scission of zinc-oxygen bonds to each bridging ligand. Further dissociation of the monomer into its constituents can occur and is undesirable as the complex is more potent in medical applications; for this reason, zinc carbonate can be added to formulations as it inhibits the monomer dissociation.

Zinc Sodium pyrithione has a long history of use in medicated shampoos to treat dandruff and seborrhoeic dermatitis (dandruff can be considered a mild form of seborrheic dermatitis). It exhibits both antifungal and antimicrobial properties, inhibiting the Malassezia yeasts which promote these scalp conditions. The mechanisms by which this work are the subject of ongoing study. It can be used as an antibacterial agent against Staphylococcus and Streptococcus infections for conditions such as athlete's foot, eczema, psoriasis, and ringworm. It is known to be cytotoxic against Pityrosporum ovale, especially in combination with ketoconazole, which is the preferred formulation for seborrheic dermatitis.[11] Sodium pyrithione itself inhibits membrane transport processes in fungi.
Paints used in external environments sometimes include zinc Sodium pyrithione as a preventive against algae and mildew.

Sodium pyrithione zinc is an antibacterial and antifungal agent developed by scientists in the 1930's. Since then it has been used to treat seborrheic dermatitis of the scalp and other skin conditions such as eczema, athlete's foot, and vitiligo, as well as psoriasis. Because of its antifungal properties, it is commonly found in dandruff shampoo. Products containing Sodium pyrithione zinc are available today with and without prescription, and it is the main ingredient in many over-the-counter creams, lotions, soaps, and shampoos. It also has antibacterial properties and is effective against many pathogens from the Streptococcus and Staphylococcus genera. Sodium pyrithione zinc`s other medical applications include treatments of psoriasis, eczema, ringworm, fungus, athletes foot, dry skin, atopic dermatitis, tinea, and vitiligo. Its antifungal effect is thought to derive from its ability to disrupt membrane transport by blocking the proton pump that energizes the transport mechanism.

Stability: At room temperature in the dark, Sodium pyrithione is stable in the pH range 4.5 to 9.5. At 100°C it is stable for at least 120 hours, at 150°C 29 % of the substance has decomposed within 48 hours. In the light or in contact with weak oxidizing agents Sodium pyrithione is converted to the disulfide, 2,2-pyridyl-N-oxide disulfide. With stronger oxidizing agents or in alkaline solution (pH > 9.5) the substance is converted via a number of intermediates to the sulfonic acid; the reaction with reducing agents yields thiopyridine (Olin Corporation 1989f).

Sodium pyrithione zinc, or zinc Sodium pyrithione or zinc pyridinethione, is a coordination complex consisted of Sodium pyrithione ligands chelated to zinc (2+) ions via oxygen and sulfur centers. In the crystalline state, it exists as a centrosymmetric dimer. Due to its dynamic fungistatic and bacteriostatic properties, Sodium pyrithione zinc is used to treat dandruff and seborrheic dermatitis. Dandruff is a common scalp disease affecting >40% of the world's adult population, and may be caused by fungi such as Malassezia globosa and M. restricta 3.

Sodium pyrithione zinc is commonly found as an active ingredient in OTC antidandruff topical treatments such as shampoos. It mediates its action by increasing the cellular levels of copper, and damaging iron-sulfur clusters of proteins essential for fungal metabolism and growth 1. Due to low solubility, Sodium pyrithione zinc released from the topical formulations is deposited and retained relatively well onto the target skin surfaces 2. Other uses of Sodium pyrithione zinc include additive in antifouling outdoor paints and algaecide. While its use has been approved in the early 1960's by the FDA 4, safety and effectiveness of Sodium pyrithione zinc has been reported for decades. It is not shown to have any significant estrogenic activity according to the in vivo and in vitro assays 4.

Photodegradation in air
This point is regarded not to be relevant because:
- the vapour pressure of NaPT is very low, resulting in negligible exposure to the atmosphere.
- the calculation according to the Atkinson calculation method (5.1.1.001, ESPTF 7031-001) indicates a short half-life (53.8 hours) of sodium Sodium pyrithione in the atmosphere.
Summary of degradation
- Sodium Sodium pyrithione is hydrolytically stable.
- Sodium Sodium pyrithione passes the ready biodegradability test according to OECD 301B and biodegradation is rapid in soil, water-sediment, and STP. The degradation profile is well identified passing through several transient degradants to a final somewhat persistent degradant 2‑pyridine sulphonic acid (PSA).
- Photolysis is extremely rapid—again leading to the final somewhat persistent degradant 2‑pyridine sulphonic acid (PSA).
- The final degradant, PSA, passes the ready biodegradability test according to OECD 301B.

Photodegradation in water
A study of the photolysis rate of Sodium pyrithione has been carried out.
In a GLP study conducted according to US guideline US FDA Technical Assistance Document, Guideline 3.10 Photodegradation. 1987.) (5.1.3.001, EZPTF 7011-121) at a concentration of 10 mg/L, DT50for photolysis were determined to be <10 minutes at pH 5 and 7 and <15 minutes at pH 9. Degradants were not identified in this study.
A further study of the aqueous photolysis rate of Sodium pyrithione has also been conducted (refer to Table 5.1.2).
Study (5.1.3.003, EZPTF 7011-123) was conducted to determine the influence of concentration on photolysis rates. Photolysis was done in deionized water with zinc Sodium pyrithione concentrations of 0.1-1 μg/L, which are much closer to predicted environmental concentrations than those of the other two studies. Exposure to natural sunlight (42° N latitude) was done in quartz tubes at noon during the months of July through October. ZnPT was shown to have considerable absorptivity in the range of 290-400 nm, where photoactive solar radiation is available and photolysis in natural sunlight was very rapid. Measured photolysis half-lives ranged from 1.1 to 1.4 minutes in deionized water. Simultaneous exposure of the actinometer (o‑nitrobenzaldehyde) solutions allowed the calculation of photolysis disappearance quantum yields. Reproducibility at the very low concentrations used in this study required that several exposure experiments be run for each test compound and the results averaged. The quantum yield for ZnPT at 3.15 x 10-9M and 3.15 x 10-10M was 0.17 ± 0.06 (n = 4). This study also demonstrated that three metallic complexes of Sodium pyrithione (Zinc, Copper and Sodium) all exhibited the same photolysis rate at environmentally relevant concentrations.

Independent of the exposure route, Sodium pyrithione is of low toxicity. The typical symptom of intoxication in rats, mice and rabbits given single or multiple doses of the substance is reversible paralysis of the rear extremities. This effect is not seen in monkeys or dogs. In both these species effects on the pupillary reflex and photophobia were observed. Irreversible eye damage, however, has been seen only in species which have a tapetum lucidum, for example, the dog. Sodium pyrithione is readily absorbed from the gastrointestinal tract and through the intact skin. The substance is excreted rapidly in the form of urinary metabolites. Applied to rabbits, the substance causes slight irritation of the skin and eyes. Brief contact with aqueous solutions containing less than 1 % Sodium pyrithione produced no effects in animals or man; sensitization could not be demonstrated. Reproductive toxicity is not observed, either after dermal application to rats or rabbits or after oral administration to rats. Embryotoxicity develops in rats but not in rabbits after maternally toxic doses of Sodium pyrithione. Genotoxic effects of Sodium pyrithione could not be demonstrated in the Salmonella mutagenicity test, in the HPRT (hypoxanthine guanine phosphoribosyl transferase) test or in the test for DNA repair in rat hepatocytes. However, because the substance is cytotoxic, only low concentrations could be tested. Negative results were also obtained in vivo in the micronucleus test. Sodium pyrithione is not carcinogenic either after dermal application to mice or after oral administration to rats.
There are no reports of toxic effects of single exposures of persons to Sodium pyrithione. Reproductive toxicity, genotoxicity and carcinogenicity of Sodium pyrithione in man have not been described.