Pyrithione (1121-30-8) Physical and Chemical Properties
Pyrithione
A pyridinethione-class antimicrobial that functions as a ligand in zinc complexes and is used in formulations for personal care and industrial biocide applications.
| CAS Number | 1121-30-8 |
| Family | Pyridines (pyridinethiones) |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP |
Pyrithione is a small, heteroaromatic thione/oxide derived from pyridine, formally described as 1-hydroxypyridine-2-thione (tautomeric with pyridine-2-thiol N-oxide). The molecule contains a pyridinyl ring functionalized with adjacent sulfur and N–O/H functionality that provides a mixed soft (sulfur) and hard (oxygen) donor set. This ambident donor motif enables chelation to divalent metal ions (notably \(\ce{Zn^2+}\)) and underpins the formation of coordination complexes that are pharmacologically and industrially important. The neutral parent has limited intrinsic lipophilicity and a modest topological polar surface area, but metal complexation substantially alters its solubility and membrane interaction behavior.
Electronically, pyrithione exhibits resonance between thiol/thiolate, thione and N‑oxide–type descriptions; the S and O centers confer nucleophilicity and coordinate to metals in bidentate modes. Acid–base behavior is characterized by a weakly acidic thiol functionality in some environments and by facile tautomerism; the free ligand is largely neutral under ambient conditions. The compound is moderately polar (XLogP ≈ 0.5) with one hydrogen-bond donor and two acceptors, which together with low rotatability favors defined solid-state packing and limited conformational flexibility. Oxidation and hydrolysis susceptibilities are low under typical handling conditions, but metal chelation and redox-active transition metals can change reactivity and biological activity.
Pyrithione is widely used industrially and pharmaceutically in its metal-chelated forms (notably zinc pyrithione) as a fungistatic and bacteriostatic agent in topical formulations and as a biocide in paints and metalworking fluids. Common commercial grades reported for this substance include: EP.
Basic Physical Properties
Density
No experimentally established value for this property is available in the current data context.
Melting Point
No experimentally established value for this property is available in the current data context.
Boiling Point
A numerical boiling point value of 100 is present in the available data, but no unit was specified for this value in the supplied context. Treat the value "100" as reported without an assigned unit in this dataset.
Vapor Pressure
No experimentally established value for this property is available in the current data context.
Flash Point
No experimentally established value for this property is available in the current data context.
Chemical Properties
Solubility and Phase Behavior
The free pyrithione ligand is poorly soluble in water, but its metal salts (most commonly the zinc complex) exhibit enhanced aqueous dispersibility relative to the free ligand. The supplied data notes: "Soluble in cold water (Zinc salt)", indicating that complexation to \(\ce{Zn^2+}\) substantially increases apparent solubility and surface deposition behavior. In formulations, low intrinsic solubility of the metal complex promotes retention on treated surfaces (e.g., skin or paint films), which is exploited in topical and antifouling applications. Phase behavior therefore depends strongly on metal counterion, pH, and formulation excipients.
Reactivity and Stability
Pyrithione is chemically stable under neutral and mildly acidic/basic conditions typical of storage and topical use. The ligand is capable of forming stable coordination complexes with divalent metal ions via oxygen and sulfur donor atoms; formation and dissociation of these complexes modulate biological activity (ionophore behavior) and solubility. Although not highly susceptible to simple hydrolysis or oxidative cleavage under standard conditions, interaction with redox‑active metal centers or strong oxidants can alter the S-containing functional group. The N–O/thione tautomerism provides internal stabilization but also allows reactivity pathways for conjugation (e.g., S‑glucuronidation in biological systems).
Thermodynamic Data
Standard Enthalpies and Heat Capacity
No experimentally established value for this property is available in the current data context.
Molecular Parameters
Molecular Weight and Formula
- Molecular formula: \(\ce{C5H5NOS}\)
- Molecular weight: 127.17 \(\mathrm{g}\,\mathrm{mol}^{-1}\)
- Exact mass / Monoisotopic mass: 127.00918496
Additional computed descriptors from the molecular data: heavy atom count = 8; complexity = 162; formal charge = 0; covalently-bonded unit count = 1.
LogP and Polarity
- XLogP3‑AA: 0.5
- Topological polar surface area (TPSA): 55.6 Å^2 (reported as 55.6)
- Hydrogen-bond donor count: 1
- Hydrogen-bond acceptor count: 2
These values indicate modest lipophilicity with appreciable polarity and hydrogen‑bonding capacity for a small heteroaromatic compound. The TPSA and H‑bond counts are consistent with limited passive membrane permeability as the free ligand, while metal complexation (e.g., with \(\ce{Zn^2+}\)) changes lipophilicity and membrane interactions and enables ionophore-mediated transport phenomena.
Structural Features
Pyrithione is a substituted pyridine featuring adjacent sulfur and N–O/H functionality at the 2‑position. The structure is commonly represented by the IUPAC name 1‑hydroxypyridine‑2‑thione (1‑hydroxypyridine‑2(1H)‑thione). Key structural/solid-state observations:
- The ligand chelates metals through sulfur and oxygen donor atoms to form coordination complexes (zinc pyrithione is a well-known example).
- In the crystalline state the zinc complex is reported to exist as a centrosymmetric dimer; single‑crystal data for the ligand and complexes show defined packing motifs.
- Conformationally rigid: rotatable bond count = 0, which correlates with well-defined crystal packing and reproducible spectroscopic signatures.
Crystal lattice parameters (reported values for crystalline samples in the available context): a = 6.231, b = 7.935, c = 11.667; α = 90.00°, β = 92.09°, γ = 90.00°; Z = 4; Z' = 1. These values indicate a monoclinic space group (P 1 21/n 1; Hall: -P 2yn) with good-quality refinement (residual factor ~0.0594) in the cited crystallographic depositions.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS: 1121-30-8
- European Community (EC) number(s): 214-329-4; 214-328-9
- UNII: 6GK82EC25D
- InChI: InChI=1S/C5H5NOS/c7-6-4-2-1-3-5(6)8/h1-4,7H
- InChIKey: YBBJKCMMCRQZMA-UHFFFAOYSA-N
- SMILES: C1=CC(=S)N(C=C1)O
(When used computationally, SMILES, InChI and InChIKey should be handled as exact identifiers and are provided above in-line as supplied.)
Synonyms and Structural Names
Common synonyms and structural names appearing in the available context include: pyrithione; 2‑pyridinethiol 1‑oxide; 1‑hydroxypyridine‑2‑thione; pyridine‑2‑thiol N‑oxide; 2‑mercaptopyridine N‑oxide; Omadine. The IUPAC/acceptable systematic name given: 1‑hydroxypyridine‑2‑thione.
Industrial and Commercial Applications
Representative Uses and Industry Sectors
Pyrithione and its metal salts are used primarily as antimicrobial agents and biocides. Representative sectors and uses reported in the available context:
- Topical antifungal/antidandruff actives (zinc pyrithione) in rinse‑off formulations and medicated shampoos for control of Malassezia species associated with dandruff and seborrheic dermatitis.
- Biocidal additive in paints and coatings (antifouling/anti‑algal applications).
- Biocide in metalworking fluids, lubricants, inks and certain industrial formulations where microbial control is required.
These uses exploit the chelating and ionophore properties of the pyrithione ligand when coordinated to metal ions, which modulate both activity and deposition onto surfaces.
Role in Synthesis or Formulations
Pyrithione functions as a ligand and as an active antimicrobial moiety. In formulations the zinc salt (zinc pyrithione) is the principal commercial form because coordination to \(\ce{Zn^2+}\) stabilizes the active agent, alters solubility/retention, and reduces volatility. The sodium salt is used where increased water solubility is required (for specific industrial biocidal applications). In synthetic chemistry the ligand can be used to prepare metal complexes with tailored antimicrobial or enzyme‑inhibitory properties.
If a concise, proprietary formulation summary is required for procurement or manufacturing, selection is typically based on the intended matrix (aqueous vs. nonaqueous), required delivery (surface deposition vs. soluble biocide), and regulatory acceptance for the target application.
Safety and Handling Overview
Acute and Occupational Toxicity
Available hazard classifications and statements reported in the provided context include acute toxicity and irritation endpoints:
- GHS hazard statements (examples reported): H301 (Toxic if swallowed), H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation).
- Hazard classes (aggregated notifications): Acute Tox. 3; Skin Irrit. 2; Eye Irrit. 2; STOT SE 3.
- Adverse effects: skin sensitization and allergic contact dermatitis have been reported in occupational settings; pyrithione can act as a skin sensitizer.
Occupational exposure control should therefore assume potential for dermal and respiratory irritation and possible systemic toxicity if ingested. Engineering controls, appropriate personal protective equipment (chemical‑resistant gloves, eye protection, and respiratory protection when aerosolization or dust is possible), and skin‑contact minimization are prudent.
Storage and Handling Considerations
Store pyrithione and its salts in a cool, dry, well‑ventilated area away from strong oxidants and incompatible metals. Avoid dust formation and airborne dispersal; handle solids in closed systems or with local exhaust ventilation. Use standard good industrial hygiene practices: avoid ingestion, inhalation and skin/eye contact; decontaminate spill residues promptly and provide facilities for eye wash and emergency showering. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
For formulation manufacturing and QC, consider the following quality and safety attributes: control of particle size and polymorphic form (solid-state packing can affect dissolution and deposition), elemental metal counterion identity (zinc vs. sodium), and impurity profile (residual solvents and degradation products). Common commercial grade designation reported for this substance: EP.
