Carbocysteine (638-23-3) Physical and Chemical Properties
Carbocysteine
S‑Carboxymethyl‑L‑cysteine, a polar thioether amino‑acid derivative used as a small‑molecule mucolytic API and research chemical for formulation development, analytical QC and R&D workflows.
| CAS Number | 638-23-3 |
| Family | Amino acid derivatives |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP, JP |
Carbocysteine is an S‑carboxymethyl derivative of L‑cysteine and belongs to the class of amino‑acid–derived thioethers. Structurally it is an L‑alpha‑amino acid in which the cysteine thiol hydrogen is substituted by a carboxymethyl group, giving an overall neutral covalent molecule that carries ionizable functionalities (one or more carboxyl groups and an amino group). The molecular skeleton combines a short aliphatic backbone with a sulfide linkage and two terminal carboxylate/acid moieties, producing a compact, highly polar structure with multiple hydrogen‑bond donors and acceptors.
Electronically, carbocysteine combines a localized sulfur atom in a thioether linkage (reduced oxidation state relative to sulfoxides/sulfones) with strongly electron‑withdrawing carboxylate functionality when deprotonated. The presence of a primary amine and carboxyl groups gives typical amino‑acid acid–base behaviour: under physiological conditions it exists predominantly as a zwitterion (protonated amine, deprotonated carboxylate). High topological polar surface area and low partition coefficients indicate strong hydrophilicity and limited passive membrane permeability; the thioether reduces susceptibility to disulfide formation but remains a site for oxidative metabolism (sulfoxidation).
Functionally, carbocysteine is used pharmaceutically as a mucolytic and expectorant owing to its ability to alter mucin composition and reduce sputum viscosity; it also exhibits in‑vitro antioxidant and anti‑inflammatory effects. Common commercial grades reported for this substance include: EP, JP.
Basic Physicochemical Properties
Density and Solid-State Form
No experimentally established value for this property is available in the current data context.
Solid‑state form: carbocysteine is typically encountered as a crystalline amino‑acid salt in its L‑isomeric form; it contains a defined stereocenter (one defined atom stereocenter) corresponding to the (2R) configuration.
Melting Point
Melting point (reported): 185–187 \(\,^\circ\mathrm{C}\).
This relatively high melting range is consistent with a small, highly polar crystalline amino‑acid derivative that forms extensive intermolecular hydrogen bonds in the solid state.
Solubility and Dissolution Behavior
Aqueous solubility (reported): 1.6 \(\mathrm{g}\,\mathrm{L}^{-1}\).
Given the high topological polar surface area (TPSA = 126 Ų) and multiple hydrogen‑bond donors (3) and acceptors (6), carbocysteine is hydrophilic and dissolves preferentially in polar solvents (water). Solubility and dissolution rate are influenced by pH because the carboxyl groups will be ionized across most of the pH range relevant to formulation and physiology, promoting aqueous solubility but also producing a zwitterionic species at near‑neutral pH that can affect crystallinity and dissolution kinetics.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
Reported dissociation constant: \(\mathrm{p}K_a = 1.84\).
The reported \(\mathrm{p}K_a\) corresponds to a strongly acidic site (likely a carboxyl proton). At physiological \(\mathrm{pH}\) the carboxyl group(s) are effectively deprotonated while the amino group will be protonated, resulting in a zwitterionic form. No additional experimentally established dissociation constants for other ionizable centres (for example the amino group) are available in the current data context.
Reactivity and Stability
Carbocysteine contains a thioether (sulfanyl) linkage rather than a free thiol, which reduces direct thiol‑disulfide exchange and limits chemical oxidation to disulfide formation relative to free cysteine. However, the sulfur atom remains susceptible to metabolic and chemical oxidation (sulfoxidation) to sulfoxide and, less commonly, sulfone derivatives. Reported metabolic transformations include sulfoxidation, acetylation and decarboxylation; sulfoxidation is a principal metabolic pathway in vivo. Hydrolytic instability is not a primary concern under neutral aqueous storage, but decarboxylation and oxidative degradation can occur under forced degradation conditions (strong oxidative or high‑temperature environments). Formulations and manufacturing steps should therefore minimize exposure to strong oxidants and excessive heat.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: \(\ce{C5H9NO4S}\)
Molecular weight (reported): 179.20 g·mol^{-1}
Exact/monoisotopic mass: 179.02522894
The small molecular weight and single stereocenter correspond to a low‑mass, chiral amino‑acid derivative.
LogP and Structural Features
Reported partitioning descriptors: XLogP = -3.1 (computed); LogP (experimental/other reported) = -4.24.
These strongly negative partition coefficients confirm pronounced hydrophilicity and low intrinsic lipophilicity. Structural contributors to low LogP include two carboxyl moieties (or one carboxyl plus carboxymethyl substitution), a protonatable amine, and multiple hydrogen‑bonding functionalities. Topological polar surface area (TPSA) = 126 Ų is high for a small molecule, consistent with limited passive membrane permeation and favourable aqueous solvation.
Additional computed descriptors: hydrogen‑bond donor count = 3; hydrogen‑bond acceptor count = 6; rotatable bond count = 5; heavy atom count = 11; formal charge = 0 (neutral covalent parent).
Structural Identifiers (SMILES, InChI)
SMILES: C([C@@H](C(=O)O)N)SCC(=O)O
InChI: InChI=1S/C5H9NO4S/c6-3(5(9)10)1-11-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1
InChIKey: GBFLZEXEOZUWRN-VKHMYHEASA-N
These identifiers correspond to the L‑isomeric S‑carboxymethyl derivative of cysteine with a single defined stereocentre.
Identifiers and Synonyms
Registry Numbers and Codes
CAS Number: 638-23-3
European Community (EC) Number: 211-327-5
UNII: 740J2QX53R
Additional registry and database identifiers are present in regulatory and cheminformatics resources; the above are reported registry codes associated with the compound.
Synonyms and Brand-Independent Names
Representative synonyms (selected from available nomenclature): Carbocysteine; Carbocisteine; S‑Carboxymethyl‑L‑cysteine; 3‑(Carboxymethylthio)alanine; (2R)-2‑amino‑3-(carboxymethylsulfanyl)propanoic acid. A broader list of depositor‑supplied synonyms and INN/USAN variants exist for supply chain and labeling purposes.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Carbocysteine is used as an active pharmaceutical ingredient with mucolytic and expectorant properties. It modulates mucin composition and reduces sputum viscosity, which facilitates mucus clearance and can reduce the risk of infection related to mucus accumulation in obstructive respiratory conditions. The compound also exhibits antioxidant and anti‑inflammatory activity in vitro, which contributes to its therapeutic profile as a respiratory tract agent.
Regulatory status varies by jurisdiction; it is marketed in multiple regions as an over‑the‑counter or prescription mucolytic in oral and topical formulations. Serious adverse pulmonary effects have been reported in pediatric populations in some regulatory reviews; therefore clinical and regulatory contexts influence its approved uses.
Formulation and Development Contexts
Carbocysteine is formulated for oral administration (tablets, capsules, syrups) and has also been used in topical nasal preparations. Key formulation considerations include its zwitterionic character, moderate aqueous solubility (1.6 \(\mathrm{g}\,\mathrm{L}^{-1}\)), and susceptibility to oxidative metabolism/degradation; antioxidants, pH control and protection from oxidizing agents are typical stabilisation strategies. Its low lipophilicity and high TPSA reduce the need for solubilizing excipients to achieve aqueous dispersion, but crystalline habit and polymorphism can affect dissolution and bioavailability and therefore should be characterized during development.
If detailed application summaries are required for a specific market or formulation, refer to appropriate regulatory and product development documentation.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Carbocysteine is supplied in typical industry grade categories: pharmaceutical (for finished dose manufacture), analytical (reference standards), and technical (for research and non‑clinical uses). Reported commercial grades include EP and JP.
Pharmaceutical grade material will be expected to comply with pharmacopeial monograph requirements where applicable; analytical grade material is used for assay and reference testing.
General Quality Attributes (Qualitative Description)
Quality attributes relevant to procurement and quality control include stereochemical purity (L‑isomer content), assay (active content), residual solvents, water content, particle size/crystallinity, and limits for oxidative and other degradants. Typical specifications focus on identity (IR, NMR, MS), assay by chromatography, and impurity profiling; control of oxidative impurities (sulfoxides) is often emphasized due to the sulfur center.
No supplier‑specific assay percentages or impurity limits are provided in the current data context.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Carbocysteine is generally considered to have a mucolytic therapeutic margin when used as directed in adults, but serious and in some instances fatal paradoxical respiratory reactions have been reported in children following therapy, including worsening dyspnea and respiratory distress; pediatric use and dosing require regulatory and clinical oversight. Reported classifications in hazard notifications include skin corrosion/irritation concerns in a minority of reports (H314 reported in ~11% of notified classifications), indicating potential for severe skin and eye damage under certain conditions or with specific formulations/impurities.
Systemic toxicity and pharmacokinetic information indicate rapid oral absorption with peak plasma concentrations within 1–1.7 hours and substantial renal excretion of unchanged drug (approximately 30–60% recovered in urine). Metabolism includes sulfoxidation and other hepatic transformations; variability in metabolic capacity can affect exposure.
Storage and Handling Guidelines
Handle carbocysteine using standard precautions for fine, hygroscopic, polar organic solids: use appropriate personal protective equipment (gloves, eye protection, lab coat), control dust generation, and avoid inhalation and contact with skin and eyes. Store in a tightly closed container in a cool, well‑ventilated area away from strong oxidizing agents and excessive heat to limit oxidative degradation and maintain stability. For spill response, extinguishing media selection and disposal, consult the product‑specific Safety Data Sheet (SDS) and follow local regulatory and workplace safety procedures.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
