DL-Penicillamine
[CAS# 52-66-4]

Identification

• Classification: API >> Other chemicals
• Name: DL-Penicillamine
• Synonyms: DMC; NSC 22880; NSC 44656
• Protein Sequence: X
• Molecular Formula: C₅H₁₁NO₂S
• Molecular Weight: 149.21
• CAS Registry Number: 52-66-4
• EC Number: 200-147-2
• SMILES: CC(C)(C(C(=O)O)N)S

Properties

• Solubility: Sparingly soluble (31 g/L) (25 ºC), Calc.^*
• Density: 1.204±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Melting point: 212 ºC (dec.)^**
• Boiling point: 251.8±35.0 ºC (760 Torr), Calc.^*
• alpha: 25 º (Expl.)
• Flash point: 106.1±25.9 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2013 ACD/Labs)

^** Matsumoto, Takeshi; J. Fac. Sci. Hokkaido Univ. 1957, (Ser. III 5), P17-36.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

DL-Penicillamine is a sulfur-containing amino acid derivative recognized for its medicinal importance. Structurally, it is a thio analog of valine, characterized by the presence of a thiol (-SH) group attached to a branched carbon skeleton. This unique structure imparts significant chemical and biological reactivity, making DL-penicillamine a valuable therapeutic agent.

The discovery of DL-penicillamine can be traced back to early investigations into penicillin degradation products. Penicillamine was first identified as a by-product during the acid hydrolysis of penicillin, from which its name is derived. Early research established its structural uniqueness and hinted at its potential as a biological chelating agent. Subsequent synthetic developments allowed for large-scale production and the exploration of its pharmacological properties.

DL-Penicillamine is best known for its application in treating heavy metal poisoning, particularly with metals such as lead, copper, and mercury. The thiol group forms stable complexes with metal ions, facilitating their excretion from the body. This property makes it an effective chelating agent in conditions like Wilson’s disease, a genetic disorder characterized by copper accumulation. In such cases, penicillamine therapy helps manage copper levels, preventing organ damage.

In rheumatology, DL-penicillamine has been used to manage rheumatoid arthritis. Its mechanism of action involves modulating immune responses and reducing inflammation, although its exact pathways remain partially understood. Despite its efficacy, the drug's use in this context has declined due to the availability of biologic agents with improved safety profiles.

DL-Penicillamine is also of interest in biochemistry and material science. Its thiol group participates in redox reactions and forms disulfide bonds, making it a useful reagent in protein chemistry for studying disulfide linkages. Additionally, its chiral nature has been exploited in the development of asymmetric synthesis techniques and as a resolving agent in stereochemical studies.

Synthesis of DL-penicillamine involves multistep chemical processes starting from simple precursors like isobutyraldehyde. Modern approaches aim to improve yields and reduce the environmental impact of its production, aligning with sustainable chemistry principles.

However, the use of DL-penicillamine is not without challenges. Side effects, including skin rashes, gastrointestinal disturbances, and autoimmune reactions, have been reported, necessitating careful monitoring during therapy. Advances in formulation and delivery systems continue to be explored to mitigate these adverse effects.

Overall, DL-penicillamine remains a compound of enduring relevance, bridging medicinal chemistry and clinical applications. Its ability to interact with metals and proteins has paved the way for innovative therapies and research tools, ensuring its place in both therapeutic and scientific domains.

References

Walshe JM (1956). Penicillamine, a new oral therapy for Wilson’s disease. The American Journal of Medicine, 21(4), 487-495.

Harris ED and Sacher RS (1984). The use of penicillamine in rheumatoid arthritis: Mechanisms of action and clinical effects. Annals of the Rheumatic Diseases, 43(2), 257-262.

Nguyen TQ and Salsbury FR (2020). Advances in penicillamine-based complexes for biomedical applications. Coordination Chemistry Reviews, 420, 213434.