(4-Carboxybutyl)triphenylphosphonium bromide
[CAS# 17814-85-6]

Identification

• Classification: Organic raw materials >> Organic phosphine compound
• Name: (4-Carboxybutyl)triphenylphosphonium bromide
• Molecular Formula: C₂₃H₂₄O₂P.Br
• Molecular Weight: 443.32
• CAS Registry Number: 17814-85-6
• EC Number: 241-782-5
• SMILES: C1=CC=C(C=C1)[P+](CCCCC(=O)O)(C2=CC=CC=C2)C3=CC=CC=C3.[Br-]

Properties

• Melting point: 204-207 °C
• Flash point: 195 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	3	H301
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H312
Flammable solids	Flam. Sol.	2	H228
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332

Discovery and Applications

(4-Carboxybutyl)triphenylphosphonium bromide is an organophosphonium compound widely used in biochemical and pharmaceutical research due to its ability to target mitochondria selectively. The compound's discovery stems from research into mitochondrial targeting agents, where the positive charge of the triphenylphosphonium (TPP) moiety was found to facilitate the accumulation of such compounds in the mitochondria due to the organelle's negative membrane potential. This phenomenon allows for selective delivery of bioactive molecules to mitochondria, enhancing their effectiveness in treatments or studies that involve mitochondrial function or dysfunction.

The synthesis of (4-Carboxybutyl)triphenylphosphonium bromide involves the coupling of triphenylphosphine with 4-bromobutyric acid, followed by purification to obtain the bromide salt. The carboxybutyl group provides hydrophilic properties, while the TPP cation enhances its lipophilicity, allowing it to traverse biological membranes efficiently. This dual property makes it particularly useful in designing mitochondrial-targeted molecules.

Applications of (4-Carboxybutyl)triphenylphosphonium bromide are primarily focused on its role as a mitochondrial targeting vector. It is commonly used in the development of mitochondrial antioxidants, such as mitoquinone (MitoQ), where the phosphonium group delivers the antioxidant directly to the mitochondria, protecting cells from oxidative damage. This has profound implications for research into diseases characterized by mitochondrial dysfunction, including neurodegenerative diseases, cardiovascular disorders, and metabolic syndromes.

In addition to its use in targeting drugs to mitochondria, (4-Carboxybutyl)triphenylphosphonium bromide is also employed in studies on mitochondrial membrane potential and bioenergetics. By conjugating various probes or molecules to this compound, researchers can investigate mitochondrial dynamics, dysfunction, and the effects of potential therapeutics on mitochondrial health.

Overall, (4-Carboxybutyl)triphenylphosphonium bromide represents a significant advancement in mitochondrial research, providing a versatile tool for both basic research and therapeutic development. Its unique properties facilitate the delivery of drugs and probes directly to the mitochondria, making it an essential compound in mitochondrial-targeted therapies.

References

2022. A quantitative high-throughput screen identifies compounds that lower expression of the SCA2-and ALS-associated gene ATXN2. The Journal of biological chemistry.
DOI: 10.1016/j.jbc.2022.102228

2022. A Mitochondria-Targeted Phenylbutyric Acid Prodrug Confers Drastically Improved Anticancer Activities. Journal of Medicinal Chemistry.
DOI: 10.1021/acs.jmedchem.2c00640

2021. Synthesis and biological activities of novel mitochondria-targeted artemisinin ester derivatives. Bioorganic & Medicinal Chemistry Letters.
DOI: 10.1016/j.bmcl.2021.127912