108535-01-9

Basic information

• Product Name: 5,5'-dihydroxy-4,4'-bitryptamine
• Synonyms: 5,5'-dihydroxy-4,4'-bitryptamine;3,3'-Bis(2-aminoethyl)-4,4'-bi[1H-indole-5-ol];5,5'-Dihydroxy-4,4'-bi(1H-indole-3-ethanamine)
• CAS NO: 108535-01-9
• Molecular Formula: C₂₀H₂₂N₄O₂
• Molecular Weight: 350.41
• Mol File: 108535-01-9.mol

Chemical Properties

• Boiling Point: 689.7°Cat760mmHg
• Flash Point: 370.9°C
• Appearance: /
• Density: 1.404g/cm³
• CAS DataBase Reference: 5,5'-dihydroxy-4,4'-bitryptamine(CAS DataBase Reference)
• NIST Chemistry Reference: 5,5'-dihydroxy-4,4'-bitryptamine(108535-01-9)
• EPA Substance Registry System: 5,5'-dihydroxy-4,4'-bitryptamine(108535-01-9)

Safety Data

• Hazardous Substances Data: 108535-01-9(Hazardous Substances Data)

Upstream product

• 153-98-0 serotonin hydrochloride 
• 52-90-4 L-Cysteine 
• 50-67-9 3-(2-aminoethyl)-1H-indol-5-ol 
• 69-89-6 xanthine 

Relevant articles and documents

Oxidation of serotonin by superoxide radical: Implications to neurodegenerative brain disorders

Many new lines of evidence implicate both superoxide anion radical (O2.-) and biogenic amine neurotransmitters in the pathological mechanisms that underlie neuronal damage caused by methamphetamine (MA), glutamate- mediated oxidative toxicity, ischemia-reperfusion, and other neurodegenerative brain disorders. In this investigation the oxidation of 5- hydroxytryptamine (5-HT, serotonin) by an O2.- -generating system (xanthine/xanthine oxidase) in buffered aqueous solution at pH 7.4 has been studied. The major product of the O2.- -mediated oxidation of 5-HT is tryptamine-4,5-dione (T-4,5-D). However, O2.- and H2O2, cogenerated by the xanthine oxidase-mediated oxidation of xanthine to uric acid, together react with trace levels of iron that contaminate buffer constituents to give a chemically ill-defined oxo-iron species. This species mediates the oxidation of 5-HT to a C(4)-centered carbocation intermediate that reacts with 5-HT to give 5,5'-dihydroxy-4,4'-bitryptamine (4,4'-D) and with uric acid to give 9-[3-(2-aminoethyl)-5-hydroxy-1H-indol-4-yl]-2,6,8-triketo- 1H,3H,7H-purine (7) as the major products. These products differ from those formed in the HO.-mediated oxidation of 5-HT under similar conditions. When the reaction is carried out in the presence of the intraneuronal nucleophile glutathione (GSH), T-4,5-D is scavenged to give 7-(S-glutathionyl)tryptamine- 4,5-dione, whereas the putative carbocation intermediate is scavenged to give 4-(S-glutathionyl)-5-hydroxytryptamine. T-4,5-D also reacts with the sulfhydryl residues of a model protein, alcohol dehydrogenase, and inhibits its activity. Previous investigators have proposed that T-4,5-D is a serotonergic neurotoxin. This raises the possibility that T-4,5-D and perhaps other putative intraneuronal metabolites formed by the O2.-/H2O2/oxo- iron-mediated oxidations of 5-HT might be endotoxins that contribute to neurodegeneration in brain regions innervated by serotonergic neurons caused by MA, ischemia-reperfusion, and other neurodegenerative brain disorders.

Influence of L-Cysteine on the Oxidation Chemistry of Serotonin

L-Cysteine (CySH) intervenes in the normal electrochemically driven oxidation of 5-hydroxytryptamine (5-HT; serotonin) at physiological pH by scavenging the quinone imine proximate oxidation product of this indolic neurotransmitter to give 4-S-cysteinyl-5-hydroxytryptamine (4-S-CyS-5-HT). The latter cysteinyl conjugate is more easily electro-oxidized than 5-HT and, in the presence of free CySH, undergoes a complex series of reactions leading to 8-(2-aminoethyl)-1,2,3,5,6,9-hexahydro-5,9-dioxo-pyrrolobenzothiazine-2-carboxylic acid (20) and N--3-(2-aminoethyl)-1,4-dihydro-4-oxo-5H-indol-5-ylidene>-L-cysteine (4). CySH also reacts with another normal oxidation product of 5-HT, tryptamine-4,5-dione, to give 4 and 20. There is evidence that aberrant oxidative metabolism of 5-HT occurs in the brains of Alzheimer's Disease patients. In the event that such reactions occur in the cytoplasm of serotonergic nerve terminals or axons they would necessarily expose electrophilic intermediates and products to the intraneuronal nucleophiles CySH and GSH. The results of this study indicate that 4 and 20 might represent aberrant oxidative metabolites formed in such reactions. However, the ease of oxidation of 4-S-CyS-5-HT compared to 5-HT suggest that this conjugate is likely to be only a transient species in vivo under conditions where the neurotransmitter is oxidized.

Further insights into the oxidation chemistry of 5-hydroxytryptamine

An important product of electrochemical oxidation of 5-hydroxytryptamine (5-HT) in acid solution is the purple compound tryptamine-4,5-dione (6). However, any attempt to concentrate a solution containing 6 causes it to disappear. The most important reaction of 6 is dimerization to give another purple compound 7,7'-bi-(5-hydroxytryptamine-4-one). Dione 6 can also apparently react with 2,4'-bi-5-hydroxytryptamine to give the trimer 4-[7'-(tryptamine-4,5-dione)]-2,4'-bi-5-hydroxytryptamine. Finally, 6 and other oxidation products of 5-HT react during the concentration step to yield what appears to be a trimer or perhaps a higher oligomer. This oligomer has not been identified, but it has been shown to decompose to give, in part, the neurotoxin 5-hydroxytryptamine-4,7-dione.