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Usage

Uses

Used in Pharmaceutical Industry:
2,2'-dithiobis(ethylamine) is used as a building block for the synthesis of various pharmaceutical compounds due to its reactive amine groups and cleavable disulfide bond. 2,2'-dithiobis(ethylamine) can be incorporated into drug molecules to enhance their stability, solubility, and bioavailability.
Used in Chemical Synthesis:
In the field of chemical synthesis, 2,2'-dithiobis(ethylamine) serves as a versatile reagent for the formation of disulfide-containing compounds. Its ability to participate in reactions with carboxylic acids and other carbonyl compounds makes it a valuable tool for creating complex molecular structures.
Used in Biochemistry and Molecular Biology:
2,2'-dithiobis(ethylamine) is used as a crosslinking agent for proteins and other biomolecules. The cleavable disulfide bond allows for the controlled formation of disulfide bridges between molecules, which can be useful in studying protein-protein interactions, enzyme activity, and the structure of biological macromolecules.
Used in Material Science:
In material science, 2,2'-dithiobis(ethylamine) can be utilized in the development of novel materials with specific properties. 2,2'-dithiobis(ethylamine)'s ability to form disulfide bonds can be exploited to create self-assembling structures, hydrogels, and other materials with tailored characteristics for various applications, such as drug delivery, tissue engineering, and sensors.

Upstream product

• 56-89-3 cysteine disulfide 
• 56-89-3 L-cystine 
• 2937-53-3 2-aminoethylthiosulfonic acid 
• 5205-42-5 N,N'-(2,2'-disulfanediylbis(ethane-2,1-diyl))dibenzamide 
• 60-23-1 Cysteamine 
• 156-57-0 2-mercaptoethylamine hydrochloride 
• 13244-81-0 (S)-2-Amino-4-[(R)-2-(2-amino-ethyldisulfanyl)-1-(carboxymethyl-carbamoyl)-ethylcarbamoyl]-butyric acid 
• 67616-42-6 S-nitroso-2-aminoethanethiol 
• 71899-86-0 S-<(3-carboxy-4-nitrophenyl)thio>-2-aminoethanethiol 
• 7647-01-0 hydrogenchloride 
• 64-19-7 acetic acid 
• 504-78-9 1,3-thiazolidine 
• 7553-56-2 iodine 
• 109653-49-8 2,2'-(disulfanediylbis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) 

Downstream Products

• 87503-54-6 bis-{2-[(N,N-phthaloyl-β-alanyl)-amino]-ethyl}-disulfide 
• 118767-15-0 bis-(2-{[N-(toluene-4-sulfonyl)-β-alanyl]-amino}-ethyl)-disulfide 
• 1779-81-3 4,5-Dihydro-thiazol-2-ylamin 
• 60-23-1 Cysteamine 
• 107-35-7 Tau 
• 104071-84-3 bis-{2-[(N-benzyloxycarbonyl-β-alanyl)-amino]-ethyl}-disulfide 
• 638-44-8 N,N'-(dithiodiethylene)bisacetamide 
• 83626-62-4 bis-{2-[(N-acetyl-sulfanilyl)-amino]-ethyl}-disulfide 
• 14348-35-7 2-Amino-N-{2-[2-(2-amino-3-phenyl-propionylamino)-ethyldisulfanyl]-ethyl}-3-phenyl-propionamide 
• 138148-35-3 D-pantethine 
• 7739-00-6 [1-(4-Chloro-phenyl)-meth-(E)-ylidene]-[2-(2-{[1-(4-chloro-phenyl)-meth-(E)-ylidene]-amino}-ethyldisulfanyl)-ethyl]-amine 
• 17669-15-7 N,N'-Bis-<γ-(N-p-toluolsulfonyl)-L-glutamyl>-cystamin 
• 112614-14-9 bis<2-(E-2-hexenoylamino)ethyl> disulfide 
• 112614-16-1 bis<2-(E-2-octenoylamino)ethyl> disulfide 

Relevant academic research and scientific papers

Oxyhalogen-sulfur chemistry - Kinetics and mechanism of the oxidation of cysteamine by acidic iodate and iodine

The oxidation of cysteamine by iodate and aqueous iodine has been studied in neutral to mildly acidic conditions. The reaction is relatively slow and is heavily dependent on acid concentration. The reaction dynamics are complex and display clock behavior, transient iodine production, and even oligooscillatory production of iodine, depending upon initial conditions. The oxidation product was the cysteamine dimer (cystamine), with no further oxidation observed past this product. The stoichiometry of the reaction was deduced to be IO 3- + 6H2NCH2CH2SH → I- + 3H2NCH2CH2S-SCH 2CH2NH2 + 3H2O in excess cysteamine conditions, whereas in excess iodate the stoichiometry of the reaction is 2IO3- + 10H2NCH2CH2SH → I2 + 5H2NCH2CH2S-SCH 2CH2NH2 + 6H2O. The stoichiometry of the oxidation of cysteamine by aqueous iodine was deduced to be I2 + 2H2NCH2CH2SH → 2I- + H 2NCH2CH2S-SCH2CH2NH 2 + 2H+. The bimolecular rate constant for the oxidation of cysteamine by iodine was experimentally evaluated as 2.7 (mol L -1)-1 s-1. The whole reaction scheme was satisfactorily modeled by a network of 14 elementary reactions.

Oxidation of aminothiols by molecular oxygen catalyzed by copper ions. Stoichiometry of the reaction

Catalysis of oxidation of aminothiols by copper ions was studied depending on the structure of aminothiols and pH of the medium. The catalytic reaction proceeds in the inner coordination sphere of Cu+. At pH 7-9, oxidation of bidentate aminothiols involves reduction of O2 to H 2O2. At pH 9-13, oxidation of chelating aminothiols is accompanied by reduction of O2 to H2O, whereas oxidation of weak-chelating aminothiols still proceeds by the former mechanism. In this process, the thiolate anions coordinated to the Cu+ ions lose one electron each and are oxidized to amino disulfides, which go from the inner sphere of the Cu+ complex into a solution. Procedures developed for the determination of amino disulfides, the chemiluminescence determination of H2O2 in the presence of aminothiols as luminescence quenchers, and a modified polarographic procedure for the determination of O2 allowed us to establish that oxidation of aminothiols is not accompanied by catalytic decomposition of H2O2 that formed.

Peroxidase-Catalyzed Chemiluminescence-Delay of Luminol for Determination of Traces of Copper(II)

Delayed chemilumunescence (CL) was observed in the copper(II)-catalyzed oxidation of cysteamine with oxygen in the presence of horseradish peroxidase (HRP) and luminol.After preferential catalytic oxidation of cysteamine by both Cu(II) and HRP, a HRP-catalyzed luminol CL reaction was subsequently commenced with hydrogen peroxide accumulated from the catalytic oxidation.Thus, a delay time from the reaction initiation to a sharp flash of CL was observed.The HRP-catalyzed CL-delay of luminol was applied to the determination of Cu(II).The delay time was linearly correlated with the Cu(II) concentration over the range from the detection limit of 5.0*10-9 to 1.5*10-5 M.The detection limit of the present method is a factor of 30 times better than that of the conventional luminol CL method.The relative standard deviation of the delay time in five succesive experiments was 3.2percent at 1.0*10-7 M of Cu(II).The present method was highly sensitive compared to the conventional luminol CL method.

Characterization of the nonheme iron center of cysteamine dioxygenase and its interaction with substrates

Cysteamine dioxygenase (ADO) has been reported to exhibit two distinct biological functions with a nonheme iron center. It catalyzes oxidation of both cysteamine in sulfur metabolism and N-terminal cysteine-containing proteins or peptides, such as regulator of G protein signaling 5 (RGS5). It thereby preserves oxygen homeostasis in a variety of physiological processes. However, little is known about its catalytic center and how it interacts with these two types of primary substrates in addition to O2. Here, using electron paramagnetic resonance (EPR), M?ssbauer, and UV-visible spectroscopies, we explored the binding mode of cysteamine and RGS5 to human and mouse ADO proteins in their physiologically relevant ferrous form. This characterization revealed that in the presence of nitric oxide as a spin probe and oxygen surrogate, both the small molecule and the peptide substrates coordinate the iron center with their free thiols in a monodentate binding mode, in sharp contrast to binding behaviors observed in other thiol dioxygenases. We observed a substrate-bound B-type dinitrosyl iron center complex in ADO, suggesting the possibility of dioxygen binding to the iron ion in a side-on mode. Moreover, we observed substrate-mediated reduction of the iron center from ferric to the ferrous oxidation state. Subsequent MS analysis indicated corresponding disulfide formation of the substrates, suggesting that the presence of the substrate could reactivate ADO to defend against oxidative stress. The findings of this work contribute to the understanding of the substrate interaction in ADO and fill a gap in our knowledge of the substrate specificity of thiol dioxygenases.

Detailed mechanistic investigation into the S-nitrosation of cysteamine

The nitrosation of cysteamine (H2NCH2CH 2SH) to produce cysteamine-S-nitrosothiol (CANO) was studied in slightly acidic medium by using nitrous acid prepared in situ. The stoichiometry of the reaction was H2NCH2CH2SH + HNO 2 → H2NCH2CH2SNO + H 2O. On prolonged standing, the nitrosothiol decomposed quantitatively to yield the disulfide, cystamine: 2H2NCH2CH 2SNO → H2NCH2CH2S-SCH 2CH2NH2 + 2NO. NO2 and N 2O3 are not the primary nitrosating agents, since their precursor (NO) was not detected during the nitrosation process. The reaction is first order in nitrous acid, thus implicating it as the major nitrosating agent in mildly acidic pH conditions. Acid catalyzes nitrosation after nitrous acid has saturated, implicating the protonated nitrous acid species, the nitrosonium cation (NO+) as a contributing nitrosating species in highly acidic environments. The acid catalysis at constant nitrous acid concentrations suggests that the nitrosonium cation nitrosates at a much higher rate than nitrous acid. Bimolecular rate constants for the nitrosation of cysteamine by nitrous acid and by the nitrosonium cation were deduced to be 17.9 ± 1.5 (mol/L)-1 s-1 and 6.7 ×104 (mol/L) -1 s-1, respectively. Both Cu(I) and Cu(II) ions were effective catalysts for the formation and decomposition of the cysteamine nitrosothiol. Cu(II) ions could catalyze the nitrosation of cysteamine in neutral conditions, whereas Cu(I) could only catalyze in acidic conditions. Transnitrosation kinetics of CANO with glutathione showed the formation of cystamine and the mixed disulfide with no formation of oxidized glutathione (GSSG). The nitrosation reaction was satisfactorily simulated by a simple reaction scheme involving eight reactions.

Fluorescein Chemiluminescence-Delay Method for the Determination of Ultratrace Amounts of Copper(II)

A delayed chemiluminescence (CL) was observed in the copper(II)-catalyzed oxidation of cysteamine with oxygen in the presence of fluorescein (FL) and horseradish peroxidase.The delayed CL reaction of FL was applied to the determination of Cu(II).The delay time was correlated linearly with Cu(II) concentration over the range from 5.0 * 10-9 M to 1.0 * 10-6 M.

A kinetic study of the oxidations of 2-mercaptoethanol and 2-mercaptoethylamine by heteropoly 11-tungsto-1- vanadophosphate in aqueous acidic medium

The kinetics of oxidation of 2-mercaptoethanol and 2-mercaptoethylamine by the heteropoly 11-tungsto-1- vanadophosphate anion, [PVVW11O40]4-, have been studied spectrophotometrically in aqueous perchloric acid at 25°C. EPR and optical studies show that [PVVW11O40]4- is reduced to the one-electron reduced heteropoly blue, [PVIVW11O40]5-, whilst the thiols are oxidized to the corresponding disulphides, RSSR. Spectrophotometric titrations show that the stoichiometry of both reactions is 1:1. At constant pH, the reactions show simple second-order kinetics with first-order dependence of rate on both [oxidant] and [thiol]. At constant [thiol], the rate of the reaction increases with increasing pH. Plots of kobs/[thiol]t versus 1/[H+] are linear with finite intercepts, showing that both the undissociated thiol (RSH) and thiolate ion (RS-) are reactive species. Generation of RS· from RSH proceeds via a separated-concerted proton-electron transfer mechanism. The reaction of thiolate ion is a simple outer-sphere electron transfer reaction. By applying the Marcus theory, the self-exchange rate constants for the couples HOCH2CH2S·/HOCH2CH2S- and H3N+CH2CH2S·/H3N+CH2CH2S- were evaluated as 3 × 109 and 2.2 × 108 M-1 s-1, respectively, at 25°C.

Self-Polymerization Promoting Monomers: In Situ Transformation of Disulfide-Linked Benzoxazines into the Thiazolidine Structure

Polybenzoxazines obtained especially from green synthons are facing challenges of the requirement of high ring-opening polymerization (ROP) temperature of the monomer, thus affecting their exploration at the industrial front. This demands effective structural changes in the monomer itself, to mediate catalyst-free polymerization at a low energy via one-step synthesis protocol. In this regard, monomers based on disulfide-linked bisbenzoxazine were successfully synthesized using cystamine (biobased) and cardanol (agro-waste)/phenol. Reduction of the disulfide bridge in the monomer using dithiothreitol under mild conditions in situ transformed the oxazine ring in the monomer, via neighboring group participation of the -SH group in a transient intermediate monomer, into a thiazolidine structure, which is otherwise difficult to synthesize. Structural transformation of ring-opening followed by the ring-closing intramolecular reaction led to an interconversion of O-CH2-N containing a six-membered oxazine ring to S-CH2-N containing a five-membered thiazolidine ring and a phenolic-OH. The structure of the monomer with the oxazine ring and its congener with the thiazolidine ring was characterized by spectroscopic methods and X-ray analysis. Kinetics of structural transformation at a molecular level is studied in detail, and it was found that the reaction proceeded via a transient 2-aminoethanethiol-linked benzoxazine intermediate, as supported by nuclear magnetic resonance spectroscopy and density functional theory studies. The thiazolidine-ring-containing monomer promotes ROP at a substantially low temperature than the reported mono-/bisoxazine monomers due to the dual mode of facilitation of the ROP reaction, both by phenolic-OH and by ring strain. Surprisingly, both the monomer structures led to the formation of a similar polymer structure, as supported by thermogravimetric analysis and Fourier transform infrared study. The current work highlights the benefits of inherent functionalities in naturally sourced feedstocks as biosynthons for the new latest generation of benzoxazine monomers.

Mechanistic scrutiny of the oxidations of thiol-containing drugs cysteamine and d-penicillamine by cis-diamminetetrachloroplatinum(IV)

Cysteamine (CA) and d-penicillamine (Pen) are the thiol-containing drugs and good antioxidants. Their reactions with a cisplatin Pt(IV) prodrug cis-diamminetetrachloroplatinum(IV) (cis-[Pt(NH3)2Cl4]) were investigated by use of rapid scan, stopped-flow, and mass spectral techniques. The kinetic traces are biphasic in nature, encompassing a faster reduction of cis-[Pt(NH3)2Cl4] to cisplatin followed by slow substitutions on cisplatin. The reduction reactions were demonstrated to follow overall second-order kinetics over a wide pH range. The observed second-order rate constants versus pH profiles were established at 25.0°C and 1.0?M ionic strength, indicating a huge increase of reaction rate with the increase of pH. However, the oxidations of CA and Pen by cis-[Pt(NH3)2Cl4] displayed different reaction stoichiometric ratios as revealed by the spectrophotometric titration experiments. Accordingly, CA was oxidized to CA-disulfide while Pen-sulfinic acid and Pen-disulfide were identified as the major products in the case of Pen via mass spectral analysis. The above similarities and differences are rationalized in terms of the proposed reaction mechanisms, which encompass similar rate-determining reactions for both CA and Pen, but involve disparate and faster followed-up reactions. Rate constants of the rate determining were derived at 25.0°C and 1.0?M ionic strength. A consequent species reactivity analysis revealed that the species -SCH2CH2NH3+ of CA and the species +H3NCH(COO?)CMe2S? of Pen played a predominant role toward the reduction of cis-[Pt(NH3)2Cl4] from pH 5 to 8, which also is a critical pH region for most of drugs.

Selective, Modular Probes for Thioredoxins Enabled by Rational Tuning of a Unique Disulfide Structure Motif

Specialized cellular networks of oxidoreductases coordinate the dithiol/disulfide-exchange reactions that control metabolism, protein regulation, and redox homeostasis. For probes to be selective for redox enzymes and effector proteins (nM to μM concentrations), they must also be able to resist non-specific triggering by the ca. 50 mM background of non-catalytic cellular monothiols. However, no such selective reduction-sensing systems have yet been established. Here, we used rational structural design to independently vary thermodynamic and kinetic aspects of disulfide stability, creating a series of unusual disulfide reduction trigger units designed for stability to monothiols. We integrated the motifs into modular series of fluorogenic probes that release and activate an arbitrary chemical cargo upon reduction, and compared their performance to that of the literature-known disulfides. The probes were comprehensively screened for biological stability and selectivity against a range of redox effector proteins and enzymes. This design process delivered the first disulfide probes with excellent stability to monothiols yet high selectivity for the key redox-Active protein effector, thioredoxin. We anticipate that further applications of these novel disulfide triggers will deliver unique probes targeting cellular thioredoxins. We also anticipate that further tuning following this design paradigm will enable redox probes for other important dithiol-manifold redox proteins, that will be useful in revealing the hitherto hidden dynamics of endogenous cellular redox systems.