15441-06-2Relevant academic research and scientific papers
Modulating Thiol p Ka Promotes Disulfide Formation at Physiological pH: An Elegant Strategy to Design Disulfide Cross-Linked Hyaluronic Acid Hydrogels
Bermejo-Velasco, Daniel,Azémar, Alice,Oommen, Oommen P.,Hilborn, J?ns,Varghese, Oommen P.
, p. 1412 - 1420 (2019)
The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors, and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants, and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as l-cysteine indicated disulfide formation at a 2.8-fold higher (k1 = 5.04 × 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid (k1 = 1.80 × 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-l-cysteine substrate (k1 = 0.51 × 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the pKa value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the pKa of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys); and 8.1 for HA-thiol (HA-SH) derivatives, respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 min or 10 h, respectively, at pH 7.4. After completion of cross-linking reaction, both gels demonstrated a storage modulus G′ ≈ 3300-3500 Pa, which indicated comparable levels of cross-linking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.
Polymeric and dendrimeric pyridoxal enzyme mimics
Liu, Lei,Breslow, Ronald
, p. 3277 - 3287 (2004)
Pyridoxal was covalently attached to polyethylenimine polymers, but the resulting materials were found to degrade rapidly. In comparison, the dendrimeric pyridoxals, which possess only one pyridoxal unit at the core of every dendrimer molecule were found to be relatively stable compounds. A total of 12 poly(amidoamine) type dendrimers were synthesized. They range from G1 to G6 with either NMe2 or NHAc termini. The NMe2-terminated pyridoxal dendrimers racemize α-amino acids 50-100 times faster than does simple pyridoxal, while the NHAc-terminated pyridoxal dendrimers racemize α-amino acids only 3-5 times faster than does simple pyridoxal. Both the NMe2- and NHAc-terminated pyridoxal dendrimers decarboxylate 2-amino-2-phenyl-propionic acid 1-3 times faster than simple pyridoxal. The interior polarity in the pyridoxal dendrimers is similar to that of 85:15 water-DMF solution. Furthermore, we successfully incorporated eight lauryl groups to the G5 pyridoxal dendrimer at known positions. The laurylated dendrimer exhibits lower racemization and decarboxylation rates than do the unlaurylated ones, in contrast to the positive rate effects of laurylation in polyethylenimine-pyridoxamines in our previous transamination studies.
Vancomycin disulfide derivatives as antibacterial agents
Mu, YongQi,Nodwell, Matthew,Pace, John L.,Shaw, Jeng-Pyng,Judice, J. Kevin
, p. 735 - 738 (2004)
A series of lipidated vancomycin analogues 1 bearing disulfide bonds within their lipid chains was designed and synthesized to optimize their ADME profiles while retaining antibacterial potency. These compounds exhibited good activity against resistant organisms and low accumulation in tissues such as kidney and liver.
Green Aerobic Oxidation of Thiols to Disulfides by Flavin-Iodine Coupled Organocatalysis
Iida, Hiroki,Kozako, Ryo,Oka, Marina
supporting information, p. 1227 - 1230 (2021/06/21)
Coupled catalysis using a riboflavin-derived organocatalyst and molecular iodine successfully promoted the aerobic oxidation of thiols to disulfides under metal-free mild conditions. The activation of molecular oxygen occurred smoothly at room temperature through the transfer of electrons from the iodine catalyst to the biomimetic flavin catalyst, forming the basis for a green oxidative synthesis of disulfides from thiols.
Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents
Chhalodia, Anuj Kumar,Dickschat, Jeroen S.
, p. 569 - 580 (2021/03/31)
Two analogues of 3-(dimethylsulfonio)propanoate (DMSP), 3-(diallylsulfonio)propanoate (DAllSP), and 3-(allylmethyl-sulfonio)propanoate (AllMSP), were synthesized and fed to marine bacteria from the Roseobacter clade. These bacteria are able to degrade DMSP into dimethyl sulfide and methanethiol. The DMSP analogues were also degraded, resulting in the release of allylated sulfur volatiles known from garlic. For unknown compounds, structural suggestions were made based on their mass spectrometric fragmentation pattern and confirmed by the synthesis of reference compounds. The results of the feeding experiments allowed to conclude on the substrate tolerance of DMSP degrading enzymes in marine bacteria.
Forging C?S(Se) Bonds by Nickel-catalyzed Decarbonylation of Carboxylic Acid and Cleavage of Aryl Dichalcogenides
Zhou, Jing-Ya,Zhu, Yong-Ming
, p. 2452 - 2461 (2021/06/28)
A nickel-catalyzed decarbonylation of carboxylic acids cross-coupling protocol has been developed for the straightforward C?S(Se) bond formation. This reaction is promoted by a commercially-available, user-friendly, inexpensive, air and moisture-stable nickel precatalyst. Various carboxylic acids and a wide range of aryl dichalcogenide substrates were tolerated in this process which afforded products in good to excellent yields. In addition, the present reaction can be conducted on gram scale in good yield.
Method and device for continuously producing thiopropionate series compounds through pipeline type
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Paragraph 0085; 0087; 0095; 0097-0099, (2021/11/27)
The invention discloses a method and a device for continuously producing thiopropionate series compounds through pipeline type, and can simultaneously or separately prepare thiodipropionate compounds. Dithionate type compounds and mercapto ester compounds. The method is simple to operate, low in cost and high in yield, and is suitable for industrial production.
Cyclic telluride reagents with remarkable glutathione peroxidase-like activity for purification-free synthesis of highly pure organodisulfides
Arai, Kenta,Osaka, Yuui,Haneda, Masahiro,Sato, Yuumi
, p. 3647 - 3655 (2019/07/22)
Monoamino cyclic tellurides with a five- or six-membered ring structure and their derivatives were developed as a new class of catalyst for the oxidation of organothiols to organodisulfides in a glutathione peroxidase-like catalytic reaction. Quantitative conversion and high reaction rate were achieved by performing the reaction in an organic-aqueous segmented microflow system. Importantly, the process circumvented product purification, which is a major limitation of current organodisulfide synthetic methods.
Unsymmetrical Disulfide Synthesis through Photoredox Catalysis
Dethe, Dattatraya H.,Srivastava, Aparna,Dherange, Balu D.,Kumar, B. Vijay
supporting information, p. 3020 - 3025 (2018/08/23)
A facile and eco-friendly visible light-mediated synthesis of symmetrical and unsymmetrical disulfides using tris[2-phenylpyridinato-C2,N]iridium(III) under additive and oxidant free conditions has been disclosed. The developed method is very mild, several functional group tolerant and highly atom economical requiring extremely low amount of catalyst loading (0.5 mol%). (Figure presented.).
One-pot synthesis of 4, 5 - dichloro - 2 - isothiazolinone process
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Paragraph 0036; 0037; 0038, (2017/08/25)
The invention discloses a process for synthesizing 4,5-dichloro-2-methylisothiazolinone by a one-pot method. The process comprises the following steps: mixing methyl acrylate, a methylamine aqueous solution and sulfur to obtain a mixture, introducing hydrogen sulfide gas into the mixture to generate a dimethyl 3,3'-dithiobispropionate crude product; and then, on the basis of the dimethyl 3,3'-dithiobispropionate crude product, introducing methylamine gas to synthesize N, N'-dimethyl-3,3`- dithiodipropionamide, thereby obtaining the product 4,5-dichloro-2-methylisothiazolinone by reacting chlorine gas with the N, N'-dimethyl-3,3- dithiodipropionamide. According to the method provided by the invention, the technical process is simplified, the operation cost is reduced, and wastewater generation amount is greatly reduced; and three steps of carrying out Michael addition reaction, amidation and chlorination can be carried out in the same reaction kettle, so that separating and purifying processes of an intermediate product are reduced, and therefore, the equipment investment is low, and the obtained product is high in purity.
