542-78-9Relevant articles and documents
Azobispyrazole Family as Photoswitches Combining (Near-) Quantitative Bidirectional Isomerization and Widely Tunable Thermal Half-Lives from Hours to Years**
He, Yixin,Li, Tao,Shangguan, Zhichun,Xie, Mingchen,Yu, Chunyang,Zhang, Zhao-Yang
, p. 16539 - 16546 (2021)
Azobenzenes are classical molecular photoswitches that have been widely used. In recent endeavors of molecular design, replacing one or both phenyl rings with heteroaromatic rings has emerged as a strategy to expand molecular diversity and access improved photoswitching properties. Many mono-heteroaryl azo molecules with unique structures and/or properties have been developed, but the potential of bis-heteroaryl architectures is far from fully exploited. We report a family of azobispyrazoles, which combine (near-)quantitative bidirectional photoconversion and widely tunable Z-isomer thermal half-lives from hours to years. The two five-membered rings remarkably weaken the intramolecular steric hindrance, providing new possibilities for engineering the geometric and electronic structure of azo photoswitches. Azobispyrazoles generally exhibit twisted Z-isomers that facilitate complete Z→E photoisomerization, and their thermal stability can be broadly adjusted regardless of the twisted shape, overcoming the conflict between photoconversion (favored by the twisted shape) and Z-isomer stability (favored by the orthogonal shape) encountered by mono-heteroaryl azo switches.
Synthesis, structural studies and stability of model cysteine containing DNA-protein cross-links
Salus, Kinga,Hoffmann, Marcin,Siod?a, Tomasz,Wyrzykiewicz, Bo?ena,Pluskota-Karwatka, Donata
, p. 2409 - 2424 (2017)
DNA-protein cross-links (DPCs) are bulky, helix-distorting lesions that are formed upon irreversible bonding of proteins to chromosomal DNA in the presence of cross-linking agents. Among a broad range of such agents are α,β-unsaturated carbonyl compounds, which act essentially as bifunctional alkylating agents and form adducts with DNA bases. These adducts can further undergo interactions with other cellular macromolecules leading to the formation of cross-linked products. We synthesized and structurally characterized N-acetylcysteine cross-links formed in the reactions with aldehydic adducts of adenine nucleosides, which possess enol functionality and represent model α,β-unsaturated carbonyl systems. Studies performed by the use of NMR spectroscopy, DFT and ab initio methods established that two of these cross-links exist as rotamers stable at room temperature. Application of Atoms in Molecules Theory enabled hydrogen bonding and other stabilizing interactions within the studied molecules to be estimated. Under physiological conditions the cross-links were found to be relatively stable until Nα-acetyllysine was present in the reaction medium. The presence of this amino acid caused fast transformation of the N-acetylcysteine cross-links into a range of their lysine derivatives. Although instability of the cysteine adduct with acrolein was reported, we showed that the mechanism involved in the gradual decomposition of the N-acetylcysteine cross-links differs from that proposed for acrolein adduct degradation. This demonstrates that in spite of similarities in their structures, numerous α,β-unsaturated carbonyl compounds can interact with nucleophilic biomolecules by different mechanisms leading to structural heterogeneity of the resulting products. Our findings provide an explanation for difficulties in identifying the cysteine containing DPCs in vivo and in vitro, and may be of great importance with respect to detection and isolation of such lesions from biological materials.
Structural studies of malonaldehyde-glyoxal and malonaldehyde-methylglyoxal etheno adducts of adenine nucleosides based on spectroscopic methods and DFT-GIAO calculations
Salus, Kinga,Hoffmann, Marcin,Wyrzykiewicz, Bozena,Pluskota-Karwatka, Donata
, p. 3875 - 3884 (2016)
Etheno adducts are formed in the reactions of DNA bases with chloroacetaldehyde, with lipid peroxidation products, and also with metabolites of vinyl chloride and furan. The presence of such modifications in the genetic material may lead to errors in replication with consequences of mutations and even carcinogenesis. For an understanding of the biological significance of etheno adducts it is important to determine their structures. Structural identification is also essential for using these adducts as inflammatory or cancer biomarkers. This paper reports structural studies on two adducts formed in the reactions of malonaldehyde and glyoxal with adenosine (M1Gx-A), and malonaldehyde and methylglyoxal with 2′-deoxyadenosine (M1MGx-dA). NMR spectroscopy and theoretical methods have been used. DFT-GIAO calculations were performed at M06/6-311++G(2df,2pd), B3LYP/6-311++G(2df,2pd) and M06/6-31++G(d,p) levels both in the gas phase and taking into account the effect of solvents (water, methanol and DMSO) using PCM approximation. It has been shown that when M06 or B3LYP functionals with the 6-311++G(2df,2pd) basis set are used, 1H NMR chemical shifts very close to experimental values are obtained and that the results of GIAO calculations at the M06/6-31++G(d,p) level have a better correlation with measured 13C NMR chemical shift values. PCM improves the correlation of results in both cases.
Modification of casein by the lipid oxidation product malondialdehyde
Adams, An,De Kimpe, Norbert,Van Boekel, Martinus A. J. S.
, p. 1713 - 1719 (2008)
The reaction of malondialdehyde with casein was studied in aqueous solution to evaluate the impact of this lipid oxidation product on food protein modification. By using multiresponse modeling, a kinetic model was developed for this reaction. The influence of temperature and pH on protein browning and malondialdehyde degradation was evaluated. The hypothesis that one malondialdehyde unit leads to the cross-linking of two casein-bound lysine residues was in accordance with the data. At higher malondialdehyde concentrations, a different reaction mechanism was operative, probably involving a dihydropyridine cross-link. The results obtained were compared with the reaction of casein with 2-oxopropanal, a well-studied α-dicarbonyl compound. The reaction of casein with 2-oxopropanal followed a different reaction pathway. Comparison of the degree of browning of casein by reaction with malondialdehyde and 2-oxopropanal showed a considerably higher degree of browning induced by malondialdehyde. This research has shown that kinetic modeling is a useful tool to unravel reaction mechanisms. Clearly, the contribution of lipid oxidation products, such as malondialdehyde, to protein modification (both in food and in vivo) can be substantial and needs to be taken into account in future studies.
A novel fluorescent malondialdehyde-lysine adduct
Itakura, Koichi,Uchida, Koji,Osawa, Toshihiko
, p. 75 - 79 (1996)
We report a novel type of fluorescent product derived from the reaction of the lysine residue with malondialdehyde (MDA). When the lysine-containing peptide (N-acetyl-glycyl-L-lysine methyl ester) was treated with MDA prepared by the acid hydrolysis of 1,1,3,3-tetramethoxypropane, the main fluorescent product, which corresponded neither to the 1-amino-3-iminopropene derivative (2) nor to the 4-methyl-1,4-dihydro-3,5-dicarbaldehyde derivative (3), was detected by reverse-phase HPLC. By analysis of its UV NMR, and high-resolution FAB mass spectra, it was confirmed to be 1-[5-carboxymethyl-5-(N-acetylglycylamino)pentyl]-3-[1-5-carboxymethyl-5 -acetylglycylamino)-pentyl)-3,5-diformyl-1,4-dihydropyridin-4-yl] pyridinium (1). This finding may provide a new clue to the formation mechanisms of fluorescent lipofuscin-like pigment.
Identification of fluorescent 2′-deoxyadenosine adducts formed in reactions of conjugates of malonaldehyde and acetaldehyde, and of malonaldehyde and formaldehyde
Curieux, Frank Le,Pluskota, Donata,Munter, Tony,Sjoeholm, Rainer,Kronberg, Leif
, p. 1228 - 1234 (2000)
2′-Deoxyadenosine was reacted with malonaldehyde in the presence of formaldehyde or acetaldehyde. The reactions were carried out at 37 °C in aqueous solution at acidic conditions. The reaction mixtures were analyzed by HPLC. In both reactions, two major products were formed. The reaction products were isolated and purified by C18 chromatography, and their structures were characterized by UV absorbance, fluorescence emission, 1H and 13C NMR spectroscopy, and mass spectrometry. The reaction products isolated from the mixture containing formaldehyde, malonaldchyde, and deoxyadenosine were identified as 3-(2′-deoxy-β-D-ribofuranosyl)-7H-8-formyl[2,1-i]pyrimidopurine (M1FA-dA) and 9-(2′-deoxy-β-D-ribofuranosyl)-6-(3,5-diformyl-l,4-dihydro-1-pyrid yl)purine (M2FA-dA). In the reaction mixture consisting of acetaldehyde, malonaldehyde, and deoxyadenosine, the identities of the products were determined to be 3-(2′-deoxy-β-D-ribofuranosyl)-7-methyl-8-formyl[2,1-i]pyrimidopur ine (M1-AA-dA) and 9-(2′-deoxy-β-D-ribofuranosyl)-6-(3,5-diformyl-4-methyl-1,4-dihydr o-1-pyridyl)purine (M2AA-dA). The yields of the compounds were 1.8 and 0.7% for M1FA-dA and M2FA-dA, respectively, and 6.8 and 10% for M1AA-dA and M2AA-dA, respectively. All compounds exhibited marked fluorescent properties. These findings show that in addition to direct reaction of a specific aldehyde with 2′-deoxyadenosine, aldehyde conjugates also may react with the base. Although three of the adducts (M1FA-dA, M2FA-dA, and M1AA-dA) could not be detected in reactions carried out under neutral conditions, the possibility that trace amounts of the adducts may be formed under physiological conditions cannot be ruled out. Therefore, conjugate adducts must be considered in work that aims at clarifying the mechanism of aldehyde genotoxicity.
Luminol chemiluminescence and peroxidation of unsaturated fatty acid induced by the xanthine oxidase system: effect of oxygen radical scavengers.
Miura,Ogiso
, p. 3402 - 3407 (1985)
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Development of a selective ESI-MS derivatization reagent: Synthesis and optimization for the analysis of aldehydes in biological mixtures
Eggink, Mark,Wijtmans, Maikel,Ekkebus, Reggy,Lingeman, Henk,De Esch, Iwan J. P.,Kool, Jeroen,Niessen, Wilfried M. A.,Irth, Hubertus
, p. 9042 - 9051 (2008)
In LC-MS, derivatization is primarily used to improve ionization characteristics, especially for analytes that are not (efficiently) ionized by ESI or APCI such as aldehydes, sugars, and steroids. Derivatization strategies are then directed at the incorporation of a group with a permanent charge. A compound class that typically requires derivatization prior to LC-MS is the group of small aliphatic aldehydes that are, for instance, analyzed as the key biomarkers for lipid peroxidation in organisms. Here we report the development of a new tailor-made, highly sensitive, and selective derivatization agent 4-(2-(trimethylammonio)ethoxy)benzenaminium halide (4-APC) for the quantification of aldehydes in biological matrixes with positive ESI-MS/MS without additional extraction procedures. 4-APC possesses an aniline moiety for a fast selective reaction with aliphatic aldehydes as well as a quaternary ammonium group for improved MS sensitivity. The derivatization reaction is a convenient one-pot reaction at a mild pH (5.7) and temperature (10°C). As a result, an in-vial derivatization can be performed before analysis with an LC-MS/MS system. All aldehydes are derivatized within 30 min to a plateau, except malondialdehyde, which requires 300 min to reach a plateau. All derivatized aldehydes are stable for at least 35 h. Linearity was established between 10 and 500 nM and the limits of detection were in the 3-33 nM range for the aldehyde derivatives. Furthermore, the chosen design of these structures allows tandem MS to be used to monitor the typical losses of 59 and 87 from aldehyde derivatives, thereby enabling screening for aldehydes. Finally, of all aldehydes, pentanal and hexanal were detected at elevated levels in pooled healthy human urine samples.
A purified MAA-based ELISA is a useful tool for determining anti-MAA antibody titer with high sensitivity
Shimomoto, Takasumi,Collins, Leonard B.,Yi, Xianwen,Holley, Darcy W.,Zhang, Zhenfa,Tian, Xu,Uchida, Koji,Wang, Chunguang,H?rkk?, Sohvi,Willis, Monte S.,Gold, Avram,Bultman, Scott J.,Nakamura, Jun
, (2017)
Atherosclerosis is widely accepted to be a chronic inflammatory disease, and the immunological response to the accumulation of LDL is believed to play a critical role in the development of this disease. 1,4-Dihydropyridine-type MAA-adducted LDL has been implicated in atherosclerosis. Here, we have demonstrated that pure MAA-modified residues can be chemically conjugated to large proteins without by-product contamination. Using this pure antigen, we established a purified MAA-ELISA, with which a marked increase in anti-MAA antibody titer was determined at a very early stage of atherosclerosis in 3-month ApoE-/-mice fed with a normal diet. Our methods of N? -MAA-L-lysine purification and purified antigen-based ELISA will be easily applicable for biomarker-based detection of early stage atherosclerosis in patients, as well as for the development of an adduct-specific Liquid Chromatography/Mass Spectrometry-based quantification of physiological and pathological levels of MAA.
2-methyl nicotinate as well as preparation method and application thereof
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Paragraph 0114-0119; 0125-0130; 0137-0142, (2021/05/22)
The invention relates to 2-methyl nicotinate as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) reacting 1, 1, 3, 3-tetramethoxypropane or 1, 1, 3, 3-tetraethoxypropane under the action of acid to obtain a compound B; (2) reacting the compound B and beta-aminocrotonate in a first organic solvent to obtain 2-methyl nicotinate, wherein no foul acrolein is used in the process, the safety coefficient of production is effectively improved, the reaction raw materials are easy to obtain, the conditions are mild, the operation is simple, the yield is greater than 65%, the product purity reaches 98% or above, and the method is suitable for industrial production and has a wide application prospect. The obtained product can be used as an intermediate for synthesizing 2-methyl nicotinic acid, and can be used for synthesizing medicines.
Preparation method of 3-thiophenecarboxaldehyde
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Page/Page column 6-8, (2018/06/15)
The invention relates to the technical field of organic synthesis, in particular to a preparation method of 3-thiophenecarboxaldehyde. The preparation method of 3-thiophenecarboxaldehyde comprises thefollowing steps: performing reaction on 1,1,3,3-tetramethoxypropane under the acidic condition, performing mixed reaction on the reaction product and 1,4-dithio-2,5-diol under the alkaline conditionand performing aftertreatment to obtain the 3-thiophenecarboxaldehyde. By the preparation method of 3-thiophenecarboxaldehyde, the 3-thiophenecarboxaldehyde product with the purity exceeding 98 percent can be prepared only through simple mixing and stirring reaction, reaction does not need ultralow temperature and dangerous reagents in the preparation process, and the production safety coefficientis increased. Furthermore, the preparation method provided by the invention is simple in operation, the raw materials are easily available, operation cost and raw material cost are reduced, and the preparation method is suitable for industrialized production of 3-thiophenecarboxaldehyde.
