1073-23-0Relevant academic research and scientific papers
Stable and rigid DTPA-like paramagnetic tags suitable for in vitro and in situ protein NMR analysis
Chen, Jia-Liang,Zhao, Yu,Gong, Yan-Jun,Pan, Bin-Bin,Wang, Xiao,Su, Xun-Cheng
, p. 77 - 92 (2018)
Organic synthesis of a ligand with high binding affinities for paramagnetic lanthanide ions is an effective way of generating paramagnetic effects on proteins. These paramagnetic effects manifested in high-resolution NMR spectroscopy are valuable dynamic and structural restraints of proteins and protein–ligand complexes. A paramagnetic tag generally contains a metal chelating moiety and a reactive group for protein modification. Herein we report two new DTPA-like tags, 4PS-PyDTTA and 4PS-6M-PyDTTA that can be site-specifically attached to a protein with a stable thioether bond. Both protein-tag adducts form stable lanthanide complexes, of which the binding affinities and paramagnetic tensors are tunable with respect to the 6-methyl group in pyridine. Paramagnetic relaxation enhancement (PRE) effects of Gd(III) complex on protein-tag adducts were evaluated in comparison with pseudocontact shift (PCS), and the results indicated that both 4PS-PyDTTA and 4PS-6M-PyDTTA tags are rigid and present high-quality PREs that are crucially important in elucidation of the dynamics and interactions of proteins and protein-ligand complexes. We also show that these two tags are suitable for in-situ protein NMR analysis.
Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-Heteroarylthiomethyldipyridodiazepinone derivatives
Yoakim,Bonneau,Deziel,Doyon,Duan,Guse,Landry,Malenfant,Naud,Ogilvie,O'Meara,Plante,Simoneau,Thavonekham,Boes,Cordingley
, p. 739 - 742 (2004)
A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor metabolic stability in rat liver microsomes.
Electronic influence of substitution on the pyridine ring within NNN pincer-type molecules
Burnett, Marianne E.,Green, Kayla N.,Schwartz, Timothy M.
, p. 2356 - 2363 (2020)
Pincer molecules are of increasing interest due to the modular nature of modification and range of reactivity observed when coordinated to metal ions. A subset within the family of pincer molecules use a pyridine group to bridge the outer two arms as well as provide a N-donor atom for metal binding. While the arm appendages have been studied extensively, little research has been conducted on the electronic effects of the central, substituted pyridine systems. Therefore, a series of NNN pincer-type ligands with substitution on the 4-position of the pyridine ring with -OH, -OBn, -H, -Cl, and -NO2 functional groups were synthesized and characterized through NMR spectroscopy and ESI-HRMS. Each pincer was metalated with Cu(ii) salts and evaluated through X-ray diffraction analysis, cyclic voltammetry, and density functional theory analysis. The results indicate that the relatively unstudied -OBn group demonstrates both electron-withdrawing (XRD bond lengths) and electron-donating (NMR spectroscopy) properties. The -NO2 pincer ligand shows a redox event within experimental windows evaluated, in contrast to the other congeners studied. In addition, electron-donating groups increase the electron density around the Cu(ii) center based on DFT studies and cyclic voltammetry. These findings can be applied to other pyridine-based pincer systems when considering ligand design and warrants future characterization of 4-position substituted pyridines.
N-oxidation of 2-substituted pyridines and quinolines by dimethyldioxirane: Kinetics and steric effects
Winkeljohn, W. Rucks,Leggett-Robinson, Pamela,Peets, Monique R.,Strekowski, Lucjan,Vasquez, Pedro C.,Baumstark
, p. 25 - 28 (2007)
The oxidation of 2-substituted pyridines and selected N-containing aromatic heterocycles by dimethyldioxirane (1) produced the corresponding N-oxides as the sole products, quantitatively in most cases. The second order rate constants for N-oxidation by 1 in dried acetone at 23°C were determined for a series of 2-substituted pyridines 2-10, quinolines 11-14 and isoquinolines 15,16. An excellent correlation of log k2 with Taft (σ*) constants was obtained for 2-substituted pyridines (R = Me, Et, Prn, Pr i, 3-pentyl) with the exception of the data for 2-f-butylpyridine. The results for the substituted quinolines and isoquinolines followed the same trends observed with the pyridines. Steric effects due to 2-substitution and periinteractions can substantially reduce reactivity. The results provide insights into the geometrical requirements for N-oxidation by dimethyldioxirane.
Kinetic assay of the michael addition-like thiol-ene reaction and insight into protein bioconjugation
Ma, Fei-He,Chen, Jia-Liang,Li, Qing-Feng,Zuo, Hui-Hui,Huang, Feng,Su, Xun-Cheng
, p. 1808 - 1816 (2014)
The chemical modification of proteins is a valuable technique in understanding the functions, interactions, and dynamics of proteins. Reactivity and selectivity are key issues in current chemical modification of proteins. The Michael addition-like thiol-ene reaction is a useful tool that can be used to tag proteins with high selectivity for the solvent-exposed thiol groups of proteins. To obtain insight into the bioconjugation of proteins with this method, a kinetic analysis was performed. New vinyl-substituted pyridine derivatives were designed and synthesized. The reactivity of these vinyl tags with L-cysteine was evaluated by UV absorption and high-resolution NMR spectroscopy. The results show that protonation of pyridine plays a key role in the overall reaction rates. The kinetic parameters were assessed in protein modification. The different reactivities of these vinyl tags with solvent-exposed cysteine is valuable information in the selective labeling of proteins with multiple functional groups. Tag! You're it! The Michael addition-like thiol-ene reaction between a pyridine-substituted vinyl group and the thiol of L-cysteine is evaluated by kinetic assay. Diverse reaction rates between different vinyl tags and free thiols are assessed, and the determined reactivity offers valuable information on protein bioconjugation.
Single-armed phenylsulfonated pyridine derivative of DOTA is rigid and stable paramagnetic tag in protein analysis
Yang, Feng,Wang, Xiao,Pan, Bin-Bin,Su, Xun-Cheng
, p. 11535 - 11538 (2016)
Single-armed DOTA-like phenylsulfonated pyridine derivatives are rigid and stable paramagnetic tags for site-specific labeling of proteins. Their reactions with a solvent-exposed protein thiol group generate a stable C-S bond and produce one single paramagnetic species in solution NMR. The generated large paramagnetic effects yield valuable long-range structural restraints for proteins.
The oxidation of pyridines catalyzed by surfactant-encapsulated polyoxometalate [(C18H37)2(CH3) 2N]8[HBW11O39] with the temperature-responsive property of solubility
Zhao, Wei,Yang, Chunxia,Ding, Yong,Ma, Baochun
, p. 2614 - 2618 (2013)
Temperature-responsive characterization of solubility based on a surfactant-encapsulated polyoxometalate ([(C18H37) 2(CH3)2N]8[HBW11O 39]) in tert-butyl alcohol was described and used in catalytic oxidation of pyridines. The catalyst could be recovered and reused several times by controlling the temperature.
Effect of intermolecular = C-H···O interaction on the crystal structure and vibrational properties of 2,6-dimethyl-4-nitropyridine N-oxide
Hanuza,MacZka,Waskowska,Oganowski,Ban-Oganowska,Lutz,Van Der Maas
, p. 201 - 212 (1998)
The crystal structure of 2,6-dimethyl-4-nitropyridine N-oxide (DMNPO) has been determined at ambient temperature. The compound crystallizes as a monoclinic structure, space group P2/n, with 12 molecules per unit cell. The unit cell contains three non-equivalent formula units. The nitro group is not coplanar with the pyridine ring. Through a system of =C-H···O hydrogen bonds the molecules are arranged into a two-dimensional network of layers parallel to the axc plane. The IR and Raman spectra, measured in the 3500-100 cm-1 region at ambient temperature, are correlated with X-ray structural data. The assignment of IR and Raman bands is given. The appearance of characteristic vibrational features in the spectra of this compound and the observed shifts of the =C-H and N-O IR active stretching modes, when the sample is dissolved in CCl4, is discussed in terms of the relatively strong =C-H···O hydrogen bonds present in this crystal.
Method for preparing sulfone and N-oxygen compound by using green and efficient oxidation system
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Paragraph 0045-0047, (2021/01/29)
The invention discloses a method for preparing sulfone and N-oxygen compound by using a green and efficient oxidation system. The method comprises the following steps of: by using a tertiary amine compound or aromatic thioether or fatty thioether compound as a raw material, H2O2 as an oxidant, methanol as a reaction solvent and potassium carbonate as an alkali, introducing sulfuryl fluoride 5O2F2gas as an accelerator; performing stirring at room temperature under a sealed condition for oxidation reaction; and after finishing the reaction, filtering to remove solid potassium carbonate, dryingto remove water, filtering to obtain a crude product, and finally carrying out column chromatography separation to obtain a pure product. Tertiary amine is oxidized into an N-oxygen compound, and thethioether is oxidized into sulfone. According to the method, the sulfuryl fluoride (SO2F2) which is very cheap and easy to obtain is used as the reaction promoter, green and environment-friendly hydrogen peroxide (H2O2) is used as an oxidizing agent, and so that the yield of the reaction is generally high; after the reaction, byproducts are only water and inorganic salts (SO4 and F) whichare easy to remove and free of pollution, and the green and efficient oxidation system can be realized, and therefore, the method is suitable for large-scale industrial production.
SO2F2-mediated oxidation of primary and tertiary amines with 30% aqueous H2O2 solution
Liao, Xudong,Zhou, Yi,Ai, Chengmei,Ye, Cuijiao,Chen, Guanghui,Yan, Zhaohua,Lin, Sen
supporting information, (2021/11/01)
A highly efficient and selective oxidation of primary and tertiary amines employing SO2F2/H2O2/base system was described. Anilines were converted to the corresponding azoxybenzenes, while primary benzylamines were transformed into nitriles and secondary benzylamines were rearranged to amides. For tertiary amine substrates quinolines, isoquinolines and pyridines, their oxidation products were the corresponding N-oxides. The reaction conditions are very mild and just involve SO2F2, amines, 30% aqueous H2O2 solution, and inorganic base at room temperature. One unique advantage is that this oxidation system is just composed of inexpensive inorganic compounds without the use of any metal and organic compounds.
