Ultra-trace determination of S-nitrosothiols in blood samples by spectrofluorimetry with 8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene

Increasing evidence suggests that S-nitrosothiols (RSNO) may represent naturally occurring nitric oxide (NO) surrogates and function as intermediates in NO metabolism. In this work, a simple, sensitive, and selective micromethod is developed and validated for quantification of RSNO. A fluorescent probe 8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacence (DABODIPY) is firstly used to label RSNO. The derivatization reaction is performed in aqueous medium at 30 degrees C for 15min in the presence of 6x10(-5)molL(-1)Hg2+ and the derivative is detected by fluorescence at lambda(ex)/lambda(em)=500/510nm. A linear function of concentration in the range of (2.0-600.0)x10(-8)molL(-1) is observed with a correlation coefficient of 0.9992 and detection limit of 1.2x10(-9)molL(-1) (S/N=3). This technique has been successfully applied to quantify RSNO in some human blood samples including healthy persons and patients suffering from cardiovascular diseases.     

Simultaneous Quantification of Seven Main Triterpenoid Saponins in Radix et Rhizoma Clematidis by LC–ELSD

Chinese clematis is a Chinese medicine with anti-inflammatory and anti-rheumatoid properties. Studies showed the triterpenoid saponins of this herb represent the major active components with therapeutic activities for the treatment of inflammatory diseases. The LC–ELSD method was developed to quantitatively analyze seven major triterpenoid saponins in 22 samples from different habitats. The linearity, sensitivity, precision, and accuracy were investigated. It showed the great variation of the contents of each saponin. We concluded clematichinenoside AR is the major saponin in all the samples. This method can be used to effectively evaluate and monitor the quality of Chinese clematis in clinical use.     

CeO2对低氟连铸保护渣转折温度和结晶性能的影响

研究了低氟条件下,稀土氧化物CeO2对连铸保护渣转折温度和结晶性能的影响,同时与常规的高氟连铸保护渣性能进行了对比分析。结果表明：在碱度R较低的条件下,随着CeO2含量的升高,转折温度和结晶温度均有先下降后上升的趋势;在碱度较高的情况下,CeO2的加入将明显提高连铸保护渣的转折温度和凝固温度。     

Synthesis and biological evaluation of novel piperidin-4-ol derivatives

Abstract  

A series of novel piperidin-4-ol derivatives were designed, synthesized, and evaluated for potential treatment of HIV. The compounds were obtained via an efficient synthetic route in excellent yields and have been characterized by ¹H NMR, ¹³C NMR, MS, and elemental analysis. The CCR5 antagonistic activities of the compounds have also been evaluated.     

A photoactive isoprenoid diphosphate analogue containing a stable phosphonate linkage: synthesis and biochemical studies with prenyltransferases

A number of biochemical processes rely on isoprenoids, including the post-translational modification of signaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross-linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyl diphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics, photolabeling experiments, as well as X-ray crystallographic analysis with a protein prenyltransferase are described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this new analogue was explored by using it to photoaffinity label crude protein extracts obtained from Hevea brasiliensis latex. Those experiments suggest that a small protein, rubber elongation factor, interacts directly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as a substrate.     

Simultaneous determination of pantoprazole and its two metabolites in dog plasma by HPLC

A simple and sensitive high-performance liquid chromatography (HPLC) method is developed and validated for simultaneous determination of pantoprazole and its two metabolites (pantoprazole sulfone and pantoprazole thioether) in dog plasma and applied to a pharmacokinetic study in Beagle dogs. Following a protein precipitation procedure, the samples are separated using reversed-phase HPLC (C18) by a gradient of acetonitrile and ammonium acetate (pH 6.0) at a flow rate of 1.0 mL/min and quantitated using UV detection at 290 nm. Omeprazole is selected as the internal standard. The method has a lower limit of quantitation of 0.025 microg/mL for pantoprazole and its two metabolites, using 0.1-mL aliquots of plasma. The linear calibration curves are obtained in the concentration range of 0.025-10.0 microg/mL for three analytes. The intra- and interrun precision (relative standard deviation), calculated from quality control (QC) samples, is less than 13% for three analytes. The accuracy determined from QC samples is between -6.4% and 12%.     

Dissociation mechanism of 2-propanol on a Si(111)-(7x7) surface studied by scanning tunneling microscopy

Adsorption of 2-propanol, (CH3)2CHOH, on a Si(111)-7x7 surface was studied by scanning tunneling microscopy. (CH3)2CHOH adsorbs equally on the faulted and unfaulted half unit cells by forming Si-OCH(CH3)2 and Si-H on an adatom and rest atom pair. Si-OCH(CH3)2 is consecutively increased in each half unit cell, and the adsorption is saturated when every half unit cell has three Si-OCH(CH3)2, which corresponds to 0.5 of the adatom coverage. The sticking probability for the dissociation of (CH3)2CHOH is independent of the adatom coverage from 0 to 0.4, but it depends on coverage at higher than 0.4. By counting the darkened adatoms, Si-OCH(CH3)2 on the center adatom (m) and that on the corner adatom (n), it was found the m/n ratio is ca. 4 for the first dissociation of (CH3)2CHOH in virgin half unit cell, but it becomes ca. 1.9 and 1.8 when two and three Si-OCH(CH3)2 are contained in a half unit cell. This result reveals that the dissociation probability of (CH3)2CHOH at the adatom-rest atom pair site is influenced by the nearest Si-OCH(CH3)2 in the half unit cell.     

Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

The first copper‐catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.     

Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts

A Ru‐catalyzed direct C? H activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future C? H activation development that would allow the remote functionalization of aromatic systems.     

De Novo Design and Synthesis of a γ‐Turn Peptidomimetic Scaffold and Its Application as JNK3 Allosteric Ligand

As a way to develop a neuroprotective agent for the JNK3‐JIP1‐binding site, peptidomimetics of JIP‐1 as JNK3 allosteric regulators have been examined. The study consisted of in silico scaffold hopping, molecular docking, solution and solid‐phase peptide syntheses, and K_d measurements using surface plasmon resonance. As a peptidomimetic of JIP1, heptamer mimetic 16 (K_d=2.72 μm ) displayed a higher affinity than decamer JIP1 (K_d=23.6 μm ). The high affinity of 16 implies that the characteristic γ‐turn mimetic structure, “”Φ‐X‐Φ“ hydrophobic motif in 16 , increased its affinity toward the JIP‐site of JNK3.