Determination of dimethylated nucleosides in serum from colorectal cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

RNA modifications play a crucial regulatory role in a variety of biological processes and are closely related to numerous diseases, including cancer. The diversity of metabolites in serum makes it a favored biofluid for biomarkers discovery. In this work, a robust and accurate hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach was established for simultaneous determination of dimethylated nucleosides in human serum.

Identification of animal species of origin in meat based on glycopeptide analysis by UPLC-QTOF-MS.

Adulteration of meat and meat products causes a concerning threat for consumers. It is necessary to develop novel robust and sensitive methods which can authenticate the origin of meat species to compensate for the drawbacks of existing methods. In the present study, the sarcoplasmic proteins of six meat species, namely, pork, beef, mutton, chicken, duck and turkey, were analyzed by one-dimensional gel electrophoresis.

Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8.

Study on the anti-gout activity of the lotus seed pod by UPLC-QTOF-MS and virtual molecular docking.

The lotus seed pod is one of the main organs of the lotus plant and is commonly used in traditional medicine. It is believed to have dehumidifying and anti-rheumatic effects. This study, utilized the non-targeted approach of identification via UPLC-QTOF-MS/MS to identify the main chemical components in the lotus seed pod extracts and found a total of 118 compounds.

Determination of adenosine and its modifications in urine and plasma from breast cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

RNA modifications have been revealed to be essential in many biological activities, and their disorders are associated with various human diseases, including cancers. 2'-O-methyladenosine (A), N-methyladenosine (mA), N-methyladenosine (mA), N,2'-O-dimethyladenosine (mA) and N,N-dimethyladenosine (mA) are important adenosine (A) modifications. The noninvasive collection of urine samples and the diverse contents of metabolites in plasma make them favored biofluids for biomarkers discovery.

An Improved GC-MS Method for Malondialdehyde (MDA) Detection: Avoiding the Effects of Nitrite in Foods.

Malondialdehyde (MDA) is one of the representative end products under lipid peroxidation, indicating the degree of lipid oxidation in foods. However, compounds in pickled products, especially the nitrite in salted lean pork can react with MDA under the acidic condition, leads to the loss of MDA and an underestimation on lipid oxidation through the conventional assay. In this study, the quantification for MDA in the sample containing sodium nitrite were found lacking accuracy by the thiobarbituric acid (TBA) assay and chromatography assay based on alkaline hydrolysis as the reaction between them were difficult to be completely inhibited.

Green Extraction-Assisted Pseudo-Targeted Profile of Alkaloids in Lotus Seed Epicarp Based on UPLC-QTOF MS with IDA.

Lotus seed epicarp, a byproduct of lotus, is commonly discarded directly or burned in the cropland, resulting in waste of resources and environmental pollution. In this work, a green ultrasonic-assisted extraction method with ethyl lactate as the extraction solvent was established to extract alkaloids from lotus seed epicarp. The extraction conditions were optimized by response surface methodology.

HILIC-MS/MS for the Determination of Methylated Adenine Nucleosides in Human Urine.

-methyl-2'-deoxyadenosine (mdA) is a newly discovered DNA epigenetic mark in mammals. -methyladenosine (mA), 2'--methyladenosine (A), ,2'--dimethyladenosine (mA), and ,-dimethyladenosine (mA) are common RNA modifications. Previous studies illustrated the associations between the aberrations of these methylated adenosines in nucleic acids and cancer.

Investigating the exceptional adducts of alkoxides with Ru(II)-arene cations in alkyl alcohol solution using electrospray ionization mass spectrometry.

Rationale: Exploring the formation mechanism of the exceptional adducts of alkoxides with Ru(II)-arene cations in alkyl alcohol solution using electrospray ionization mass spectrometry (ESI-MS) is crucial for further understanding the physicochemical properties of Ru(II)-arene complexes in solution.

Methods: All mass spectra were collected with an AB SCIEX TripleTOF 5600 mass spectrometer in positive mode. Theoretical calculations were carried out using the density functional theory method at the B3LYP level with a hybrid basis set consisting of 6-31G(d,p) and LanL2DZ in the Gaussian 03 program.

Electrochemically Enabled Sulfonylation of Alkynes with Sodium Sulfinates.

An electrochemical sulfonylation of alkynes with sodium sulfinates was achieved for the first time at room temperature. Employing this electrolysis strategy, the reaction occurs efficiently under transition-metal-free, external oxidant-free, and base-free conditions and furnishes diverse alkynyl sulfones in satisfactory yield with broad functional group tolerance.

Synthesis of Spiroisoxazolines via TEMPO/NaNO-Catalyzed Aerobic Oxidative Dearomatization.

A catalytic, aerobic oxidative dearomatization protocol has been developed for the preparation of spiroisoxazline scaffolds from oximes using TEMPO and NaNO as the catalyst and O as the sole oxidant. This dearomatization methodology features its mild reaction conditions, good functional group tolerance, and an unprecedented broad substrate scope, encompassing phenols, aryl ethers, thiophenols, aryl sulfides, etc.

A modified quick, easy, cheap, effective, rugged, and safe method with hydrophobic natural deep eutectic solvent as extractant and analyte protectant for analyzing pyrethroid residues in tomatoes.

In this work, a novel quick, easy, cheap, effective, rugged, and safe technique with hydrophobic natural deep eutectic solvent as both extractant and analyte protectant was developed and combined with gas chromatography-tandem mass spectrometry to analyze pyrethroid residues in tomatoes. Eight hydrophobic natural deep eutectic solvents were first evaluated as analyte protectants and those with decanoic acid or lactic acid as hydrogen bond donor were demonstrated to be effective in compensating for the matrix effects of pyrethroids in the gas chromatography system. Hence, they were added to solvent standards for correcting the quantitation errors instead of matrix-matched calibration standards.

Dispersive liquid-liquid extraction based on magnetic Pickering emulsion followed by gas chromatography-tandem mass spectrometry for the simultaneous determination of aldehydes in environmental water samples.

A dispersive liquid-liquid extraction based on Pickering emulsion stabilized with ferroferric oxide grafted nitrogen-doped graphitized carbon black has been developed to simultaneously determine seven aldehydes in environmental water samples, in combination with pentafluorobenzyl hydroxylamine precolumn derivatization gas chromatography-tandem mass spectrometry. The nitrogen-doped graphitized carbon was prepared from dicyandiamide waste residue with a simple acid wash process. The effects of magnetic emulsifier amount, extraction time, solution pH, and oil/water volume ratio on the formation of magnetically responsive Pickering emulsion and the extraction efficiency of the proposed dispersive liquid-liquid extraction were also investigated.

Electrochemical Oxidative Oxydihalogenation of Alkynes for the Synthesis of α,α-Dihaloketones.

An electrochemical oxydihalogenation of alkynes has been developed for the first time. Using this sustainable protocol, a variety of α,α-dihaloketones can be prepared with readily available CHCl, CHCl, ClCHCHCl, and CHBr as the halogen source under electrochemical conditions at room temperature.

In-Water Synthesis of 5-Thiolated 1,2,3-Triazoles from β-Thioenaminones by Diazo Transfer Reaction.

The synthesis of 1,2,3-triazoles with a sulfur-based side chain has been accessed with the metal-free annulation reactions of readily available β-thiolated enaminones and tosyl hydrazine. By these reactions with water as the only medium, a broad array of 5-thiolated 1,2,3-triazoles have been synthesized with generally good to excellent yields. Except using TMEDA (,,','-tetramethylethylenediamine) as the only base promoter, not any other catalyst or additive is required, thus providing an efficient and environmentally benign method for useful 1,2,3-triazole synthesis.

Synthesis of polysubstituted cyclic 1,2-diketones enabled by iterative sulfoxide-mediated arylation.

A metal-free α-C-H functionalization of cyclic 1,2-diketones with aryl sulfoxides has been developed. This regioselective arylation involves nucleophilic substitution at the activated sulfoxide with a diosphenol, followed by [3,3]-sigmatropic rearrangement. This protocol can also be applied to the synthesis of polysubstituted cyclic 1,2-diketones with predictable structures by iterative arylations.

Metal-Free Cyclopropanol Ring-Opening C(sp)-C(sp) Cross-Couplings with Aryl Sulfoxides.

A metal-free method for formal β-arylation/heteroarylation of ketones through efficient cyclopropanol ring-opening cross-couplings with aryl sulfoxides at room temperature has been developed. This protocol shows a broad substrate scope and promising scalability. In addition, the utility of the β-arylated ketones is further demonstrated through a variety of postcoupling transformations and synthetic applications.

A novel malic acid-enhanced method for the analysis of 5-methyl-2'-deoxycytidine, 5-hydroxymethyl-2'-deoxycytidine, 5-methylcytidine and 5-hydroxymethylcytidine in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

5-Methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5-methylcytidine (5-mrC) and 5-hydroxymethylcytidine (5-hmrC) are epigenetic marks of DNA and RNA, and aberrant levels of these modified nucleosides were found to be associated with various cancers. Urine is a preferred source of biological fluid for biomarker discovery because the sample collection process is not invasive to patients. Herein, we developed a novel malic acid-enhanced hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for sensitive and simultaneous quantification of the modified cytosine nucleosides in human urine.

Comparing the fragmentation reactions of protonated cyclic indolyl α-amino esters in quadrupole/orbitrap and quadrupole time-of-flight mass spectrometers.

Rationale: The comparative study of higher-energy collisional dissociation (HCD) and collision-induced dissociation (CID) mechanisms for protonated cyclic indolyl α-amino esters in quadrupole/orbitrap (Q/Orbitrap) and quadrupole time-of-flight (QTOF) mass spectrometers, respectively, is helpful to study the structures and properties of biologically active indole derivatives using tandem mass spectrometry (MS/MS) technology.

Methods: HCD and CID experiments were carried out using electrospray ionization Q/Orbitrap MS and QTOFMS in positive ion mode, respectively. Only the labile hydrogens were exchanged with deuterium in hydrogen/deuterium exchange (HDX) experiments and only the aromatic indole C-H hydrogens were substituted with deuterium in regiospecific hydrogen-deuterium labeling experiments.

Quantification of glycocholic acid in human serum by stable isotope dilution ultra performance liquid chromatography electrospray ionization tandem mass spectrometry.

A rapid, accurate and sensitive stable isotope dilution ultra performance liquidchromatography electrospray ionization tandem mass spectrometry (ID-UPLC-ESI-MS/MS) method for the determination of glycocholic acid (GCA) in human serum was developed and validated. Serum samples were spiked with D-glycocholic acid and then pretreated with protein precipitation. The analysis was performed on a Waters BEH C18 column (100 mm×2.

Regioselective three-component synthesis of 2,3-disubstituted quinolines via the enaminone modified Povarov reaction.

The regioselective construction of functionalized quinolines by the three-component reactions of enaminones, aldehydes and anilines is accomplished. Unlike conventional Povarov reactions employing terminal alkynes or alkenes as C3-C4 fragment sources which provide 2,4-disubstituted quinolines, the present method allows fast and regioselective formation of 2,3-disubstituted quinolines as a modified new version of the Povarov reaction.

Potential application of the oxidative nucleic acid damage biomarkers in detection of diseases.

Reactive oxygen species (ROS) are generated after exposure to harmful environmental factors and during normal cellular metabolic processes. The balance of the generating and scavenging of ROS plays a significant role in living cells. The accumulation of ROS will lead to oxidative damage to biomolecules including nucleic acid.

Discriminating patients with early-stage breast cancer from benign lesions by detection of oxidative DNA damage biomarker in urine.

Breast cancer is one of the most commonly diagnosed and death-related cancers in women worldwide. Mammography is routinely used for screening and invasive examinations such as painful tissue biopsies were recommended for patients with abnormal screening outcomes. However, a considerable proportion of these cases turn out to be benign lesions.

Mechanism investigation of HS radical and CS losses from positively charged biradicals of diphenyl sulfides by APCI mass spectrometry.

Rationale: Aryl thioethers are potentially useful precursors for constructing various biologically active sulfur-containing heterocycles. The detailed relationship between the losses of HS radical and CS with the spin multiplicity of positively charged diphenyl sulfide biradicals derived from 3-iodophenyl phenyl sulfides has not been obtained by tandem mass spectrometry combined with theoretical calculations.

Methods: Collision-induced dissociation mass spectrometry experiments were carried out using an ion trap mass spectrometer with APCI in positive mode.

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp(3))-H arylation.

The synthesis of β-arylated alkylamides via alkyl C-H bond arylation has been realized by means of direct one-pot reactions of acyl chlorides, aryl iodides and 8-aminoquinoline. Depending on the structure of the starting materials, both single and double β-arylated alkylamides could be accessed.