Intermolecular-medium and intramolecular-weak hydrogen bonding chains in the crystals of chiral trifluoromethylated amino alcohols

A structural feature of hydrogen bonding chains found in the crystals of trifluoromethylated amino alcohols is reported. Hydrogen bondings of 3-(N,N-dialkylamino)-1,1,1-trifluoro-2-propanols construct chiral spiral hydrogen bonding chains. Lone pairs on the nitrogen atoms of the amino alcohols participate in two hydrogen bondings. Detailed structural analysis of the hydrogen bonds of the 3-(N,N-dimethylamino)-1,1,1-trifluoro-2-propanol suggested that the chain built up with alternating intermolecular-medium and intramolecular-weak hydrogen bonds. The medium intermolecular hydrogen bond, which transfers a proton from the hydroxy group to the amino nitrogen, would make a tentative zwitterionic form of the molecule. Then, electrostatic attraction between the charges in the zwitterion centers induced a weak intramolecular hydrogen bond.     

Development of a stable isotope dilution UPLC‐MS/MS method for quantification of dexmedetomidine in a small amount of human plasma

Dexmedetomidine (Dex) is a selective central α2‐agonist with anesthetic properties and has been used in clinical practice for sedation in the intensive care unit (ICU) after operations. In this study, an analytical assay for the determination of Dex in a small amount of plasma was developed for the application to pediatric ICU trials. The quantification of Dex was constructed using the original stable isotope Dex‐d₃ for electrospray ionization‐tandem mass spectrometry (ESI‐MS/MS) in the selected reaction monitoring mode. A rapid ultra‐performance liquid chromatography technique was adopted using ESI‐MS/MS with a runtime of 3 min. Efficacious concentration levels (50 pg/mL to 5 ng/mL) could be evaluated using a very small amount of plasma (10 μL) from patients. The lower limit of the quantification was 5 pg/mL in the plasma (100 µL). For sample preparation, a solid‐phase extraction was used along with the OASIS‐HLB cartridge type. Recovery values ranged from 98.8 to 100.3% for the intra‐ [relative standard deviation (RSD), 0.9–1.3%] and inter‐ (RSD, 0.9–1.5%) day assays. A stable test had recovery values that ranged from 97.8 to 99.7% with an RSD of 1.0–1.9% for the process/wet extract, bench‐top, freeze–thaw and long‐term tests. This method was used to measure the Dex levels in plasma from pediatric ICU patients. In the clinical ICU trial, the small amount of blood (approximate plasma volume, 200 μL) remaining from blood gas analysis was reused and targeted for the clinical analysis of Dex in plasma. Copyright © 2013 John Wiley & Sons, Ltd.     

Uric acid quantification in fingernail of gout patients and healthy volunteers using HPLC‐UV

The presence of elevated uric acid (UA) levels is a sign of gout, that is, hyperuricemia. In this study the monitoring of the UA levels in less‐invasive biological samples, such as the human fingernail, is suggested for the diagnosis and therapy of gout. Twenty‐six healthy volunteers (HV) and 22 gout patients (GP) were studied. The UA was extracted from human fingernail samples, then separated on an Inertsil ODS‐3 column (250 × 4.6 mm i.d., 4.0 μm, GL Sciences) by isocratic elution using methanol–74 mm phosphate buffer (pH 2.2) 2:98 (v/v). A UV detector was used to monitor the samples at 284 nm. Using the developed method, different UA concentrations were found in the GP and HV. When comparing the concentrations from GP with those from HV, a statistically significant correlation was observed between the UA (p < 0.01). In this study, the UA was confirmed as a potential biomarker for the diagnosis and therapy of gout. We have developed a novel sensitive, and simple method for the determination of UA in the fingernails of GP and HV. The human fingernail may serve as a noninvasive biosample for the diagnosis of gout. Copyright © 2016 John Wiley & Sons, Ltd.     

Cu-deposits on Mg metal surfaces promote electron transfer reactions

The enhancement of the electron transfer processes in the Grignard reagent formation-type ring silylation and the defluorination–silylation of perfluoroalkyl benzenes by Cu(0)-deposited Mg metal were confirmed. Microscopic analysis and substituent effects implied a different reduction process in the presence of Cu-deposited Mg metal than in the presence of bare Mg metal.     

Organometallic Molecular Wires with Thioacetylene Backbones,trans-{RS-(C≡C)n}2Ru(phosphine)4: High Conductance through Non-Aromatic Bridging Linkers

In this work, the design, synthesis, and single-molecule conductance of ethynyl- and butadiynyl-ruthenium molecular wires with thioether anchor groups [RS=n-C₆H₁₃S, p-tert-Bu−C₆H₄S), trans-{RS−(C≡C)_n}₂Ru(dppe)₂ (n=1 ( 1^R ), 2 ( 2^R ); dppe: 1,2-bis(diphenylphosphino)ethane) and trans-(n-C₆H₁₃S−C≡C)₂Ru{P(OMe)₃}₄ 3^hex ] are reported. Scanning tunneling microscope break-junction study has revealed conductance of the organometallic molecular wires with the thioacetylene backbones higher than that of the related organometallic wires having arylethynylruthenium linkages with the sulfur anchor groups, trans-{p-MeS−C₆H₄-(C≡C)_n}₂Ru(phosphine)₄ 4 ⁿ (n=1, 2) and trans-(Th−C≡C)₂Ru(phosphine)₄ 5 (Th=3-thienyl). It should be noted that the molecular junctions constructed from the butadiynyl wire 2^R , trans-{ Au −RS−(C≡C)₂}₂Ru(dppe)₂ ( Au : gold metal electrode), show conductance comparable to that of the covalently linked polyynyl wire with the similar molecular length, trans-{ Au −(C≡C)₃}₂Ru(dppe)₂ 6³ . The DFT non-equilibrium Green's function (NEGF) study supports the highly conducting nature of the thioacetylene molecular wires through HOMO orbitals.     

A novel derivatization reagent possessing a bromoquinolinium structure for biological carboxylic acids in HPLC‐ESI‐MS/MS

A novel bromoquinolinium reagent, i.e. 1‐(3‐aminopropyl)‐3‐bromoquinolinium bromide (APBQ), was synthesized for the analysis of carboxylic acids. A simple and practical precolumn derivatization procedure using the APBQ in RP chromatography and MS (HPLC‐MS) has been developed using bile acids and free fatty acids, as the representative carboxylic acids in biological samples. The APBQ efficiently reacted with carboxylic acids at 60°C for 60 min in the presence of N,N‐dicyclohexylcarbodiimide and pyridine as the activation reagents. Because the APBQ possesses a bromine atom in the structure, the identification of a series of carboxylic acids was easily achieved due to the characteristic bromine isotope pattern in the mass spectra. The APBQ also has a quaternary amine structure, thus the positively charged derivatives are predominate for the highly sensitive detection of carboxylic acids. The APBQ was successfully applied to the selective determination of biological carboxylic acids in human plasma. The bile acids (chenodeoxycholic acid and deoxycholic acid) and several saturated (stearic acid and palmitic acid) and unsaturated free fatty acids (oleic acid and linoleic acid) were reasonably determined by HPLC‐MS under the proposed procedure. Based on the results of analyses of human plasma and saliva, the proposed procedure using APBQ seems to be applicable for the qualitative and quantitative analyses of a series of carboxylic acids in biological samples.     

Two‐dimensional replica‐exchange method for predicting protein–ligand binding structures

We have developed a two‐dimensional replica‐exchange method for the prediction of protein–ligand binding structures. The first dimension is the umbrella sampling along the reaction coordinate, which is the distance between a protein binding pocket and a ligand. The second dimension is the solute tempering, in which the interaction between a ligand and a protein and water is weakened. The second dimension is introduced to make a ligand follow the umbrella potential more easily and enhance the binding events, which should improve the sampling efficiency. As test cases, we applied our method to two protein‐ligand complex systems (MDM2 and HSP 90‐alpha). Starting from the configuration in which the protein and the ligand are far away from each other in each system, our method predicted the ligand binding structures in excellent agreement with the experimental data from Protein Data Bank much faster with the improved sampling efficiency than the replica‐exchange umbrella sampling method that we have previously developed. © 2013 Wiley Periodicals, Inc.     

2-Chloroanthraquinone-catalyzed aerobic photo-oxidative synthesis of diacylamines from benzylamides

In this Letter, we report the aerobic photo-oxidative synthesis of diacylamines from benzylamides in the presence of molecular oxygen and catalytic amounts of 2-chloroanthraquinones under visible light irradiation from a fluorescent lamp.     

Evaluation of a series of prolylamidepyridines as the chiral derivatization reagents for enantioseparation of carboxylic acids by LC–ESI–MS/MS and the application to human saliva

Mass spectrometry has become a popular analytical tool because of its high sensitivity and specificity. The use of a chiral derivatization reagent for the mass spectrometry (MS) detection seems to be efficient for the enantiomeric separation of racemates. However, the number of chiral reagents for the liquid chromatography (LC)–MS/MS analysis is very limited. According to these observations, we are currently in the process of developing novel labeling reagents for chiral molecules in MS/MS analysis. The derivatization reagent that is effective for enhancing not only the electrospray ionization–MS/MS sensitivity but also the reversed-phase LC resolution of carboxylic acid enantiomers should have a highly proton-affinitive moiety and an asymmetric structure near the reactive functional group. Furthermore, the resulting derivative has to provide a characteristic product ion suitable for the selected reaction monitoring. Based upon these considerations, a series of prolylamidepyridines ((S)-N-pyrrolidine-2-carboxylic acid N-(pyridine-2-yl)amide (PCP2), (S)-N-pyrrolidine-2-carboxylic acid N-(pyridine-3-yl)amide, and (S)-N-pyrrolidine-2-carboxylic acid N-(pyridine-4-yl)amide) was synthesized as ideal labeling reagents for the enantioseparation of chiral carboxylic acids and evaluated in terms of separation efficiency and detection sensitivity by ultra-performance LC (UPLC)–MS/MS. Among the synthesized reagents, PCP2 was the most efficient chiral derivatization reagent for the enantioseparation of carboxylic acid. The Rs values and the detection limits of the derivatives of non-steroidal anti-inflammatory drugs, which were selected as the representative carboxylic acids, were in the range of 2.52–6.07 and 49–260 amol, respectively. The sensitive detection of biological carboxylic acids (detection limits, 32–520 amol) was also carried out by the proposed method using PCP2 and UPLC–MS/MS. The PCP2 was applied to the determination of carboxylic acids in human saliva. Several biological carboxylic acids, such as lactic acid (LA), 3-hydroxybutylic acid, maric acid, succinic acid, α-ketoglutalic acid, and citric acid, were clearly identified in the saliva of healthy persons and diabetic patients. Furthermore, the ratio of d-LA in diabetic patients was higher than that in normal subjects. Judging from these results, PCP2 seems to be a useful chiral derivatization reagent for the determination not only of chiral, but also achiral, carboxylic acids in real samples.