Shift Reagent Research Articles

The adduction behavior of water reactant ions with mobility shift reagents in ion mobility spectrometry is determined by the number of locations for adduction, interaction energies, proton affinities, and steric hindrance of these species

The introduction of mobility shift reagents (SRs) into the buffer gas of mobility spectrometers yields SR-ion clusters that decrease ion mobilities and allow the separation of overlapping ions. With a large amount of papers on the introduction of SRs in ion mobility spectrometry (IMS) few investigations explain the behavior of the adducts of reactant ions with SRs and it is not clear what type of peaks to expect which obscures the interpretation of spectra. Electrospray-ionization IMS was coupled to quadrupole mass spectrometry, and 2-butanol (B), ethyl lactate (L), and methanol were introduced as SRs into the buffer gas. The hybrid functional X3LYP/6–311++(d,p) with Gaussian 09 was used for theoretical calculations of SR-ion interaction energies. Adducts of the reactant ions with B and L presented different behaviors; even at low flow rates, L consumed all sodium, reactant ions, and water by adduction, because a) in the experimental conditions, SRs were more concentrated in the buffer gas than reactant ions, b) L’s high proton affinity and c) L’s three electron-donor oxygens, increases adduction. Therefore, chemical equilibria in the buffer gas were only between L and LnH+, LmH3O+, or LxNa+ adducts and, consequently, these sets of adducts had different mobilities. The lower mobility of LmH3O+ compared to LnH+ was explained on the base of the lower steric hindrance in LH3O+ for attachment of L molecules. The behavior of reactant ions with B was different: BnH3O+ and BnH+ overlapped because the relatively low proton affinity and the single and weaker interaction site in B allowed protons and water to be exchanged between species. Finally, L4H+, L4H3O+, B4H+ and B5H+ ions, not reported before, were seen for large SR concentrations. This study explains two different behaviors of the adducts of SRs with reactant ions using interaction energies, proton affinities, steric hindrance, and the number of locations for adduction.

Shift reagents in ion mobility spectrometry: the effect of the number of interaction sites, size and interaction energies on the mobilities of valinol and ethanolamine.

Overlapping peaks interfere in ion mobility spectrometry (IMS), but they are separated introducing mobility shift reagents (SR) in the buffer gas forming adducts with different collision cross-sections (size). IMS separations using SR depend on the ion mobility shifts which are governed by adduct's size and interaction energies (stabilities). Mobility shifts of valinol and ethanolamine ions were measured by electrospray-ionization ion mobility-mass spectrometry (MS). Methyl-chloro propionate (M) was used as SR; 2-butanol (B) and nitrobenzene (N) were used for comparison. Density functional theory was used for calculations. B produced the smallest mobility shifts because of its small size. M and N have two strong interaction sites (oxygen atoms) and similar molecular mass, and they should produce similar shifts. For both ethanolamine and valinol ions, stabilities were larger for N adducts than those of M. With ethanolamine, M produced a 68% shift, large compared to that using N, 61%, because M has a third weak interaction site on the chlorine atom and, therefore, M has more interaction possibilities than N. This third site overrode the oxygen atoms' interaction energy that favored the adduction of ethanolamine with N over that with M. On the contrary, with valinol mobility shifts were larger with N than with M (21 vs 18%) because interaction energy favored even more adduction of valinol with N than with M; that is, the interaction energy difference between adducts of valinol with M and N was larger than that between those adducts with ethanolamine, and the third M interaction could not override this larger difference. Mobility shifts were explained based on the number of SR's interaction sites, size of ions and SR, and SR-ion interaction energies. This is the first time that the number of interaction sites is used to explain mobility shifts in SR-assisted IMS. Copyright © 2016 John Wiley & Sons, Ltd.

Lithium Enolates Derived from Pyroglutaminol: Aggregation, Solvation, and Atropisomerism.

Lithium enolates derived from protected pyroglutaminols were characterized by using (6)Li, (13)C, and (19)F NMR spectroscopies in conjunction with the method of continuous variations. Mixtures of tetrasolvated dimers and tetrasolvated tetramers in different proportions depend on the steric demands of the hemiaminal protecting group, tetrahydrofuran concentration, and the presence or absence of an α-fluoro moiety. The high steric demands of the substituted bicyclo[3.3.0] ring system promote dimers to an unusual extent and allow solvents and atropisomers in cubic tetramers to be observed in the slow-exchange limit. Pyridine used as a (6)Li chemical shift reagent proved useful in assigning solvation numbers.

Monitoring changes of paramagnetically-shifted 31P signals in phospholipid vesicles

Phospholipid vesicles are commonly used as biomimetics in the investigation of the interaction of various species with cell membranes. In this letter we present a 31P NMR investigation of a simple vesicle system using a paramagnetic shift reagent to probe the inner and outer layers of the lipid bilayer. Time-dependent changes in the 31P NMR signal are observed, which differ whether the paramagnetic species is inside or outside the vesicle, and on the choice of buffer solution used. An interpretation of these results is given in terms of the interaction of the paramagnetic shift reagent with the lipids.

LipoCEST and cellCEST imaging agents: opportunities and challenges.

From the early days of CEST agents' disclosure, it was evident that their potential for in vivo applications was strongly hampered by the intrinsic low sensitivity. Therefore, much work has been devoted to seek out suitable routes to achieve strong CEST contrast enhancement. The use of nanosized systems turned out to be a strategic choice, because a very large amount of CEST agents can be delivered at the site of interest. However, the breakthrough innovation in term of increase of sensitivity was found by designing the lipoCEST agents. The naturally inspired, liposomes vesicles, when loaded with paramagnetic lanthanide-based shift reagents, can be transformed into CEST probes. The large number of water molecules entrapped inside the inner cavity of the nanovesicles represents an enormous pool of exchanging protons for the generation of CEST contrast, whereas the presence of the shift reagent increases the separation in chemical shift of their nuclear magnetic resonance signal from that of the bulk water, thus allowing for a proper exchange regime for the activation of CEST contrast. From lipoCEST, it has been rather straightforward to evolve to cellCEST in order to exploit the cytoplasmatic water molecules as source of the CEST effect, once cells have been loaded with the proper shift reagent. The red blood cells were found to be particularly suitable for the development of the cellCEST concept. Finally, an understanding of the main determinants of the CEST effects in nanosized and cellular-sized agents has allowed the design of innovative lipoCEST/RBC aggregates for potential theranostic applications. WIREs Nanomed Nanobiotechnol 2016, 8:602-618. doi: 10.1002/wnan.1385 For further resources related to this article, please visit the WIREs website.

DOSY NMR: A Versatile Analytical Chromatographic Tool for Lignocellulosic Biomass Conversion

The diffusion ordered NMR spectroscopy (DOSY) protocol for the analysis of reaction mixture of lignocellulosic biomass conversion has been developed and investigated systematically. Model reaction mixtures from cellulose, hemicellulose and lignin conversion, real reaction mixtures of sucrose and glucose dehydration, were facilely separated and assigned in the diffusion dimension without any prior separation or isolation. The shift reagent, EuFOD, was successfully utilized to increase the difference in diffusion and thereby resolution in lignin degradation model. DOSY NMR offers an easy and robust method for the structure identification and reaction mixture separation in biomass conversion.

The Bull-James assembly as a chiral auxiliary and shift reagent in kinetic resolution of alkyne amines by the CuAAC reaction.

The Bull-James boronic acid assembly is used simultaneously as a chiral auxiliary for kinetic resolution and as a chiral shift reagent for in situ enantiomeric excess (ee) determination by 1H NMR spectroscopy. Chiral terminal alkyne-containing amines, and their corresponding chiral triazoles formed via CuAAC, were probed in situ. Selectivity factors of up to s = 4 were imparted and measured, accurate to within ±3% when compared to chiral GC.

Immunomodulatory pinguisane-type sesquiterpenes from the liverwort Porella cordaeana (Porellaceae): the “new old” furanopinguisanol and its oxidation product exert mutually different effects on rat splenocytes

α-Furanopinguisanol and furanopinguisanone, two new pinguisane-type sesquiterpenes from the liverwortPorella cordaeana, exert mutually different effects on rat splenocytes.

Isolation and Identification of a Flavone Apigenin from Marine Red Alga Acanthophora spicifera with Antinociceptive and Anti-Inflammatory Activities.

Physicochemical investigation of the red alga Acanthophora spicifera (Vahl) Borgesen, collected from Al-Shoaiba coast, Red Sea, Saudi Arabia, led to the isolation of a flavone from the algal tissue with acetone. Preparative chromatography on silica gel thin-layer chromatography was used for the separation of the flavone and eluted with the methanol:chloroform:ethyl acetate (1:7:2) solvent system. The physicochemical analyses infrared, mass spectra, and ultraviolet spectra in addition to shift reagents (NaOMe, NaOAc, NaOAc + H3BO3, AlCl3, and AlCl3 + HCl) were used for the identification and elucidation of the structure of the flavone compound (4,5,7-trihydroxy flavonoids). The flavone compound was identified as apigenin bycomparing its physicochemical data with those in the literature. Analgesic and anti-inflammatory activities of apigenin were evaluated. Apigenin showed promising analgesic and anti-inflammatory activities in the hot plate test and writhing test in mice as well as tail-immersion tests and carrageenan-induced paw edema and cotton pellet-induced granuloma formation in rats. It is concluded that apigenin possesses potent analgesic, anti-inflammatory, and antiproliferative activities, which might be due to the inhibition of PGE2 as well as proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α.

Trifluoromethyl benzyl alcohol as a “shift reagent” in ion mobility spectrometry: The effect of intramolecular bridges, ion size and shift reagent-ion binding energy in ion mobility

α-Trifluoromethyl benzyl alcohol (F) was introduced as a “shift reagent” in the buffer gas of an electrospray ionization ion mobility spectrometer coupled to a quadrupole mass spectrometer to explain the mobility shifts of selected compounds; ion mobilities depended on ion sizes and F-ion adducts binding energies calculated using Gaussian 09 at the X3LYP/6-311++G(d,p) level. The mobility shifts with the introduction of F in the buffer gas were: −13% (ethanolamine), −10.6% (serine), −8.6% (threonine), −7.3% (phenylalanine), −7.0% (tyrosine), −6.2 (tributylamine), −5.1% (valinol), −4.7% (methionine), −3.9% (tryptophan), −3.1% (tribenzylamine), −1.3% (2,6-di-tert-butyl pyridine, DTBP), −1.2% (2,4-lutidine, 2,4-dimethyl pyridine), and −0.1% (atenolol). These mobility shifts showed a decreasing trend with the increase in molecular weight from ethanolamine to tribenzylamine excluding some ions due to steric hindrance (2,4-lutidine, DTBP and tetraalkylammonium ions), formation of intramolecular bridges (atenolol and methionine) or low binding energy with F (valinol). Ethanolamine (61.1g/mol) showed the largest mobility shift (−13%) due to its low molecular weight and tribenzylamine showed the smallest one due to its large size. We found a similar trend in mobility shifts when methyl chloro propionate, trifluoromethyl benzyl alcohol, ethyl lactate, nitrobenzene or 2-butanol were used as SRs. We also found that penicillamine adducts with F were not seen in the mass or mobility spectra probably because of the formation of an intramolecular bridge in this compound; F produced the average lowest mobility shifts of all SRs tried before, even of smaller size (methyl chloro propionate, phenylethanol, ethyl lactate, nitrobenzene, and 2-butanol) because of the inductive effects exerted by the three fluorine atoms that decreased F proton affinity and hindered its adduction to analyte ions. In summary, intramolecular bridges, size, inductive effects, steric hindrance and adduct binding energy were used to explain mobility shifts when trifluoromethyl benzyl alcohol was used as a “shift reagent” in ion mobility spectrometry.

Anatomical characteristics and tissue localization of various flavonoid subclasses in Cotinus coggygria stem and leaf cross-sections

Leaves, twigs and wood of Cotinus coggygria (Anacardiaceae) are employed in European and Chinese traditional medicine to treat skin and mucosal injuries, fever, diarrhea, emesis and to enhance appetite. While being a popular medicinal plant, ancient tinctorial species and common ornamental shrub, its anatomical characteristics and tissue localization of major groups of active compounds have not been studied yet, to the best of our knowledge. Freehand cross sections of the stem at different developmental stages, leaf lamina and petiole were performed. Tissue types were studied using conventional dyes (toluidine blue; congo red and malachite green). Folin-Ciocalteu reagent, shift reagents (ammonia) and Naturstoffreagenz A were used to complement light microscopy and autofluorescence observations of flavonoid localization. Microscopes of type Optika XDS-3FL inverted fluorescence, and Olympus BH-2 for observation in visible light were employed. C. coggygria stem has a typical secondary structure. The bark contains resin ducts placed in the phloem; in younger twigs they are limited by outer sclerenchyma arches. Vascular cambium generates distinct annual rings, with a porous structure. The vessel frequency is of 100 – 200 mm2, and their perforations are simple. Medullar rays are narrow (1 – 2 cells). Chalcone and aurone derivatives are present in inner wood rings aged at least 2 years, in earlywood parts. Leaves display epidermis with anomocytic stomata on the lower surface. A hypodermis is present on the adaxial side. The midrib contains four main vascular bundles and cambium. The phloem encloses resin secretory cavities. The center of the midrib is occupied by parenchyma. Palisade parenchyma is two cells deep, and spongy mesophyll is situated towards the abaxial side. Reducing flavonoids are present in leaf mesophyll.

Reinvestigation of a Catalytic, Enantioselective Alkene Dibromination and Chlorohydroxylation.

Attempts to reproduce eight, putative, enantioselective dibromination and chlorohydroxylation reactions from oft-cited literature studies are described. The reactions were performed with full fidelity to the original report wherever possible. Analysis of the enantiomeric composition was performed by chiral stationary phase HPLC or SFC (CSP-HPLC or CSP-SFC), as opposed to the original report, which used chiral shift reagent NMR spectroscopy. After careful study, the reported levels of enantioselectivity were found to be incorrect. Possible explanations for the false positive results are discussed.

ISOLASI DAN IDENTIFIKASI SENYAWA FLAVONOID DARI EKSTRAK ETANOL BUAH BELIMBING WULUH (Averrhoa bilimbi L.) DENGAN METODE SPEKTROFOTOMETRI UV-VIS

Star fruits (Averrhoa bilimbi L.) from family of oxalidaceae is a plant which has potential as an antibacterial Staphylococcus aureus and Escherichia coli. Flavonoid are the active compounds from the extract of star fruit which has potential as an antibacterial. Star fruit were extracting by ethanol 96 % using maceration. Extract were identified using thin layer chromatography (TLC) with eluent analytic n-butanol- glacial acetic acid- water (6:1:3). Preparative isolation using thin layer chromatography resulting three bands. Each band was centrifuged to obtain isolates. Physics isolates were analyzing using spectrophotometer UV Vis and chemically using color test (shift reagent). UV Vis spectrum results with shift reagent from isolates 1, suspected as isoflavone compound with OH groups in position 6,7,4 and OH groups in O- ring A, in isolates 2 was not flavonoid compound and predicted as other polyphenolic compound and in isolates 3 suspected of flavone compound with OH groups in position 5,6,7 and OH groups in O-ring A

Zwitterionic sulfonates as m/z shift reagents for 5-methylcytosine detection in deoxyribonucleic acids (DNA) using flow injection analysis and electrospray ionization mass spectrometry.

5-Methylcytosine (5-MC) is an important epigenetic modification of DNA. Abnormally high concentrations of this substance appear because of the hypermethylation of cytosine. Therefore, the measurement of the quantity of this compound in mammals is of great importance. Recently, we reported that several imidazolium-based zwitterionic sulfonates form complexes with 5-MC in solution, which can be studied by electrospray ionisation mass spectrometry (ESI-MS). It is shown in this paper that such an association can be utilised for the detection of 5-MC in a DNA sample using high-throughput a flow injection analysis ESI-MS method. A variety of the sulfonate zwitterions have been tested as m/z shift reagents to increase the selectivity of the analysis. It is shown that either of the zwitterions can be used without the loss of sensitivity. The performance of the method was tested in terms of linearity range, sensitivity, intra- and between-day precision and accuracy, matrix effect and carryover. The method described is characterised by simplicity, a good limit of quantitation (1 pg injected) and low run times (at least 50 injections per hour). In addition, high-performance liquid chromatography and tandem mass spectrometry are not required. The possibility exists to widen the scope of the method to other amidine-containing compounds present in more complicated matrices.

Multiple quantum filtered 23Na NMR in the Langendorff perfused mouse heart: Ratio of triple/double quantum filtered signals correlates with [Na

We investigate the potential of multiple quantum filtered (MQF) 23Na NMR to probe intracellular [Na]i in the Langendorff perfused mouse heart. In the presence of Tm(DOTP) shift reagent the triple quantum filtered (TQF) signal originated largely from the intracellular sodium pool with a 32±6% contribution of the total TQF signal arising from extracellular sodium, whilst the rank 2 double-quantum filtered signal (DQF), acquired with a 54.7° flip-angle pulse, originated exclusively from the extracellular sodium pool. Given the different cellular origins of the 23Na MQF signals we propose that the TQF/DQF ratio can be used as a semi-quantitative measure of [Na]i in the mouse heart. We demonstrate a good correlation of this ratio with [Na]i measured with shift reagent at baseline and under conditions of elevated [Na]i. We compare the measurements of [Na]i using both shift reagent and TQF/DQF ratio in a cohort of wild type mouse hearts and in a transgenic PLM3SA mouse expressing a non-phosphorylatable form of phospholemman, showing a modest but measurable elevation of baseline [Na]i. MQF filtered 23Na NMR is a potentially useful tool for studying normal and pathophysiological changes in [Na]i, particularly in transgenic mouse models with altered Na regulation.

Catalytic Asymmetric Arylation of α-Aryl-α-diazoacetates with Aniline Derivatives.

The asymmetric arylation of diazo compounds with aniline derivatives cooperatively catalyzed by an achiral dirhodium complex and a chiral spiro phosphoric acid is reported. The reaction provides a new method for the facile synthesis of α-diarylacetates, versatile building blocks with a diaryl tertiary chiral center, in good yields (up to 95%) with high enantioselectivities (up to 97% ee). Preliminary mechanistic studies suggest that the arylation reaction proceeds via a stepwise process, in which the enantioselectivity is controlled by a chiral spiro phosphoric acid-promoted proton shift in a zwitterionic intermediate. This work represents the first asymmetric intermolecular C(sp(2))-H bond insertion reaction with arenes.

Precise Determination of Enantiomeric Excess by a Sensitivity Enhanced Two-Dimensional Band-Selective Pure-Shift NMR.

Unambiguous identification and precise quantification of enantiomers in chiral mixtures is crucial for enantiomer specific synthesis as well as chemical analysis. The task is often challenging for mixtures with high enantiomeric excess and for complex molecules with strong (1)H-(1)H scalar (J) coupling network. The recent advancements in (1)H-(1)H decoupling strategies to suppress the J-interactions offered new possibilities for NMR based unambiguous discrimination and quantification enantiomers. Herein, we discuss a high resolution two-dimensional pure-shift zCOSY NMR method with homonuclear band-selective decoupling in both the F1 and F2 dimensions (F1F2-HOBS-zCOSY). This advanced method shows a sharp improvement in resolution over the other COSY methods and also eliminates the problems associated with the overlapping decoupling sidebands. The efficacy of this method has been exploited for precise quantification of enantiomeric excess (ee) ratio (R/S) up to 99:1 in the presence of very low concentrations of chiral lanthanide shift reagents (CLSR) or chiral solvating agents (CSA). The F1F2-HOBS-zCOSY is simple and can be easily implemented on any modern NMR spectrometers, as a routine analytical tool.

Synthesis and conformational studies of calixarene analogue chiral [3.3.1]metacyclophanes

Trihydroxy[3.3.1]metacyclophane, which can be regarded as an unsymmetrical or incomplete “homocalix[3]arene”, has been prepared from trimethoxy[3.3.1]metacyclophane by demethylation with trimethylsilyl iodide in MeCN. Di-O-methylation at the lower rim of trihydroxy[3.3.1]metacyclophane in the presence of K2CO3 in acetone afforded a novel, inherently chiral calixarene–analogue, namely a macrocyclic [3.3.1]metacyclophane, possessing C1 symmetry. The inherent chirality of the two conformers was characterized by 1H NMR spectroscopy by addition of an excess of Pirkle's chiral shift reagent [(S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol], which caused a splitting of the OMe group and AB patterns corresponding to the methylene protons.

Simple Resolution of Enantiomeric NMR Signals of α-Amino Acids by Using Samarium(III) Nitrate With L-Tartarate.

Readily available L-tartaric acid, which is a bidentate ligand with two chiral centers forming a seven-membered chelate ring, was applied to the chiral ligand for the chiral nuclear magnetic resonance (NMR) shift reagent of samarium(III) formed in situ. This simple method does not cause serious signal broadening in the high magnetic field. Enantiomeric (13)C and (1)H NMR signals and enantiotopic (1)H NMR signals of α-amino acids were successfully resolved at pH 8.0 and the 1:3 molar ratio of Sm(NO3)3:L-tartaric acid. It is elucidated that the enantiomeric signal resolution is attributed to the anisotropic magnetic environment for the enantiomers induced by the chiral L-tartarato samarium(III) complex rather than differences in stability of the diastereomeric substrate adducts. The present (13)C NMR signal resolution was also effective for the practical simultaneous analysis of plural kinds of DL-amino acids.

Isolation and Characterization of Scopoletin from The Bark of fagraea ceilanica thumb and Antioxidants Tests

Have done the isolation scopoletin compound from the bark of fagraea ceilanica Thunb by maceration method using n-hexane, ethyl acetate and methanol. Column chromatography with silica gel used for the isolation of the ethyl acetate extract fraction with a mixture of n-hexane and ethyl acetate as the mobile phase in the SGP (step Gradient Polarity). This way produces a dark yellow crystals (26 mg) with a melting point = 205-207 ° C. TLC (Thin Layer Chromatography) were eluted using a mixture of n-hexane: ethyl acetate (7: 3) gives (Rf 0.42). Based on the UV spectrum, shift reagents, IR spectrum and melting point of this compound compared with standard scopoletin showed that the isolated compounds are the same compound or isolated compound is scopoletin. The results of antioxidant test with DPPH of isolated compounds as weak antioxidants with IC 50 = 358.71 mg / L.