Shift Reagent Research Articles

Compartmentalized agents: A powerful strategy for enhancing the detection sensitivity of chemical exchange saturation transfer contrast.

Since the very beginnings of the chemical exchange saturation transfer (CEST) technique, poor overall sensitivity has appeared to be one of its strongest limitations for future applications. Research has therefore focused on designing systems, such as supramolecular and nanosized agents, that contain a high number of magnetically equivalent mobile spins. However, the number of mobile spins offered by these systems is still limited by their composition and surface/volume ratio. The design of compartmentalized agents, that is, systems where an aqueous inner core is separated from the MRI-detected bulk pool via a semipermeable barrier/membrane, is very much a step forward for the technique. These vesicular systems can (i) act as biocompatible and versatile carriers for dia-, para-, and hetero-nuclear CEST probes, thus offering new application options; and (ii) act as CEST probes themselves via the encapsulation of a suitable agent (e.g., a paramagnetic shift reagent) that can change the resonance frequency of the spin pool in the inner compartment only. LipoCEST agents were the pioneers in the latter category, as they are able to grant picomolar sensitivity (in terms of nanoparticle concentration), and paved the way for new applications for CEST agents, especially in the theranostic research area. The use of larger, natural vesicular systems, such as yeasts and cells, in which the huge number of intravesicular spins lowers the detection threshold to a femtomolar limit, is a further step forward in the development of compartmentalized CEST agents. Finally, interesting combinations of nanovesicular and cellular compartmentalized systems have been proposed, thus highlighting how the approach has the potential to drive CEST agents towards completing their journey to mature clinical translation.

Flavonoid Compounds of the Catechin from Wungu (Graptophyllum pictum (L.) Griff) Leaves and the Sun Protecting Factor Value

The flavonoid content in wungu (Graptophyllum pictum (L.) Griff.) leaves has the potential as a sunscreen. The study aims to identify isolates of flavonoid compounds from wungu leaves and determine the SPF value. Steps are followed by extraction, fractionation, phytochemical test, separation by chromatography, identification, and SPF test. Extraction was carried out with methanol, followed by fractionation with n-hexane and dichloromethane. Dichloromethane fraction was chosen to proceed to the separation step because the results of the phytochemical test showed a vigorous color intensity for the content of flavonoids. The isolate (3.6 mg; dark green; amorphous; mp. 132-136 °C) was identified using a UV-Vis spectrophotometer using methanol as a solvent with a shift reagent NaOH, AlCl3, and a mixture of concentrated AlCl3 and HCl. Based on the UV-Vis spectra, the isolate was predicted to be flavonoid compounds belonging to the catechin group, which have a hydroxyl group at positions C-3, C-7, and do not have an ortho-hydroxy group in ring B. The SPF value of the isolate of 2.3244 at 100 ppm was determined in vitro and calculated by the Qian equation. Therefore, isolate was categorized as sunscreens that provided minimal protection

C1-Symmetric Aza-Crown Ethers as Chiral Shift Agents for Amines and Amino Acid Derivatives

C1-Symmetric Aza-Crown Ethers as Chiral Shift Agents for Amines and Amino Acid Derivatives

Experimentally probing the chiral recognition mechanism of 1,1′-bi-2-naphthol on a nitrogen enriched chiral metal-organic framework

In this article, a micropore CMOF structure with abundant nitrogen species, D-His-ZIF-L (DHZL), was synthesized in water according to the reference with a modification. The performance of DHZL was verified by enantioselective capture of S-1,1′-bi-2-naphthol (S-BINOL), with an enantiomeric excess (ee) value of 60.5% under optimal conditions. To experimentally elucidate the chiral recognition mechanism, the chemical shifts of carbon and nitrogen signals were investigated on the basis of CP MAS NMR spectroscopy by using DHZL (200 mg) with R/S-BINOL of 750 μg mL−1 in CH3CN at room temperature, in which DHZL acts as the chiral shift reagent. The peaks corresponding to the chiral carbon and one imidazole ring carbon resonances in the D-histidine moiety of DHZL exhibit obvious upfield and downfield shifts in the presence of S-BINOL, respectively, indicating that the the strong hydrogen bonding and π-π interactions existed. Clear nitrogen splitting further indicates the hydrogen-bond interaction site between the hydroxyl of the optical S-isomer and the amino of D-histidine in the chiral framework. In addition, the positive shift in the N 1 s peak of DHZL by X-ray photoelectron spectroscopy (XPS) analysis was also proved the described observations when loaded with S-BINOL in contrast with R-one. Furthermore, a control experiment was performed to identify the essential features of the chiral microenvironment in DHZL. Based on these results above, the chiral recognition mechanism was experimentally determined.

Detection of glucose-derived d- and l-lactate in cancer cells by the use of a chiral NMR shift reagent

BackgroundExcessive lactate production, a hallmark of cancer, is largely formed by the reduction of pyruvate via lactate dehydrogenase (LDH) to l-lactate. Although d-lactate can also be produced from glucose via the methylglyoxal pathway in small amounts, less is known about the amount of d-lactate produced in cancer cells. Since the stereoisomers of lactate cannot be distinguished by conventional 1H NMR spectroscopy, a chiral NMR shift reagent was used to fully resolve the 1H NMR resonances of d- and l-lactate.MethodsThe production of l-lactate from glucose and d-lactate from methylglyoxal was first demonstrated in freshly isolated red blood cells using the chiral NMR shift reagent, YbDO3A-trisamide. Then, two different cell lines with high GLO1 expression (H1648 and H 1395) were selected from a panel of over 80 well-characterized human NSCLC cell lines, grown to confluence in standard tissue culture media, washed with phosphate-buffered saline, and exposed to glucose in a buffer for 4 h. After 4 h, a small volume of extracellular fluid was collected and mixed with YbDO3A-trisamide for analysis by 1H NMR spectroscopy.ResultsA suspension of freshly isolated red blood cells exposed to 5mM glucose produced l-lactate as expected but very little d-lactate. To evaluate the utility of the chiral NMR shift reagent, methylglyoxal was then added to red cells along with glucose to stimulate the production of d-lactate via the glyoxalate pathway. In this case, both d-lactate and l-lactate were produced and their NMR chemical shifts assigned. NSCLC cell lines with different expression levels of GLO1 produced both l- and d-lactate after incubation with glucose and glutamine alone. A GLO1-deleted parental cell line (3553T3) showed no production of d-lactate from glucose while re-expression of GLO1 resulted in higher production of d-lactate.ConclusionsThe shift-reagent-aided NMR technique demonstrates that d-lactate is produced from glucose in NSCLC cells via the methylglyoxal pathway. The biological role of d-lactate is uncertain but a convenient method for monitoring d-lactate production could provide new insights into the biological roles of d- versus l-lactate in cancer metabolism.

Immutable quantized transport in Floquet chains

We show how quantized transport can be realized in Floquet chains through encapsulation of a chiral or helical shift. The resulting transport is immutable rather than topological in the sense that it neither requires a band gap nor is affected by arbitrarily strong perturbations. Transport is still characterized by topological quantities but encapsulation of the shift prevents topological phase transitions. To explore immutable transport we introduce the concept of a shiftbox, explain the relevant topological quantities both for momentum-space dispersions and real-space transport, and study model systems of Floquet chains with strictly quantized chiral and helical transport. Natural platforms for the experimental investigation of these scenarios are photonic Floquet chains constructed in waveguide arrays, as well as topolectrical or mechanical systems.

Intrinsic anisotropy parameters of a series of lanthanoid complexes deliver new insights into the structure-magnetism relationship

Intrinsic anisotropy parameters of a series of lanthanoid complexes deliver new insights into the structure-magnetism relationship

Photo-induced electron transfer of [C60 + Abacavir] nano-complex and feasibility of C60 fullerene application as a chemical shift reagent: a DFT/TD-DFT insights

Photo-induced electron transfer of [C60 + Abacavir] nano-complex and feasibility of C60 fullerene application as a chemical shift reagent: a DFT/TD-DFT insights

Separations of Carbohydrates with Noncovalent Shift Reagents by Frequency-Modulated Ion Mobility-Orbitrap Mass Spectrometry.

An increased focus on characterizing the structural heterogeneity of carbohydrates has been driven by their many significant roles in extant life and potential roles in chemical evolution and the origin of life. In this work, multiplexed drift tube ion mobility-Orbitrap mass spectrometry methods were developed to analyze mixtures of disaccharides modified with noncovalent shift reagents. Since traditional coupling of atmospheric pressure drift tube ion mobility cells with Orbitrap mass analyzers suffers from low duty cycles (<0.1%), a frequency modulation scheme was applied to improve the signal-to-noise ratios (SNR). Several parameters such as the resolution setting and maximum injection time of the Orbitrap analyzer and the magnitude and duration of the frequency sweep were investigated for their impact on the sensitivity gains and resolution of disaccharide-shift reagent adducts. The sweep time and disaccharide concentration had a positive correlation with SNR. The magnitude of the frequency sweep had a negative correlation with SNR. However, increasing the frequency sweep improved the resolution of mixtures of disaccharide analytes. Application of frequency-modulated ion mobility-Orbitrap mass spectrometry to four noncovalently modified glucose dimers allowed for the differentiation of three out of these four analytes.

Quantum sensing protocol for motionally chiral Rydberg atoms

A quantum sensing protocol is proposed for demonstrating the motion-induced chirality of circularly polarised Rydberg atoms. To this end, a cloud of Rydberg atoms is dressed by a bichromatic light field. This allows to exploit the long-lived ground states for implementing a Ramsey interferometer in conjunction with a spin echo pulse sequence for refocussing achiral interactions. Optimal parameters for the dressing lasers are identified. Combining a circularly polarised dipole transition in the Rydberg atom with atomic centre-of-mass motion, the system becomes chiral. The resulting discriminatory chiral energy shifts induced by a chiral mirror are estimated using a macroscopic quantum electrodynamics approach. The presented quantum sensing protocol will also provide an indirect proof for Casimir–Polder quantum friction.

Enantioselective Recognition of Racemic Amino Alcohols in Aqueous Solution by Chiral Metal-Oxide Keplerate {Mo132 } Cluster Capsules.

Determining the relative configuration or enantiomeric excess of a substance may be achieved using NMR spectroscopy by employing chiral shift reagents (CSRs). Such reagents interact noncovalently with the chiral solute, resulting in each chiral form experiencing different magnetic anisotropy; this is then reflected in their NMR spectra. The Keplerate polyoxometalate (POM) is a molybdenum‐based, water‐soluble, discrete inorganic structure with a pore‐accessible inner cavity, decorated by differentiable ligands. Through ligand exchange from the self‐assembled nanostructure, a set of chiral Keplerate host molecules has been synthesised. By exploiting the interactions of analyte molecules at the surface pores, the relative configuration of chiral amino alcohol guests (phenylalaninol and 2‐amino‐1‐phenylethanol) in aqueous solvent was establish and their enantiomeric excess was determined by 1H NMR using shifts of ΔΔδ=0.06 ppm. The use of POMs as chiral shift reagents represents an application of a class that is yet to be well established and opens avenues into aqueous host‐guest chemistry with self‐assembled recognition agents.

Inhibition of α-glucosidase by flavonoids of Cymbopogon citratus (DC) Stapf

Leaves extracts from Cymbopogon citratus (DC) Stapf. are widely used in traditional medicine exhibiting several in vivo biological activities, including antidiabetic. Several flavonoids, including aglycones and glycosides, were reported in this plant and previous studies suggested that flavonoids may interact with targets related to diabetes. Evaluated the hypoglycemic activity of C. citratus flavonoids through α-glucosidase inhibition and assess the structure-activity relationship using molecular docking studies. An infusion of C. citratus leaves and its flavonoid-rich fraction were prepared. Five flavonoids from this fraction were isolated and structurally characterized by UV spectral analysis with shift reagents, HPLC-PDA-ESI/MSn and 1H NMR. The antidiabetic potential of C. citratus infusion, its flavonoid-rich fraction, glycosylated flavonoids and aglycones was evaluated trough the in vitro inhibition of yeast α-glucosidase. Posteriorly, molecular docking of the tested flavonoids was performed to investigate its possible interactions with the α-glucosidase pocket. The infusion of C. citratus, its flavonoid-rich fraction, luteolin and five flavone glycosides namely, luteolin 6-C-β-glucopyranoside (isoorientin), luteolin 7-O-neohesperidoside (ionicerin), luteolin 7-O-β-glucopyranoside (cynaroside), Luteolin 2″-O-rhamnosyl-C-(6-deoxy-ribo-hexos-3-ulosyl) (cassiaoccidentalin B), luteolin 6-C-α-arabinofuranosil-(1→2)-α-L-rhamnopyranoside (kurilesin A) showed higher inhibitory activity than the reference drug. This activity increased by the addition of a sugar moiety. However, the di-glycosides were less active than mono-glycosides. The docking studies showed interactions of sugar moieties and A or B rings with the catalytic pocket mainly through hydrogen bonds. Our results corroborate the potential of C. citratus as a medicinal plant for the treatment of diabetes and revealed that its flavonoid glycosides has hypoglycemic effect and can be explored as drug candidates to act as α-glucosidase inhibitors in the treatment of diabetes.

Probing the Chiral Domains and Excitonic States in Individual WS2 Tubes by Second-Harmonic Generation.

Distinct from carbon nanotubes, transition-metal dichalcogenide (TMD) nanotubes are noncentrosymmetric and polar and can exhibit some intriguing phenomena such as nonreciprocal superconductivity, chiral shift current, bulk photovoltaic effect, and exciton-polaritons. However, basic characterizations of individual TMD nanotubes are still quite limited, and much remains unclear about their structural chirality and electronic properties. Here we report an optical second-harmonic generation (SHG) study on multiwalled WS2 nanotubes on a single-tube level. As it is highly sensitive to the crystallographic symmetry, SHG microscopy unveiled multiple structural domains within a single WS2 nanotube, which are otherwise hidden under conventional white-light optical microscopy. Moreover, the polarization-resolved SHG anisotropy patterns revealed that different domains on the same tube can be of different chirality. In addition, we observed the excitonic states of individual WS2 nanotubes via SHG excitation spectroscopy, which were otherwise difficult to acquire due to the indirect band gap of the material.

Absolute Configuration of In Situ Crystallized (+)-γ-Decalactone

Knowledge about the absolute configuration of small bioactive organic molecules is essential in pharmaceutical research because enantiomers can exhibit considerably different effects on living organisms. X-ray crystallography enables chemists to determine the absolute configuration of an enantiopure compound due to anomalous dispersion. Here, we present the determination of the absolute configuration of the flavoring agent (+)-γ-decalactone, which is liquid under ambient conditions. Single crystals were grown from the liquid in a glass capillary by in situ cryo-crystallization. Diffraction data collection was performed using Cu-Kα radiation. The absolute configuration was confirmed. The molecule consists of a linear aliphatic non-polar backbone and a polar lactone head. In the solid state, layers of polar and non-polar sections of the molecule alternating along the c-axis of the unit cell are observed. In favorable cases, this method of absolute configuration determination of pure liquid (bioactive) agents or liquid products from asymmetric catalysis is a convenient alternative to conventional methods of absolute structure determination, such as optical rotatory dispersion, vibrational circular dichroism, ultraviolet-visible spectroscopy, use of chiral shift reagents in proton NMR and Coulomb explosion imaging.

Synthetic strategies towards chiral coordination polymers

• Chiral coordination polymers can be synthesised via direct or indirect methods. • Indirect methods include spontaneous resolution, chiral templating and induction. • Ligands with point chirality can be derived from various chiral pool molecules. • Other coordination polymers are built from ligands with axial or planar chirality. • Post-synthetic modification can be used to impart or unveil chirality in frameworks. Chiral coordination polymers and porous chiral MOFs have great potential as agents for enantioselective separations, sensing, and catalysis due to their well-structured internal chiral cavities. They also have physical properties that may be exploited, such as non-linear optical activity, ferroelectrics, magnetochiral dichroism, and use as chemical shift reagents. There are many ways in which chiral coordination polymers can be synthesised and the file has grown tremendously over the past two decades. In this review, we will discuss some of the main synthetic approaches that have been taken towards this fascinating class of materials. The main focus will be placed on synthetic approaches using enantiopure ligands, the route that is most likely to yield homochiral network solids. We will highlight the applications of many examples, noting how the design of the frameworks influences their application. Whilst this is a mature field, there still lies huge potential for functional chiral materials, and we aim to demonstrate areas that are ripe for exploration.

Gravity loop integrands from the ultraviolet

We demonstrate that loop integrands of (super-)gravity scattering amplitudes possess surprising properties in the ultraviolet (UV) region. In particular, we study the scaling of multi-particle unitarity cuts for asymptotically large momenta and expose an improved UV behavior of four-dimensional cuts through seven loops as compared to standard expectations. For N=8 supergravity, we show that the improved large momentum scaling combined with the behavior of the integrand under BCFW deformations of external kinematics uniquely fixes the loop integrands in a number of non-trivial cases. In the integrand construction, all scaling conditions are homogeneous. Therefore, the only required information about the amplitude is its vanishing at particular points in momentum space. This homogeneous construction gives indirect evidence for a new geometric picture for graviton amplitudes similar to the one found for planar N=4 super Yang-Mills theory. We also show how the behavior at infinity is related to the scaling of tree-level amplitudes under certain multi-line chiral shifts which can be used to construct new recursion relations.

Electron paramagnetic resonance of lanthanides.

Many applications of lanthanides exploit their electron spin relaxation properties. Double electron-electron measurements of distances are possible because of the relatively long relaxation times of Gd3+. Relaxation enhancement measurements of distance are possible because of the much shorter relaxation times of other lanthanides. Magnetic resonance imaging contrast agents use the long relaxation time of the S-state Gd3+ ion, and NMR shift reagents use the fast relaxation of selected other lanthanides. Other than Gd3+ and the isoelectronic Eu2+ ion, spin relaxation of the lanthanides is so fast that their EPR spectra can be observed only in the liquid helium temperature range. In this chapter the EPR properties of each of the lanthanides is briefly summarized, with an emphasis on electron spin relaxation.

Exchange-modified DOSY experiments. the use of chiral solvating agents and lanthanide shift reagents as matrices

(S)-BINOL and Eu(fod)3 were tried as matrices to improve DOSY performance and Dt and MW prediction power on small organic molecules.

CHARACTERIZATION OF FLAVONOIDS ISOLATED FROM Trigonellafoenum-graecum USING UV SHIFT REAGENT

The biggest challenge in utilizing plant secondary metabolites lies in extraction, isolation and characterization using available analytical techniques. UV absorption is an excellent technique for the identification and characterization of phenolic compounds. Phyto compounds characterization using UV absorption spectrum is very helpful and it gives quick results which can be interpreted easily, wherein preparation of the sample for analysis involves no difficulty. In this study, we have identified and characterized 2 flavonoids, kaempferol 3-o rutinoside and chrysoreol using UV shift reagents, isolated from Trigonella foenumgraecum methanolic seed extract. The same was confirmed by reference Mass and NMR spectral results reported in the literature. Characterization using UV-visible spectrometry is a powerful technique that can be employed for phytochemical identification and characterization purposes with great leverage when sample isolated is less.

Application of Lanthanide Shift Reagent to the 1H-NMR Assignments of Acridone Alkaloids.

This study investigates the application of the paramagnetic shift reagent tris(dipivaloylmethanato)-europium(III) in NMR spectral studies of permethoxyacridone alkaloids (1–3) and pyranoacridone alkaloids (4–6). The induced chemical shifts (∆δ) of all protons were observed for the same molecule, and were compared to deduce the positions resulting from the distance nearby the Eu(dpm)3. Assignment of the H-2, H-4 and H-8 of polysubstituted acridones could be distinguished based on the least-squares method of lanthanide-induced shifts plotted against the mole ratios of Eu(dpm)3 to the substrate. The developed method is not only potentially useful for determining the planar structures of polysubstituted compounds, such as acridones, anthraquinones, xanthones, flavonoids, and phenanthrenes, but also applicable for their stereochemistry.