Ion-shift reagent binding energy and the shift-mass correlation in ion mobility spectrometry

Ion mobility spectrometry is widely used for the detection of illegal substances and explosives in airports, ports, custom, some stations and many other important places. This task is usually complicated by false positives caused by overlapping the target peaks with that of interferents, commonly associated with samples of interest. Shift reagents (SR) are species that selectively change ion mobilities through adduction with analyte ions when they are introduced in IMS instruments. This characteristic can be used to discriminate false positives because the interferents and illegal substances respond differently to SR depending on the structure and size of analytes and their interaction energy with SR. This study demonstrates that ion mobility shifts upon introduction of SR depend, not only on the ion masses, but on the interaction energies of the ion:SR adducts. In this study, we introduced five different SRs using ESI-IMS-MS to study the effect of the interaction energy and size on mobility shifts. The mobility shifts showed a decreasing trend as the molecular weight increased for the series of compounds ethanolamine, valinol, serine, threonine, phenylalanine, tyrosine, tributylamine, tryptophan, desipramine, and tribenzylamine. It was proved that the decreasing trend was partially due to the inverse relation between the mobility and drift time and hence, the shift in drift time better reflects the pure effect of SR on the mobility of analytes. Yet the drift time shift exhibited a mild decrease with the mass of ions. Valinol pulled out from this trend because it had a low binding energy interaction with all the SR and, consequently, its clusters were short-lived. This short lifetime produced fewer collisions against the buffer gas and a drift time shorter compared to those of ions of similar molecular weight. Analyte ion:SR interactions were calculated using Gaussian. IMS with the introduction of SR could be the choice for the free-interferents detection of illegal drugs, explosives, and biological and warfare agents. The suppression of false positives could facilitate the transit of passengers and cargos, rise the confiscation of illicit substances, and save money and distresses due to needless delays. Keywords: Adduction, ion mobility spectrometry, mass spectrometry, shift reagent, valinol, buffer gas modifier

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

Background Excessive 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. Methods The 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. Results A 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. Conclusions The 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.

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.

Structure of micelle bound cationic peptides by NMR spectroscopy using a lanthanide shift reagent

[Tm(DPA)3]3− generates paramagnetic, dispersed 2D transferred NOESY spectra for high-resolution structures of cationic peptides in the LPS micelle bound state.

Enantioselective Michael Addition: An Experimental Introduction to Asymmetric Synthesis

<p> We adapted a classical asymmetric Michael addition for a 1-day experimental session (6-8 hrs) for third or fourth-year undergraduate students. The experiment follows up three steps : synthesis of a chiral Lewis Acid, LiAl(BINOL)₂, then its use as a catalyst in the Michael addition of diethyl malonate on cyclopentenone, followed by purification through column chromatography on silica gel. The desired product can be fully characterized by 1D and 2D NMR experiments and IR spectroscopy. The enantiomeric excess can be determined by polarimetry and ¹H NMR using chiral lanthanide shift reagent Eu(hfc)₃.</p>

Enantioselective Michael Addition: An Experimental Introduction to Asymmetric Synthesis

<p> We adapted a classical asymmetric Michael addition for a 1-day experimental session (6-8 hrs) for third or fourth-year undergraduate students. The experiment follows up three steps : synthesis of a chiral Lewis Acid, LiAl(BINOL)₂, then its use as a catalyst in the Michael addition of diethyl malonate on cyclopentenone, followed by purification through column chromatography on silica gel. The desired product can be fully characterized by 1D and 2D NMR experiments and IR spectroscopy. The enantiomeric excess can be determined by polarimetry and ¹H NMR using chiral lanthanide shift reagent Eu(hfc)₃.</p>

The use of tris (tetraphenylimidodiphosphinate) of praseodymium chemical shift reagent in proton NMR for the evaluation of the argan oil fatty acids autoxidation and the analysis of the argan pulp fatty acids

Proton NMR is a method of molecular investigation that has its limitations when applied to complex molecules or molecules with many nearly equivalent sites. Previous studies have resorted to the use of paramagnetic chemical shift reagents, having as formula tris (tetraphenylimidodiphosphinate) of lanthanides ln((tpip.)3. The use of reagent Pr(tpip)3 in proton RMN has allowed us to evaluate the autoxidation of fatty acids mixture (stored 6 and 12 months after oil extraction) by the dosage of saturated and unsaturated acids on the one hand, and that of oleic and linoleic acids on the other. We note between 6 and 12 months of storage at 4°C a decrease in the percentage of unsaturated acids (76% to 63%) and an increase in the percentage of saturated acids (24% to 36%). The results show that the oleic acid maintained the same percentage (35%) as it is not easily oxidized whereas, for the linoleic acid, we observe a decrease in percentage from 22.5% to 18.5% (slow autoxidation at 4°C). We also used this NMR method for the analysis of the argan pulp fatty part. The GC analysis shows that it contains very few unsaturated fatty acids and that the main fatty acids are myristic (C14:0) and palmitic (C16:0) acids. The proton NMR with Pr(tpip)3 allowed us to confirm these results. This method that does not require derivation has proven to be interesting, simple and efficient.

The use of tris (tetraphenylimidodiphosphinate) of praseodymium chemical shift reagent in proton NMR for the evaluation of the argan oil fatty acids autoxidation and the analysis of the argan pulp fatty acids

<p>Proton NMR is a method of molecular investigation that has its limitations when applied to complex molecules or molecules with many nearly equivalent sites. Previous studies have resorted to the use of paramagnetic chemical shift reagents, having as formula tris (tetraphenylimidodiphosphinate) of lanthanides ln((tpip.)3.<strong> </strong>The use of reagent Pr(tpip)3 in proton RMN has allowed us to evaluate the autoxidation of fatty acids mixture (stored 6 and 12 months after oil extraction) by the dosage of saturated and unsaturated acids on the one hand, and that of oleic and linoleic acids on the other. We note between 6 and 12 months of storage at 4°C a decrease in the percentage of unsaturated acids (76% to 63%) and an increase in the percentage of saturated acids (24% to 36%). The results show that the oleic acid maintained the same percentage (35%) as it is not easily oxidized whereas, for the linoleic acid, we observe a decrease in percentage from 22.5% to 18.5% (slow autoxidation at 4°C). We also used this NMR method for the analysis of the argan pulp fatty part. The GC analysis shows that it contains very few unsaturated fatty acids and that the main fatty acids are myristic (C14:0) and palmitic (C16:0) acids. The proton NMR with Pr(tpip)3 allowed us to confirm these results. This method that does not require derivation has proven to be interesting, simple and efficient.</p>