Shift Reagent Research Articles

Chiral shift symmetries as an infinite tower of subleading super-shift symmetries

Chiral shift symmetries of the massless free bosons in two dimensions are global symmetries that are somewhat similar to asymptotic symmetries. They are most transparent in double-null coordinates where they are parametrized by two functions of one variable. In BMS-type coordinates, half of them appear as an infinite tower of sub-leading super-shift symmetries.

Leveraging High-Resolution Ion Mobility-Mass Spectrometry for Cyclic Peptide Soft Spot Identification.

Cyclic peptides are an important class of molecules that gained significant attention in the field of drug discovery due to their unique pharmacological characteristics and enhanced proteolytic stability. Yet, gastrointestinal degradation remains a major hurdle in the discovery of orally bioavailable cyclic peptides. Soft spot identification (SSID) of the regions in the cyclic peptide sequence susceptible to amide hydrolysis by proteases is used in the discovery stage to guide medicinal chemistry design. SSID can be an arduous task, traditionally performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), often resulting in complex and time-consuming manual analysis, particularly when isomeric linear peptide metabolites chromatographically coelute. Here, we present an alternative orthogonal approach that entails a high-resolution ion mobility (HRIM) system based on Structures for Lossless Ion Manipulation (SLIM) technology interfaced with quadrupole time-of-flight (QTOF) mass spectrometry to address some of the challenges associated with SSID. Two strategies were used to resolve linear isomeric peptide metabolites: labeled and label-free, both utilizing the HRIM platform. The label-free strategy leverages negative polarity to ionize the isomers which achieves better separation of the gas phase ions in the ion mobility (IM) dimension as compared to positive polarity, which is a more conventional approach when studying proteins and peptides. The second approach uses an isotope-labeled dimethyl tag on the terminal amine group, acting as a "shift reagent" to influence the mobility of isomers in the positive mode. This method resulted in baseline separation for the isomers of interest and produced unique product ions in the fragmentation spectra for unambiguous soft spot identification. Both label-free and labeled strategies demonstrated the ability to solve the challenges associated with SSID for cyclic peptides.

Tris-Silanide f-Block Complexes: Insights into Paramagnetic Influence on NMR Chemical Shifts.

The paramagnetism of f-block ions has been exploited in chiral shift reagents and magnetic resonance imaging, but these applications tend to focus on 1H NMR shifts as paramagnetic broadening makes less sensitive nuclei more difficult to study. Here we report a solution and solid-state (ss) 29Si NMR study of an isostructural series of locally D 3h -symmetric early f-block metal(III) tris-hypersilanide complexes, [M{Si(SiMe3)3}3(THF)2] (1-M; M = La, Ce, Pr, Nd, U); 1-M were also characterized by single crystal and powder X-ray diffraction, EPR, ATR-IR, and UV-vis-NIR spectroscopies, SQUID magnetometry, and elemental analysis. Only one SiMe3 signal was observed in the 29Si ssNMR spectra of 1-M, while two SiMe3 signals were seen in solution 29Si NMR spectra of 1-La and 1-Ce. This is attributed to dynamic averaging of the SiMe3 groups in 1-M in the solid state due to free rotation of the M-Si bonds and dissociation of THF from 1-M in solution to give the locally C 3v -symmetric complexes [M{Si(SiMe3)3}3(THF) n ] (n = 0 or 1), which show restricted rotation of M-Si bonds on the NMR time scale. Density functional theory and complete active space self-consistent field spin-orbit calculations were performed on 1-M and desolvated solution species to model paramagnetic NMR shifts. We find excellent agreement of experimental 29Si NMR data for diamagnetic 1-La, suggesting n = 1 in solution and reasonable agreement of calculated paramagnetic shifts of SiMe3 groups for 1-M (M = Pr and Nd); the NMR shifts for metal-bound 29Si nuclei could only be reproduced for diamagnetic 1-La, showing the current limitations of pNMR calculations for larger nuclei.

Quantum Mechanical Quantitative Nuclear Magnetic Resonance Enables Digital Reference Standards at All Magnetic Fields and Enhances qNMR Sustainability.

Quantum mechanics (QM)-driven 1H iterative functionalized spin analysis produces HifSA profiles, which encode the complete 1H spin parameters ("nuclear genotype") of analytes of interest. HifSA profiles enable the establishment of digital reference standards (dRS) that are portable, FAIR (findable - accessible - interoperable - reusable), and fit for the purpose of quantitative 1H NMR (qHNMR) analysis at any magnetic field. This approach enhances the sustainability of analytical standards. Moreover, the analyte-specific complete chemical shift and J-coupling information in HifSA-based dRS enable computational quantitation of substances in mixtures via QM-total-line-shape fitting (QM-qHNMR). We present the proof of concept for HifSA-based dRS by resolving the highly overlapping NMR resonances in the experimental spectra ("nuclear phenotypes") of the diastereomeric mixture of (2RS, 4RS)- and (2RS, 4SR)-difenoconazole (DFZ), a widely used antifouling food additive. The underlying 1H spin parameters are highly conserved in various solvents, are robust against variation in measurement temperature, and work across a wide range of magnetic fields. QM-qHNMR analysis of DFZ samples at 80, 400, 600, and 800 MHz showed high congruence with metrological reference values. Furthermore, this study introduces QM-qHNMR combined with chiral shift reagents for the analysis of all four DFZ stereoisomers: (2R, 4R)-, (2S, 4S)-, (2R, 4S)-, and (2S, 4R)-DFZ to perform chiral qHNMR measurements.

Optimization and Effect of Substituents on the Transformation of 3-(Substituted acetoxy)azetidin-2-ones to Chiral 3-Hydroxyazetidin-2-ones, Molecular Docking and Enantiomeric Excess Determination

Abstract: The enantioselective synthesis of chiral cis-3-hydroxyazetidin-2-ones mediated by Porcine Pancreatic Lipase (PPL) via hydrolysis of cis-3-(chloro acetoxy) azetidin-2-ones in the presence of a phosphate buffer (0.1M, pH = 7.2) in acetonitrile at a temperature range of 25-35 °C was optimized. Under the optimized reaction conditions, the influence of various electron withdrawing/donating/neutral groups on ester functionality of cis-3-(substituted acetoxy)azetidin-2- ones towards hydrolysis was extensively studied, and the bromoacetoxy, propanyloxy, and formyloxy groups provided moderate to good yields of 90%, 91%, and 81%, respectively. Moreover, the chiral cis-3-hydroxyazetidin-2-ones underwent acetylation, and their enantiomeric excess was assessed using the 1H NMR technique, employing chiral shift reagents. To gain insights into the active sites of the biocatalyst, molecular docking studies of compounds 5(a-i) with pancreatic lipase (PDB ID: 1LBS) were carried out. Additionally, the proposed interaction of substituents with the biocatalyst established the absolute stereochemistry of the target chiral cis-3-hydroxyazetidin-2-ones using Seebach's model in comparison to Jone's models.

Abstract 4158: Non-invasive mapping of acidosis and extracellular lactosis for assessing tumor invasion in vivo

Abstract Tumor cells typically display a hyperglycolytic metabolic phenotype characterized by increased lactate production, known as the Warburg effect. This drift in oxidative metabolism often results in a more acidic microenvironment. This adverse microenvironment represents a unique metabolic signature in cancer cells with more invasive phenotypes. However, to date, there are no effective methods available to evaluate cancer progression and metastatic potential in vivo. To bridge this gap, we have developed a molecular imaging technique (CEST-MRI) that can track extracellular pH (pHe; acidoCEST) and extracellular lactate levels (shiftCEST) simultaneously to discern different cancer phenotypes. In this study we have generated and selected in vivo two PyMT derived murine breast cancer cell lines, a parental and a G6 metastatic. We first characterized the cell’s metabolism by analyzing key biomarkers with qPCR, Western Blot and microscopy, and confirmed their distinct metabolic profiles with Seahorse and RNA Sequencing. Notably, the metastatic PyMT exhibited a more active metabolism, aligning with the invasive phenotype observed by spheroid invasion assay. Herein, we combined the injection of iopamidol and shift reagent (SR) to perform quasi-simultaneous acidoCEST and shiftCEST. First, we assessed the approach in vitro by introducing iopamidol and SR into phantoms containing the individual contrast agents, and the combination in pure water and cells supernatants at different pHe and lactate levels. We performed LDH assays to cross-validate the extracellular concentrations and monitored the pH with a micro pH meter (Mettler-Toledo). In vivo, the cells were injected orthotopically in the 4th mammary fat pad of C57BL/6N mice. Hybrid shift/acidoCEST sequences were optimized and acquired following the injection of the iopamidol+SR solution. Preclinical shift/acidoCEST enabled the simultaneous and accurate determination of extracellular acidosis and lactosis, revealing increased acidification in the metastatic models despite lower lactate secretion. Metastatic tumors exhibited a negative correlation between tumor volume and pHe, indicating the significance of acidity in mutagenesis and invasion. In contrast, no correlation was observed for the parental non-metastatic tumor. Additionally, the metastatic tumors had lower levels of lactate than the parental tumors, which could be attributed to their higher mitochondrial activity, reflecting a diverted metabolic fitness. In summary, our study highlights the efficacy of shift/acidoCEST as a reliable method for non-invasive metabolic imaging, enabling the simultaneous detection of extracellular acidity and lactate production by MRI. This research introduces a unique platform for assessing the metabolic aggressiveness of cancer, emphasizing the significance of acidity and lactate production as crucial biomarkers in cancer invasion. Citation Format: Anais Choffart, Remy Chiaffarelli, Max Zimmermann, Laura Kuebler, André Martins. Non-invasive mapping of acidosis and extracellular lactosis for assessing tumor invasion in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4158.

Tuning structural and thermal conductivity of carbon nanotubes under strain effects

Equilibrium molecular dynamics (EMD) computations have been performed to estimate the thermal conductivity (λ) of armchair and chiral single-walled carbon nanotubes (SWCNTs) under the influence of varying axial compressive and tensile strains ±γ(%). For the first time, the present work provides new outcomes of structural behavior of SWCNTs linked through λ, considering the combinations of nanotube length (L), system temperature (T) and effects of varying ±γ(%). A radial distribution function (RDF) test has performed in order to investigate the structure analysis of armchair and chiral SWCNTs with different compressive (−1% – −10%) and tensile (+1% – +10%) strain sequences at the extreme L (= 100 Å and 1900 Å) and T (=300 K). The RDF and visualization tests indicate that both configurations are more tunable under tensile strain but the buckling processes of armchair SWCNTs are less evident as compared to chiral configurations. The simulation data shows that the λ(T, L) increases as L extends and it also confirmed through slight increase in RDF peaks, while the λ(T, L) of chiral SWCNTs is high compared to armchair SWCNTs for a complete range of T at L (= 100 Å and 1900 Å). However, the calculations indicate that the delta change in λ(T, L) of armchair SWCNTs is more than the chiral one, as expected. The simulation data demonstrates that the positions of the highest and lowest values of the thermal conductivity of the chiral SWCNTs shift to a longer L as compared to the armchair SWCNTs. The λ(T, L) of SWCNTs remains high for -γ(%) range at short L (=100 Å) due to less broaden shift in RDF peaks but slightly higher for +γ(%) range at longer L (=1900 Å) due to boarder shift in RDF peaks. Moreover, the present simulation results obtained from EMD approach are found to be in reasonable agreement with those obtained via the previous known numerical results.

Near-extremal limits of warped CFTs

Warped conformal field theories (WCFTs) are two-dimensional non-relativistic systems, with a chiral scaling and shift symmetry. We present a detailed derivation of the near-extremal limit for their torus partition function. This limit requires large values of the central charge, and is only consistent for non-unitary WCFT. We compare our analysis with previous studies of WCFT and its relation to a one-dimensional warped-Schwarzian theory. We discuss different ensembles of warped CFTs and contrast our results with analogous limits in two-dimensional CFTs.

Chiral Pyrrolidinium Ionic Liquids with (-)-Borneol Fragment in the Cation - Synthesis, Physicochemical Properties and Application in Diels-Alder Reaction.

A series of chiral pyrrolidinium salts containing (1S)-endo-(-)-born-2-yloxymethyl substituent in the structure of the cation and six different anions: chloride, tetrafluoroborate [BF₄]¯, hexafluorophosphate [PF₆]¯, trifluoromethanosulfonate [OTf]¯, bis(trifluoromethylsulfonyl)imide [NTf₂]¯, bis(pentafluoroethylsulfonyl)imide [NPf₂]¯and perfluorobutanesulfonate [C₄FS]¯were efficiently prepared and extensively characterized. The enantiomeric purity of them was confirmed by NMR analysis with a chemical shift reagent. All salts were characterized with the specific rotation, the solubility in commonly used solvents, thermal properties, including phase transition temperatures and thermal stability. Salts with [PF₆]¯, [C₄FS]¯, [NTf₂]¯and [NPf₂]¯anions were classified as chiral ionic liquids (CILs). Moreover, salts with [NTf₂]¯and [NPf₂]¯anions were in the liquid state at room temperature and below. Therefore, the refractive index, density and dynamic viscosity, the surface tension and the contact angle on three different surfaces were also measured for them. Additionally, these chiral ionic liquids were tested as solvents in Diels-Alder reaction.

Traceless Chiral Shift Reagent Based on Nonbonding Interaction with Single-Handed Helical Poly(quinoxaline-2,3-diyl).

Single-handed poly(quinoxaline-2,3-diyl)s (PQX) have been found to serve as a new chiral shift reagent (CSR) for determining the enantiomeric ratio by NMR. Even though there is no specific binding site in PQX, its nonbonding interaction with chiral analytes leads to a significant shift of the NMR chemical shift, allowing quantification of the enantiomeric ratio. The new CSR has the advantages of a wide scope of analytes including ethers, haloalkanes, and alkanes, easy tunability of the degree of chemical shifts by measurement temperature, and erasability of proton signals of CSR because of the short spin-spin (T2) relaxation of the macromolecular scaffold.

A Traceless Chiral Shift Reagent Based on Nonbonding Interactions with Single‐Handed Helical Poly(quinoxaline‐2,3‐diyl)

AbstractA single‐handed poly(quinoxaline‐2,3‐diyl) (PQX) has been found to serve as a new type of chiral shift reagent (CSR) for determining the enantiomeric ratio by NMR spectroscopy. Even though there is no specific binding site in the PQX, its nonbonding interaction with chiral analytes leads to a significant shift of the NMR chemical shift, allowing quantification of the enantiomeric ratio. The new type of CSR has the advantages of a wide scope of analytes including ethers, haloalkanes, and alkanes, easy tunability of the degree of chemical shifts by measurement temperature, and erasability of proton signals of CSR because of the short spin‐spin (T2) relaxation of the macromolecular scaffold.

Praseodymium Metallacrown-Based NMR Probe for Enantioselective Discrimination of Mandelate Anions in Water.

Recently, the enhanced interest in water-soluble aminohydroximate Ln(III)-Cu(II) metallacrowns (MC) is largely due to their fascinating structural chemistry, diverse properties and ease of synthesis. We examined the water-soluble praseodymium(III) alaninehydroximate complex Pr(H2O)4[15-MCCu(II)Alaha-5]·3Cl (1) as a highly effective chiral lanthanide shift reagent for NMR analysis of the biologically relevant (R/S)-mandelate (MA) anions in aqueous media. The R-MA and S-MA enantiomers can be easily discriminated in the presence of small (1.2-6.2 mol %) amounts of MC 1 by the 1H NMR signals of multiple protons exhibiting an enantiomeric shift difference (ΔΔδ) of 0.06 ppm up to 0.31 ppm. Additionally, a possibility of coordination of MA to the metallacrown was investigated by the ESI-MS technique and a Density Functional Theory modeling of the molecular electrostatic potential and noncovalent interactions.

Efficient Preparation of Chloroquine Enantiomers via Crystallization Resolution and Palladium-Catalysed Coupling

Abstract: Chloroquine (CQ) was found to exhibit antiviral activity against novel coronaviruses, which makes the preparation of CQ enantiomers particularly important. In this work, we developed an efficient method for the preparation of CQ enantiomers by crystallization resolution and palladium-catalyzed coupling. The obtained chiral CQ had been fully assigned by 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC spectra. Moreover, the enantiomeric excess value of CQ was rapidly detected by binaphthol phosphate as a chiral NMR shift reagent.

Characterization of Capecitabine Loaded Stealth Liposomes by Nuclear Magnetic Resonance

Background Liposomes are lipid aggregates with a careful choice of lipid composition and process parameters. Liposomes are formulated by optimization of process parameters of liposomes to achieve desired bioavailability and to improve stability. Objectives The main objective of the present research was to formulate colon targeting capecitabine loaded stealth liposomes characterized by using Nuclear magnetic resonance NMR techniques to determine the fractions of the drug capecitabine CAP encapsulated in the liposomal suspension.Methods Liposome properties were evaluated by NMR. 31P-NMR 31Phosphorus NMR in combination with the use of chemical shift reagents were used for the identification of lamellarity of liposomes which can have a strong effect on both encapsulation efficiency and the efflux rate of encapsulated active compounds.Results The results suggested that capecitabine remained intact during the loading process and the liposomal drug was present in a soluble form. Conclusion 31P-NMR was found to be an effective method to study the lamellarity of liposomes and to determine the distributed fractions of encapsulated capecitabine.

C1-symmetric aza-crown ethers as chiral shift agents for amines and amino acid derivatives

Reported herein is our recent research progress in the development of macrocyclic chiral recognition studies. Highly enantiopure C1-symmetric aza-crown ethers, which were prepared previously by our lab from catalytic enantioselective symmetry-breaking C (sp3)-H bond transformation of readily available and inexpensive aza-crown ethers, were useful 1H NMR chiral shift reagents to resolve racemic amines and amino acid derivatives, providing an easy and rapid NMR assay of enantiomeric purity of chiral compounds, especially chromophore-devoid ones that are not detected and quantified by colorimetric method.

Inhibitory Effect of Lanthanides on Native Lipid Flip-Flop

The influence of ytterbium ions (Yb3+), a commonly used paramagnetic NMR chemical shift reagent, on the physical properties and flip-flop kinetics of dipalmitoylphosphatidylcholine (DPPC) planar supported lipid bilayers (PSLBs) was investigated. Langmuir isotherm studies revealed that Yb3+ interacts strongly with the phosphate headgroup of DPPC, evidenced by the increases in shear and compression moduli. Using sum-frequency vibrational spectroscopy, changes in the acyl chain ordering and phase transition temperature were also observed, consistent with Yb3+ interacting with the phosphate headgroup of DPPC. The changes in the physical properties of the membrane were also observed to be concentration dependent, with more pronounced modification observed at low (50 μM) Yb3+ concentrations compared to 6.5 mM Tb3+, suggesting a cross-linking mechanism between adjacent DPPC lipids. Additionally, the changes in membrane packing and phase transition temperatures in the presence of Tris buffer suggested that a putative Yb(Tris)3+ complex forms that coordinates to the PC headgroup. The kinetics of DPPC flip-flop in the gel and liquid crystalline (lc) phases were substantially inhibited in the presence of Yb3+, regardless of the Yb3+ concentration. Analysis of the flip-flop kinetics under the framework of transition state theory revealed that the free energy barrier to flip-flop in both the gel and lc phases was substantial increased over a pure DPPC membrane. In the gel phase, the trend in the free energy barrier appeared to follow the trend in the shear moduli, suggesting that the Yb3+-DPPC headgroup interaction was driving the increase in the activation free energy barrier. In the lc phase, activation free energies of DPPC flip-flop in the presence of 50 μM or 6.5 mM Yb3+ were found to mirror the free energies of TEMPO-DPPC flip-flop, leading to the conclusion that the strong interaction between Yb3+ and the PC headgroup was essentially manifested as a headgroup charge modification. These studies illustrate that the presence of the lanthanide Yb3+ results in significant modification to the lipid membrane physical properties and, more importantly, results in a pronounced inhibition of native lipid flip-flop.

Ion Mobility Shift Reagents for Lipid Double Bonds Based on Paternò-Büchi Photoderivatization with Halogenated Acetophenones.

The Paternò-Büchi (PB) reaction is a cycloaddition reaction between a carbon-carbon double bond (C═C) and a photochemically excited carbonyl-containing compound. The constrained ring formed between the C═C bond and the PB reagent is more susceptible to fragmentation by collision-induced dissociation, which facilitates identification of the C═C position within the fatty acyl tails of lipids. Although the original PB reaction using acetone had a low yield of derivatized lipids and therefore a low yield of diagnostic ions, a new generation of PB reagents based on halogenated acetophenones has improved the reaction yield substantially. In this study, we investigated the use of halogenated PB reagents and ion mobility to improve the identification of PB-derivatized lipids by shifting them out of the densely populated lipid region of ion mobility-mass spectrometry (IM-MS) space. Several halogenated PB reagents containing fluorine, chlorine and bromine were investigated for their ability to decrease the collision cross-section (CCS) values of derivatized lipids and yield sufficient intensity for both the derivatized lipid and its diagnostic ions. We found that 4'-chloro-2',6'-difluoroacetophenone (CDFAP) displayed the best performance, with an average decrease in CCS of 4.4% and yield of derivatized lipids and diagnostic ions comparable to the trifluorinated acetophenone reagent proposed by the Xia group. The unique isotope pattern resulting from the chlorine substituent aided in identification of the derivatized lipids and their diagnostic ions, as well. We further demonstrate that derivatization with CDFAP preserves the separation of lipids classes in IM-MS space.

23Na chemical shift imaging in the living rat brain using a chemical shift agent, Tm[DOTP]5–

ObjectiveIt is well known that the use of shift reagents (SRs) in nuclear magnetic resonance (NMR) studies is substantially limited by an intact blood–brain barrier (BBB). The current study aims to develop a method enabling chemical shift imaging in the living rat brain under physiological conditions using an SR, Tm[DOTP]5−.Materials and methodsHyperosmotic mannitol bolus injection followed by 60 min infusion of a Tm[DOTP]5− containing solution was administered via a catheter inserted into an internal carotid artery. We monitored the homeostasis of physiological parameters, and we measured the thulium content in brain tissue post mortem using total reflection fluorescence spectroscopy (T-XRF). The alterations of the 23Na resonance spectrum were followed in a 9.4T small animal scanner.ResultsBased on the T-XRF measurements, the thulium concentration was estimated at 2.3 ± 1.8 mM in the brain interstitial space. Spectroscopic imaging showed a split of the 23Na resonance peak which became visible 20 min after starting the infusion. Chemical shift imaging revealed a significant decrease of the initial intensity level to 0.915 ± 0.058 at the end of infusion.ConclusionOur novel protocol showed bulk accumulation of Tm[DOTP]5− thus enabling separation of the extra-/intracellular 23Na signal components in the living rat brain while maintaining physiological homeostasis.

An integrated strategy for chemical, biological and palynological standardization of bee propolis

An integrated method for standardization of propolis using chromatographic, spectroscopic, palynological and biological analyses was implemented in this study. Digitally-enhanced HPTLC images using dual visualization approach with four image analysis software packages adopting different digitalization algorithms were comparatively evaluated i.e.; Sorbfil TLC View®, ImageJ®, JustTLC® and Gel Analyzer®. ImageJ® and Gel Analyzer® showed superior figures of merits in case of flavonoids and phenolic acids quantitation, respectively. Unsupervised and supervised multivariable pattern recognition models were constructed for comprehensive discrimination between the three propolis types (blue, orange and green) collected from various geographical locations worldwide. HPTLC-ESI-MS was utilized for precise identification of the discriminatory phytoconstituents. Fingerprint-efficacy relationship analysis was conducted via an Orthogonal Projection to Latent Structure multivariate model to unravel the bio-efficient markers in terms of α-glucosidase and α-amylase inhibition as main targets. 3,4-Dimethoxycinnamic acid, caffeic acid, isoferulic acid, rosmarinic acid, and quercetin were found to be the main health-relevant markers. A complementary fast, simple and readily available UV spectroscopic method using aluminium chloride as bathochromic shift reagent was used as an independent method for prediction of aforementioned biomarkers using a validated Partial Least Squares Regression model. In addition, palynological analysis was implemented to determine the botanical origin of Egyptian propolis for the first time. Twenty-eight pollen types assigned to 13 families were identified, with Asteraceae being the highest representative one. The investigated samples lacked dominant pollen types, which reflected the multifloral origin of Egyptian propolis. Identification of plant sources of propolis, which directly affect its chemical composition and subsequently its biological efficacy represents an integral part of its standardization.

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

Ion mobility spectrometry (IMS) detects illegal substances and explosives in airports, ports, and customs. This is complicated by false positives caused by overlapping peaks. Shift reagents selectively change ion mobilities through adduction with analyte ions. This discriminates false positives because interferents and illegal substances respond differently to shift reagents. We introduced five different shift reagents using electrospray ionization-IMS-mass spectrometry to study the effect of interaction energy, intermolecular bonds, and analyte size on ion mobility shifts. Analyte ion-shift reagent interactions were calculated using Gaussian. The mobility shifts showed a decreasing trend as the molecular weight increased for a series of ten compounds. The shift in drift time better reflected the pure effect of shift reagents. Valinol was an exception to this trend because it had a low binding energy interaction with all shift reagents and, consequently, its clusters were short-lived. This produced fewer collisions against the buffer gas and a shorter drift time, compared to ions of similar molecular weight. The results of this investigation are important for understanding the behavior of shift reagents in resolving overlapping peaks that cause interferences. The suppression of false positives eases the transit of passengers and cargos, increases the confiscation of illicit substances, and saves money and distress due to needless delays in customs and airports.