Ion Trap Research Articles

Piezoresistive-piezocapacitive hybrid pressure sensor based on synergetic MXene porous conducting and ion trapping effects for operando battery state-of-charge monitoring

Battery pressure evolution provides essential information for battery state diagnosis. However, challenges still exist for achieving suitable pressure sensors to realize precise operando battery pressure monitoring. Herein, we develop a flexible hybrid pressure sensor by sandwiching one ionic piezocapacitive layer between two piezoresistive electrode networks. By taking advantage of the synergistic resistance and capacitance variation effects of the sensor upon compression by the interwoven conductive MXene fibers and the ionic nanofibers with MXene ion trappers, a remarkably improved sensing performance is achieved with a low detection limit of 4 Pa, an excellent durability under both small and ultrahigh pressures for over 20 000 cycles, and high sensitivities over an ultrawide detection range of 0–1 MPa. Meanwhile, the developed sensor is soft and stretchable, ensuring a convenient and conformal attachment to batteries of various shapes without in-plane strain interference. Towards practical application, the hybrid sensor is used to monitor the pressure evolution of lithium-ion battery pouch cells under different constrained pressures, and highly sensitive response is gained, through which the state of charge (SoC) of the battery during normal operation can be precisely estimated. When the battery is slightly overcharged, an instant warning can be made upon the diagnosis of SoC of even a few percentages over 100 %. Its application can be expanded to other areas where high sensitivity across an ultrawide detection range is demanded.

A trapped ion mobility enabled Fourier transform ion cyclotron resonance mass spectrometer for infrared ion spectroscopy at FELIX

We report the installation of a new infrared ion spectroscopy platform at the free-electron laser facility FELIX, based on a Bruker SolariX Fourier Transform ion cyclotron resonance (FT-ICR) mass spectrometer equipped with a trapped ion mobility spectrometry (TIMS) stage. The instrument allows one to record infrared multiple-photon dissociation (IRMPD) spectra for mass and mobility selected ions, produced by a range of ion sources. We describe two strategies to achieve consistent overlap between the laser beam and the ion packet. Removing the original ECD cathode significantly enhanced the IR transmission and the overlap with the ion cloud, resulting in improved IRMPD yield per pulse. Enhancement of the photodissociation yield is observed when multiple pulses are used, as there is negligible collisional deactivation in the ultra-high vacuum trapping region of the ICR cell. We compare IRMPD spectra recorded on the new platform with IRMPD spectra of the same species recorded on one of our 3D-quadrupole ion trap platforms. We demonstrate the instrument’s performance using a sample containing a mixture of two trisaccharides. Mobility selection allows us to record individual IR spectra for the two isomeric species. This multi-modal platform, encompassing liquid chromatography, ion mobility spectrometry, ultra-high resolution (tandem) mass spectrometry, infrared ion spectroscopy (and soon also mass spectrometry imaging), is available to users at the FELIX facility.

Cryogenic Ion Vibrational Spectroscopy of Protonated Valine: Messenger Tag Effects.

We report the infrared photodissociation spectrum of tagged protonated valine in the range 1000-1900 cm-1, prepared in a cryogenic ion trap. Comparison of experimental results with calculated infrared spectra based on density functional theory shows that the hydroxyl group of the carboxylic acid functionality and the protonated amine group adopt a trans configuration. Nitrogen and methane molecules were used as messenger tags with optimal tagging temperatures of 30 K for N2 and 60 K for CH4. While the calculated infrared spectra of the tagged ion suggest only a weak influence of the messenger tag on the frequency positions of ValH+, the measured intensities for N2-tagged ValH+ appear strongly suppressed for all but the highest frequency feature at 1773 cm-1. We trace this behavior to the binding energy of the N2 tag, which is significantly higher than that of CH4, based on density functional and coupled cluster calculations and rate estimates for photoinduced unimolecular dissociation from statistical theory.

Realization of Higher Resolution Charge Detection Mass Spectrometry.

Charge detection mass spectrometry (CD-MS) allows mass distributions to be measured for heterogeneous samples that cannot be analyzed by conventional MS. With CD-MS, the m/z and charge are measured for individual ions using a detection cylinder embedded in an electrostatic linear ion trap (ELIT). Imprecision in both the m/z and charge measurements contribute to the mass resolution. However, if the charge can be measured with a precision of <0.2 e the charge state can be assigned with a low error rate and the mass resolving power only depends on the m/z resolution. Prior to this work, the best resolving power demonstrated experimentally for CD-MS was 700. Here we demonstrate a resolving power of >14,600, 20-times higher than the previous best. Trajectory simulations were used to optimize the geometry and electrostatic potentials of the ELIT. We found conditions where the energy dependence of the oscillation frequency becomes parabolic, and then operated with a nominal ion energy at the minimum of the parabola. The 14,600 resolving power was obtained with a beam collimator before the ELIT. With the collimator removed, the resolving power of the optimized ELIT is 7300, which is still an order of magnitude higher than the previous best. The resolving power was demonstrated by resolving the isotope distributions for peptides and proteins. High resolution CD-MS measurements were then used to resolve the glycans on a monoclonal antibody and applied to the analysis of hepatitis B virus capsids. The results indicate that procedures for adduct removal need to be improved for the full benefit of the higher resolving power to be realized for higher mass species. However, these results represent a key step toward using CD-MS to analyze very complex protein mixtures where charge states are not well resolved in the m/z spectrum because of congestion from numerous overlapping peaks.

The linear Paul Trap's Confined Stability Area for 40Ca+ Ions

تقدم تكنولوجيا الكم طرقًا حسابية واتصالات ومحاكاة وقياسًا جديدة. تحتاج أجهزة الكمبيوتر التقليدية إلى المساعدة في حل المشكلات المهمة مثل التحليل بسبب الزيادات الهائلة في وقت الحساب. ومع ذلك، تستخدم أجهزة الكمبيوتر الكمومية ميكانيكا الكم لحجم المشكلة الأسي الفرعي ويمكنها محاكاة الطبيعة على المستوى الكمي. يهتم العلماء بشكل متزايد بتطوير أجهزة الكمبيوتر الكمومية باستخدام ذرات متأينة مفردة في مصائد باولي. تمثل الحالة الأساسية لكل أيون أقل قيمة ممكنة للبت الكمي. تم استخدام الأيونات المحتجزة 40Ca+ في إحدى الدراسات كمثال على الكيوبت الكمومي. تم استخدام برنامج MATLAB على العوامل النموذجية التي تؤثر على الحالة المقيدة وتأثيراتها. يجب أن تكون الحلول مستقرة في كلا الاتجاهين، مما يتطلب حصرًا ثلاثي الأبعاد لمعادلة ماثيو. تؤثر المتغيرات على المسافة من مركز المصيدة لنهاية القطب، وجهد UDC، وكتلة الأيون، والترددات الراديوية. تم استخدام جهد متغير للتحكم وإظهار تأثيره على سلسلة محددة من الأيونات المحاصرة. يهدف هذا البحث إلى فهم أفضل للظروف المثلى للحجز وحركة الأيونات من الحالة (4S1/2) إلى الحالة (4P1/2) بالرنين. تخضع الحالة الكمومية للتعديل والتغيير، مما يجعلها أداة واعدة لحل المشكلات المعقدة.

Disposition Kinetics of Cathinone and its Metabolites after Oral Administration in Rats.

Cathinone is a natural stimulant found in the Catha edulis plant. Its derivatives make up the largest group of new psychoactive substances. In order to better understand its effects, it is imperative to investigate its distribution, pharmacokinetics, and metabolic profile. However, the existing literature on cathinone remains limited. This study aimed to investigate the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathinone and cathine concentrations were identified and quantified using ion trap liquid chromatography- mass spectrometry (LC-IT/MS). The metabolic profile in the serum, brain, lung, liver, kidney, and heart was analyzed at specific time points (0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours) using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method. The highest concentration of cathinone was found in the kidney (1438.6 μg/L, which gradually decreased to 1.97 within 48 h and disappeared after 72 h. Cathinone levels in the lungs, liver, and heart were 859, 798.9, and 385.8 μg/L, respectively, within half an hour. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 μg/L and became undetectable after 24 h. In the rat brain, cathinone levels dropped quickly and were undetectable within six hours, decreasing from 712.7 μg/L after 30 min. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours, indicating slower conversion of cathinone to cathine in the brain and serum. This study revealed a dynamic interplay between cathinone disposition kinetics and its impact on organ-specific metabolic profiles in rats. These results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. Investigating the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine is essential for informed decision- making in medical practices and further research into the pharmacological properties of cathinone.

Determination of product ions emerged from dications by varying retarding electric field in reflectron time-of-flight mass spectrometer supported by ion trajectory simulations

Investigation of the metastable dissociations clarifies the characteristics of ionic states. Tandem mass spectrometry using an ion trap mass spectrometer, a time-of-flight mass spectrometer (TOF-MS), and the combination of those spectrometers were used for the analysis of metastable dissociation. However, investigation of the metastable dissociations of multiply charged ions is not straightforward because collision-induced charge transfer reactions to lose charges should be avoided. TOF-MS equipped with a reflectron (refTOF-MS) maintained under high vacuum condition is one of the suitable instruments. However, another difficulty arises due to the working principle of refTOF-MS: The product ions whose m/z is greater than that of multiply charged precursor ions can pass through a reflectron under the experimental conditions for detecting the product ions of a singly charged precursor ion. In this study, we report the ionization of decafluorobiphenyl (DFB) by femtosecond laser pulses and the determination of the product ions emerged from doubly charged precursor ions using a refTOF-MS. Detection of ions behind a reflectron by varying the retarding potential of a reflectron enables us to identify the m/z of product ions in two ways: measurement of the threshold retarding potential reflecting product ion; comparing the relative flight time of the product ions obtained by experiments and ion trajectory simulations. We have reported three and one metastable dissociation channels of DFB+ and DFB2+, respectively, by a conventional product ion analysis, that is the selection of a precursor ion and its product ions using an ion gate followed by the reflection and separation of them by a reflectron. In this study, we further identified the products that passed through a reflectron: charge transfer product of C2+; the product ion of C4F22+ which is a secondary product of DFB ion; the product ion of DFB2+. The detection of the product ions that passed through a reflectron expanded the measurable m/z range of product ions emerged from doubly charged precursor ions.

Mass-selective instability and resonance ejection modes for DIT with rectangular asymmetric wave shape.

We consider the operation of a digital linear ion trap with resonance radial ejection and mass selective instability modes. Periodic wave shape has a positive part with amplitude and duration and negative part with amplitude and duration , where T is the period. The mapping of the stability diagram, calculations of the well's depth and ion oscillations spectra are presented. The process of resonant excitation of ion oscillations by a dipole sinusoidal signal is studied, as well as ion ejection at the stability boundary. The trajectory method is used for this purpose. It is shown that the mass selectivity of dipole excitation is twice as large for rectangular wave shape compared to sinusoidal wave shape. Increasing the diameter of the round rods of the linear trap gives an increase in the resolving power. The possibility of DIT operation in mass-selective instability mode at the boundary point is discussed.

Multi-omics reveals bufadienolide Q-markers of Bufonis Venenum based on antitumor activity and cardiovascular toxicity in zebrafish

BackgroundBufonis Venenum (BV) is a traditional animal-based Chinese medicine with therapeutic effects against cancer. However, its clinical use is significantly restricted due to associated cardiovascular risks. BV's value in China's market is typically assessed based on “content priority,” focusing on indicator components. However, these components of BV possess both antitumor activity and toxicity, and the correlation between the antitumor activity and toxicity of BV has not yet been elucidated. PurposeThis study employs an integrated multi-omics approach to identify bufadienolide Q-markers and explore the correlation between BV's antitumor activity and toxicity. The aim is to establish a more comprehensive method for BV's quality. MethodsNormal zebrafish and HepG2 xenograft zebrafish were chosen as activity and toxicity evaluation models. Ultra-high performance liquid chromatography (UHPLC) coupled with a linear ion trap orbitrap (LTQ-Orbitrap) mass spectrometry was used to quantify eight batches of BV and key “toxic and effective” components were screened out. Transcriptomic and metabolomic analyses were performed to elucidate the regulatory mechanisms underlying the antitumor activity and cardiovascular toxicity of the key components in BV. ResultsEight key “toxic and effective” compounds were identified: resibufogenin, cinobufagin, arenobufagin, bufotalin, bufalin, gamabufotalin, desacetylcinobufagin, and telocinobufagin. The findings showed that bufalin and cinobufagin interfered with calcium homeostasis through CaV and CaSR, induced cardiotoxicity, and upregulated CASP9 to activate myocardial cell apoptosis. However, desacetylcinobufagin exhibited greater potential in terms of anti-tumor effects. Combining the results of untargeted and targeted metabolomics revealed that desacetylcinobufagin could have a callback effect on differential lipids and correct abnormal energy and amino acid metabolism caused by cancer, similar to cinobufagin and bufalin. Microscale thermophoresis (MST) ligand binding measurements also showed that the binding of desacetylcinobufagin to GPX4 has a more potent ability to induce ferroptosis in tumor cells compared to cinobufagin. ConclusionAn innovative evaluation method based on the zebrafish was developed to investigate the relationship between the toxicity and efficacy of BV. This study identified toxicity and activity Q-markers and explored the mechanism between the two effects of BV. The research data could offer valuable insights into the efficacy of BV. Additionally, desacetylcinobufagin, an active ingredient with low toxicity, was found to enhance the quality of BV.

Realization of a chip-based hybrid trapping setup for 87Rb atoms and Yb+ ion crystals.

Hybrid quantum systems integrate laser-cooled trapped ions and ultracold quantum gases within a single experimental configuration, offering vast potential for applications in quantum chemistry, polaron physics, quantum information processing, and quantum simulations. In this study, we introduce the development and experimental validation of an ion trap chip that incorporates a flat atomic chip trap directly beneath it. This innovative design addresses specific challenges associated with hybrid atom-ion traps by providing precisely aligned and stable components, facilitating independent adjustments of the depth of the atomic trapping potential, and positioning trapped ions. Our findings include the simultaneous loading of the ion trap with linear Yb+ ion crystals and the loading of neutral 87Rb atoms into a mirror magneto-optical trap.

Laboratory Benchmark of n ≥ 4 Dielectronic Recombination Satellites of Fe xvii

We calculated cross sections for the dielectronic recombination (DR) satellite lines of Fe xvii and benchmarked our predictions with experimental cross sections of Fe xvii resonances that were monoenergetically excited in an electron-beam ion trap. We extend the benchmark to all resolved DR and direct electron-impact excitation (DE) channels in the experimental data set, specifically the n ≥ 4 DR resonances of Fe xvii, complementing earlier investigations of n = 3 channels. Our predictions for the DR and DE absolute cross sections for the higher n complexes disagree considerably with experimental results when using the same methods as in previous works. However, we achieve agreement within ∼10% of the experimental results by an approach whereby we doubly convolve the predicted cross sections with both the spread of the electron-beam energy and the photon energy resolution of our experiment. We then calculated rate coefficients from the experimental and theoretical cross sections, finding general agreement within 2σ with the rates found in the OPEN-ADAS atomic database.

Diffraction order penalization to improve spectrometer calibrations

Wavelength calibration in diffraction spectroscopy typically depends on identifying strong, well-known lines in the recorded spectra and fitting a calibration function to them. In this paper, we outline a novel method (order penalization) for improving spectroscopic calibrations by extending non-linear least squares fitting of the calibration curve. The method introduces an extra term into the minimized quantity that penalizes disagreement in the positions of spectral lines observed in multiple diffraction orders. The primary advantage of this method is that the lines used do not have to be identified, except for establishing the fact that they are different orders of the same line. This increases the number of constraints on the calibration curve, potentially in spectral regions where no regular calibration lines are available. The mathematical basis of this method is described, and the performance of this method is evaluated on simulated data and experimental data from the National Institute of Standards and Technology (NIST) Electron Beam Ion Trap. We demonstrate the effectiveness of the method on the spectra of highly charged Ag-like Re28+ and nearby charge state ions.

A compact ion source combining electron-impact and thermal ionization for multiple-reflection time-of-flight mass spectrometry.

A compact ion source combining electron impact and thermal ionization has been developed and commissioned in two Multiple-Reflection Time-Of-Flight Mass Spectrometer (MR-TOF-MS) setups at the Fragment Separator Ion Catcher at the GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany, and at TRIUMF's Ion Trap for Atomic and Nuclear science at TRIUMF Canada's particle accelerator center, Vancouver, Canada. The ion source is notable for its compact dimensions of 50mm in height and 68mm in diameter. The ion source is currently in daily operation at both facilities. Design, simulations, and results of combining ions from thermal and electron-impact ionization of different gases (perfluoropropane and sulfur hexafluoride) are presented in this work. The systematic effects of heating power on the thermal source were studied in detail. The source has demonstrated stable and long-term production of reference ions over a wide mass range for the MR-TOF-MS. This versatile ion source has also been used to optimize and investigate the transport of ions with different chemical reactivity and ionization potentials.

Development of an atomic spectra research platform based on a 30-keV electron beam ion trap.

Electron Beam Ion Traps (EBITs) serve as efficient tools for producing and studying highly charged ions. In response to the diagnostic requirements of upcoming magnetic confinement fusion devices, a medium-energy atomic spectra research platform based on a compact EBIT is developed. This platform achieves a central magnetic field of up to 1.0T, with electron beam currents reaching 20 mA and electron energies up to 30keV, similar to the electron temperature on fusion reactors. The developed atomic spectra platform successfully provided spectral data for elements such as argon, xenon, iron, and tungsten. This platform stands as a valuable asset for advancing research in nuclear fusion, particularly concerning impurity spectroscopic diagnostics.

Neurotransmitter metabolites in milk ferments of Leuconostoc mesenteroides regulate temperature-sensitive heartbeats in an ex ovo model

Accumulated evidence has supported the probiotic activity of Leuconostoc mesenteroides (L. mesenteroides) which can yield beneficial metabolites via fermentation. Here, bovine milk rich in phenylalanine（PHE) was used as a source for fermentation of L. mesenteroides. The complexes of PHE with bacterial phenylalanine hydroxylase (PheH) at two temperatures were revealed via molecular dynamics simulation. Two carbon hydrogen bonds and a Pi-Alkyl T-shaped interaction were newly formed at an active site of the PheH-PHE complex. The PheH interacted with two different hydrogen atoms in an amine of PHE via conventional hydrogen bonds at 37 °C, a temperature that accelerated the milk fermentation of L. mesenteroides. Twenty-eight metabolites including various neurotransmitters in fermented milk were identified and quantified by liquid chromatography coupled to quadrupole ion trap (Q-Trap) tandem mass spectrometry. Ex ovo injection of milk ferments into the yolk sac of chicken embryos enhanced a rising temperature-induced increase in heartbeats towards the normal resting level. The neurotransmitter-rich milk ferments hold potential for using to adjust energy metabolism, referred from heart rates, during fluctuating temperature conditions.

Tracking the extensive three-dimensional motion of single ions by an engineered point-spread function

Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.

Fourier Transform Ion Trap Mass Analysis by Deciphering Ion Ejection Signals in the Frequency Domain.

Mass analysis in an ion trap is conventionally realized through time domain analysis of the ejected ion current collected from an electron multiplier (EM), in which the ion ejection time is found to have a correlation with the mass-to-charge (m/z) ratio of the ion. In this study, we investigated a new method for mass analysis by examining ion ejection signals in the frequency domain. Theoretical analysis and ion trajectory simulations show that ions of the same m/z ratio are ejected from an ion trap at regular intervals, producing a periodic pulsed signal on the EM. The period of this pulsed ejection signal is directly linked to the m/z values of the ions. To realize this method experimentally, a broadband preamplifier was built and integrated on a miniature ion trap mass spectrometer (the "Brick" series from Nier Inc.) to capture this pulsed ion ejection signal collected from the EM. Experimental results were in good agreement with theoretical and simulation analyses. This method has the potential to improve the mass resolution of an ion trap mass analyzer. As a proof-of-concept demonstration, a peak width of 0.1 Da at a m/z value of 281 was achieved in experiments.

Gas-Phase Characterization of Redox-Active Manganese Complexes.

Manganese complexes exhibit a rich redox chemistry, usually accompanied by structural reorganization during the redox processes often followed by ligand dissociation or association. The push-pull ligand 2,6-diguanidylpyridine (dgpy) stabilizes manganese in the oxidation states +II, +III, and + IV in the complexes [Mn(dgpy)2]n+ (n = 2-4) without change in the coordination sphere in the condensed phase [Heinze et al., Inorganic Chemistry, 2022, 61, 14616]. In the condensed phase, the manganese(IV) complex is a very strong oxidant. In the present work, we investigate the stability and redox activity of the MnIV complex and its counterion (PF6-) adducts in the gas phase, using two modified 3D Paul ion trap mass spectrometers. Six different cationic species of the type [Mnx(dgpy)2(PF6)y]n+ (x = II, III, IV, y = 0-3, n = 1-3) could be observed for the three oxidation states MnIV, MnIII, and MnII, of which one observed complex also contains a reduced dgpy ligand. MnII species showed the highest relative stability in collision induced dissociation and UV/vis photo dissociation experiments. The lowest stability is observed in the presence of one or more counterions, which correlates to a lower total charge n+. Gas phase UV/vis spectra show similar features as the condensed phase spectra only differing in relative band intensities. The strongly oxidizing MnIV complex reacts with triethylamine (NEt3) in the gas phase to give MnIII, while MnIII species show little reactivity toward NEt3.

Microchip Liquid-Phase Ion Trap for Online Mass Spectrometry Analysis.

Liquid-phase ion trapping (LPIT) was proposed recently for ion manipulations in liquid channels. When coupled with mass spectrometry, LPIT exhibits considerable potential in applications such as target enrichment and bottom-up proteomics. However, further evolution of LPIT techniques requires flexible field designs including electric and fluid fields. In this study, LPIT was constructed and implemented on microfluidic chips. Utilizing conductive polymers, nonlinear potential distribution was achieved in the liquid channel, enabling the focusing of ions at distinct locations based on their effective charges and hydrodynamic radii. The integration of an electrospray ionization source facilitated coupling of the LPIT chip with a mass spectrometer. The working mechanism and parameter optimizations were explored through a combination of theoretical analysis and numerical simulations. Experiments showcased the LIPT chip's proficiency in enrichment and separation capabilities. The detection sensitivity of the following mass spectrometer could be improved by ∼10-fold. A good linearity (R2 > 0.99) was obtained for reserpine in the range of 1-100 ng/mL. The separation capability was demonstrated using a mixture of 11 amino acids.

Metabolic characteristic profiling of 1-amino-3,3-dimethyl-1-oxobutan-2-yl-derived indole and indazole synthetic cannabinoids in vitro

Characterizing the metabolic profiles of synthetic cannabinoids (SCs), a type of new psychoactive substances, is of particular importance for forensic detection and analysis. Although the metabolism of individual SCs derived from 1-amino-3,3-dimethyl-1-oxobutan-2-yl (ADB-SCs) has been reported, their metabolites also undergo a continuous change and combination of their tail and core regions. Therefore, elucidating the metabolic characteristics and effects of these structures is essential to enhance our understanding. In this study, the human liver microsome was used as the model for studying the in vitro phase I metabolism of 12 ADB-SCs, and the metabolites obtained were analyzed using ultra-high performance liquid chromatography–tandem four-level rod-electrostatic field orbital ion trap mass spectrometry to determine type, structure, and relative contents. The results indicated that hydroxylation and N-dealkylation were the major metabolic pathways in 12 ADB-SCs. The effects of the core and tail on the metabolism of these ADB-SCs were studied using theoretical calculations. For N-dealkylation metabolism, the strong electron-withdrawing conjugative effect of the –N= moiety in the pyrazole ring, steric hindrance of the tail, and electronic effect of substituents on the tail significantly affected metabolism. Further, it changed the relative contents of N-dealkylation metabolites. For hydroxylation, the reaction types were inconsistent at different parts. For instance, the phenyl group of the core is electrophilic, and its electron cloud density determines whether the phenyl group can be hydroxylated at the specific metabolic sites. Meanwhile, hydroxylation of the neopentyl moiety of the linked group involves the oxidation of aliphatic C–H bonds, whereas amide–hydroxylamine tautomerism affects hydroxylation metabolism. When the alkyl chain in the tail contains functional groups (such as –F and >CC<), oxidative defluorination or dihydrodiol metabolites are produced. Taken together, we systematically determined d the effect of functional groups in the core and tail of ADB-SCs on their metabolism, validating confirmed the feasibility of ADB-SC metabolism prediction based on their structural characteristics.