Ion-pair Research Articles

Fragmentation and Isomerization Pathways of Natural and Synthetic Cannabinoids Studied via Higher Collisional Energy Dissociation Profiles

Cannabinoid molecules are the family of molecules that bind to the cannabinoid receptors (CB1 and CB2) of the human body and cause changes in numerous biological functions including motor coordination, emotion, and pain reception. Cannabinoids occur either naturally in the Cannabis Sativa plant or can be produced synthetically in the laboratory. The need for accurate analytical methods for analyzing cannabinoid molecules is of considerable current importance due to demands for detecting illegal cannabinoids and for monitoring the manufacture of popular, non-illegal cannabinoid products. Mass spectrometry has been shown to be an optimum technique for identifying cannabinoids. In this work, we perform Higher Collisional Dissociation (HCD) mass spectrometric measurements on an Orbitrap Fusion Tribrid Mass Spectrometer to measure the collision-energy-dependent molecular fragmentation pathways of a group of key cannabinoids and their metabolites (cannabidiol, Δ9-Tetrahydrocannabinol, 11-Hydroxy-Δ9-tetrahydrocannabinol, 11-nor-9-Carboxy-Δ9-tetrahydrocannabinol, cannabidiolic acid, tetrahydrocannabinolic acid), along with two synthetic cannabinoids (JWH-018 and MDMB-FUBINACA). This is the first time that cannabinoid molecules have been studied using energy-resolved HCD methods. We identified a number of common, primary fragmentation pathways, including loss of water, loss of other small neutral molecule units (e.g., butene), and rupture of the central C-C bond that links the aromatic and alkyl ring groups. Quantum chemical calculations are presented to provide insights into preferred protonation sites and to characterize isomerization of protonated open-ring cannabinoids (e.g., [CBDA + H]+) into closed-ring analogues (e.g., [THCA + H]+). A key result to emerge from our study is that energy-resolved HCD measurements are particularly valuable in identifying isomerization, since the isobaric pairs of molecular ions studied here (e.g., [CBDA + H]+ and [THCA + H]+) are associated with identical HCD profiles indicating that isomerization of one structure into the other has occurred during the electrospray–mass spectrometry process. This is an important result as it will have general applicability to other tautomeric ions and thus demonstrates the application of energy-resolved HCD as a tool for identifying tautomerization proclivity.

Tailored Supramolecular Additives to Control the Crystallization Process and Morphology of MAPbI3.

Perovskite films feature unique optoelectronic properties, rendering them promising for electronic devices. The properties depend on the morphology on a broad range of length scales from nanometers to millimeters, influenced by a variety of factors. However, controlling the morphology is challenging. A tailored supramolecular additive, N, N'-bis(2-aminoethyl) terephthalamide is developed to control the intermediate and perovskite crystallization of methyl ammonium lead iodide (MAPbI3) and enhance the thermal and moisture stability in the final film. Reversible coordinative interactions of the carbonyl groups with Pb2+ ions via Lewis acid-base adduct and subsequent ion-ion interactions of the peripheral ammonium groups with the perovskite grain boundaries are combined which is stabilized by a strong hydrogen bonding pattern formed between the amide moieties of the additive molecules. Adding low amounts of this additive to the precursor solution significantly decelerates the structure formation and systematically reduces the crystallite size. Slower growth of the intermediate phases and the incorporation of the additive to the grain boundary is observed with multiple time-resolved techniques. Evidence for the formation of single-molecule interlayers between the MAPbI3 crystals and the presence of directed supramolecular interaction between additive molecules is shown. Transferability of this approach to other perovskites is anticipated, paving the way to improved processing control and stability.

Quantum Mechanics-Calibrated Classical Simulation of Earth-Abundant Divalent Metal Bis(trifluoromethanesulfonyl)imide Molar Conductivity in Organic Cosolvents with Onsager Transport Formalism.

Molar conductivities are one of the fundamental transport properties of electrolytes that reflect the complex and dynamic interactions between ions and solvents comprehensively. The quantitative accuracy of experimental input-free simulations of molar conductivities is strongly influenced by the underlying interaction parameters employed in the model. When validated with experimental molar conductivities, the developed model could be used to reveal further atomistic level details about the solvation structures and correlated ion pair formation, providing in-depth knowledge about solution physical chemistry and shedding light on electrolyte-solvent system design rules. Divalent cations are more challenging to model than monovalent cations due to their higher charge densities and stronger interactions with the environment. Yet, they started attracting significant attention for next-generation energy storage purposes. In this work, we focus on two earth-abundant divalent cation electrolytes, Mg(TFSI)2 and Ca(TFSI)2 in a dimethylacetamide-tetrahydrofuran (DMA-THF) cosolvent system. We used quantum mechanical cluster models to optimize the force field parameters (including the pairwise nonbonded interaction parameters and atomic charges) to be applied in classical simulations. With the reliable force field model, we discussed the importance of including ion correlation explicitly in predicting the molar conductivities via the Onsager formalism and showed that the conventional Nernst-Einstein formula overestimates ionic mobilities due to its intrinsic independent and uncorrelated particle assumption. Further, we investigated the solvation structures and ion pair formations. We concluded that the suitability of the interaction potentials utilized in a classical model for particular systems needs to be assessed not solely by directly comparing the simulated molar conductivities with the measured ones but, more importantly, by using the correct formalism (Onsager) to deduce the simulated result from dynamics trajectories.

Development of a Highly Selective Synthesis of 4–Substituted Tetrahydroquinolines: Substrate Scope and Mechanistic Study

Herein, we describe a general and selective deprotonation functionalization reaction of tetrahydroquinolines at the 4–position using organolithiums and phosphoramide ligands. In addition to the development of a direct deprotonation alkylation reaction with primary and secondary alkyl halides, a Negishi cross–coupling protocol was realized to afford products with a range of aromatic halides. These methods were applied to the late‐stage installation of tetrahydroquinolines into a variety of substrates including pharmaceuticals as well as natural product analogues. The use of thorough mechanistic investigations revealed the aggregation state of the newly formed tetrahydroquinoline anion to be a separated ion pair, which proved critical to optimizing the reaction conditions.

Precise Regulation of Intra-Nanopore Charge Microenvironment in Covalent Organic Frameworks for Efficient Monovalent Cation Transport.

Charged channels are considered an effective design for achieving efficient monovalent cation transport; however, it remains challenging to establish a direct relationship between charge microenvironments and ionic conductivity within the pores. Herein, we report a series of crystalline covalent organic frameworks (COFs) with identical skeletons but different charge microenvironments and explore their intra-pore charge-driven ion transport performance and mechanism differences. We found that the charged nature determines ion-pair action sites, modes, host-guest interaction, thereby influencing the dissociation efficiency of ion pairs, the hopping ability of cations, and the effective carrier concentration. The order of transport efficiency for Li+, Na+, and H+ follows anion > zwitterion > cation > neutrality. Ionic COFs exhibit up to 11-fold higher ionic conductivity than neutral COFs. Notably, the ionic conductivity of anionic COF achieves 2.0×10-4 S cm-1 for Li+ at 30°C and 3.8×10-2 S cm-1 for H+ at 160°C, surpassing most COF-based ionic conductors. This COF platform for efficient ion migration and stable battery cycling in lithium-metal quasi-solid-state batteries has also been verified as proof of concept. This work offers new insights into the development and structure-activity relationship studies of the next generation of solid-state ionic conductors.

Chemical Footprints of Thorium and Uranium in Molten LiF-BeF2 Explored by First-Principles Molecular Dynamics Simulations.

The chemical forms and transport properties of thorium and uranium ions in molten LiF-BeF2 are systemically studied via first-principles molecular dynamics simulations. The densities, diffusion coefficients, densities of electronic states, and ionic pair and cluster structures of molten LiF-BeF2-ThF4 (FLiBeTh), LiF-BeF2-UF4 (FLiBeU), and LiF-BeF2-ThF4-UF4 (FLiBeThU) are analyzed in detail. Studies have shown that the density and thermal expansion coefficient of molten FLiBeTh are higher than those of FLiBeU in the temperature range of 873-1073 K. Besides, FLiBeTh has higher electron energy, and the active Th electrons contribute to the diversification of its coordination structure and the improvement of diffusion property. Furthermore, the concept of Be-F tetrahedron stress index (SIT) is proposed in molten FLiBe, and the higher SIT of molten FLiBeU is one of the structural factors leading to slow diffusion coefficients of Be and F ions. Overall, the understanding and characterization of fuel salt structure and property are underscored, and the relationships between microstructure and diffusivity performance are preliminarily established.

Precise Regulation of Intra‐Nanopore Charge Microenvironment in Covalent Organic Frameworks for Efficient Monovalent Cation Transport

Charged channels are considered an effective design for achieving efficient monovalent cation transport; however, it remains challenging to establish a direct relationship between charge microenvironments and ionic conductivity within the pores. Herein, we report a series of crystalline covalent organic frameworks (COFs) with identical skeletons but different charge microenvironments and explore their intra‐pore charge‐driven ion transport performance and mechanism differences. We found that the charged nature determines ion‐pair action sites, modes, host‐guest interaction, thereby influencing the dissociation efficiency of ion pairs, the hopping ability of cations, and the effective carrier concentration. The order of transport efficiency for Li+, Na+, and H+ follows anion > zwitterion > cation > neutrality. Ionic COFs exhibit up to 11‐fold higher ionic conductivity than neutral COFs. Notably, the ionic conductivity of anionic COF achieves 2.0×10‐4 S cm‐1 for Li+ at 30°C and 3.8×10‐2 S cm‐1 for H+ at 160°C, surpassing most COF‐based ionic conductors. This COF platform for efficient ion migration and stable battery cycling in lithium‐metal quasi‐solid‐state batteries has also been verified as proof of concept. This work offers new insights into the development and structure‐activity relationship studies of the next generation of solid‐state ionic conductors.

Simultaneous determination of 51 indazole-type synthetic cannabinoids in urine and blood by online solid-phase extraction-liquid chromatography-linear ion trap mass spectrometry

To evade legal controls, new psychoactive substances (NPS), which have been designed as substitutes for traditional and synthetic drugs, are gradually dominating the drug market. Synthetic cannabinoids (SCs), which account for the majority of NPS, are rapidly being derivatized; consequently, controlling increasing abuse by merely listing individual compounds is difficult. Therefore, China has included the entire SC category of SCs listed as legal controlled substances since July 1, 2021. However, new SCs obtained through structural modification are still appearing and pose significant analytical challenges for forensic laboratories. Therefore, an efficient, green, and automated detection method is urgently required to provide technical support for the accurate screening actual samples. Meanwhile, the number of indazole-type SCs has increased sharply since 2013, which is ascribable to their stronger psychoactive effects. Indeed, forensic laboratories mainly analyze this key SC subclass. Therefore, in this study, we developed a new method for analyzing 51 indazole-type SCs in human urine and blood, which involves online solid-phase extraction (online SPE) as the preprocessing technology, with analysis performed using liquid chromatography-linear ion trap mass spectrometry. Deproteinization was achieved by adding acetonitrile, with dilution performed using 10 mmol/L ammonium acetate solution (pH 4.8) containing 0.1% formic acid. Samples were then analyzed directly using acetonitrile-10 mmol/L ammonium acetate aqueous solution (containing 0.1% formic acid) as the mobile phase. The mass-to-charge ratios of protonated molecular ions ([M+H]+) in the mass spectra acquired in full-scan mode, and the retention times in the chromatograms of the analytes were selected with the aim of monitoring the MS2 ions of the various compounds. Characteristic fragment ions of the various SC structures were summarized, with five groups of isomers, each containing ten compounds, successfully distinguished using multistage mass spectrometry and their retention times. Multistage MS was used to qualitatively screen 51 indazole-type SCs, which were then quantitatively analyzed using MS2 ion pairs (as quantitative ion pairs). The analytes exhibited limits of detection (LODs) of 0.02-1 ng/mL, with limits of quantification (LOQs) of 0.04-4 and 0.1-4 ng/mL in urine and blood, respectively. Linear fitting (weighting factor 1/x) revealed good linearity for each analyte within its respective linear range, with correlation coefficients (R2) greater than 0.99 in both urine and blood. The validity of the analytical method was tested by determining precision and spiked recovery values (n=6). Recoveries of 83.47%-116.95% were obtained at LOQ levels, with precisions of 2.29%-13.40%. In addition, recoveries of 86.63%-113.38% and precisions of 0.58%-13.79% were obtained at low, medium, and high levels. The method described herein is not only easy to operate but also can be automated. Indeed, high-throughput sample analysis was achieved when sample extraction, enrichment, and analysis were performed in dynamic mode through valve switching. Meanwhile, the method exhibited good sensitivity and is applicable to a wider range of compounds than those previously reported; it also provides a scientific basis and technical support for the rapid screening and quantitative analysis of SCs in actual relevant cases.

Determination of eldecalcitol in human plasma by SIL-IS UPLC-APCI-MS/MS method for pharmacokinetics study.

Eldecalcitol is a novel analog of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the treatment of patients with osteoporosis. A highly sensitive and specific ultra-performance liquid chromatography coupled to atmospheric pressure chemical ionization tandem mass spectrometry (UPLC-APCI-MS/MS) technique featuring a lower limit of quantitation (LLOQ) as low as 5pg/ml, has been established and validated for the rapid and accurate quantification of eldecalcitol in human plasma samples. Plasma samples were extracted by solid phase extraction (SPE). Stable isotope-labeled compound eldecalcitol-d6 was used as an internal standard (SIL-IS). The detection process was carried out utilizing Multi-Reaction Monitoring (MRM) mode, employing an atmospheric pressure chemical ionization (APCI) source operating in the positive ion modality. The target fragment ion pairs for eldecalcitol and SIL-IS were identified as m/z 508.6 transitioning to 397.4, and m/z 514.6 transitioning to 403.3, respectively. This method was validated regarding selectivity, LLOQ, linearity, accuracy and precision, recovery, matrix effects, dilution reliability, stability, carryover test, and incurred sample reanalysis (ISR). This methodology had been successfully employed to assess the pharmacokinetics (PK) profile of eldecalcitol in a clinical investigation.

Ion exchange chromatography of biotherapeutics: Fundamental principles and advanced approaches.

Ion exchange chromatography (IEX) is an important analytical technique for the characterization of biotechnology-derived products, such as monoclonal antibodies (mAbs) and more recently, cell and gene therapy products such as messenger ribonucleic acid (mRNA) and adeno-associated viruses (AAVs). This review paper first outlines the basic principles and separation mechanisms of IEX for charge variant separation of biotherapeutics, and examines the different elution modes based on salt or pH gradients. It then highlights several recent trends when applying IEX for the characterization of biotechnology-derived products, including: i) the effective use of pH gradients, ii) the improvement of selectivity by using organic solvents in the mobile phase, multi-step gradients, or by combining ion pairing and ion exchange, and iii) the increase in analytical throughput using ultra-short columns or automated screening of conditions. The review also discusses the incorporation of IEX into multidimensional liquid chromatography setups, integrating it with other chromatographic dimensions for the analysis of complex biotherapeutic products. It also covers the coupling of IEX with mass spectrometry (MS), ion mobility spectrometry (IMS), and multi-angle light scattering (MALS) to identify the various species contained in complex biotherapeutic samples. In conclusion, IEX is considered today as an essential technique in the analytical toolbox for the characterization and quality control of biotechnology-derived products. It offers a unique separation mechanism and can be coupled with highly informative detectors, such as MS and MALS.

Physicochemical characterization and nanochemical analysis of ciprofloxacin hydrophobic ion Pairs for enhanced encapsulation in PLGA nanoparticle.

This study investigates the physicochemical transformation of ciprofloxacin (CIP) through hydrophobic ion pairing with five counter ions-sodium oleate, sodium laurate, sodium caprate, disodium pamoate, and sodium deoxycholate-to enhance compatibility with hydrophobic Poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Complexation efficiencies (CE) reached up to 92.26 %, with ciprofloxacin pamoate (CIP-PAM) achieving over 90 % CE at a 1:0.5 M ratio. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses showed reduced crystallinity across all complexes, with CIP-PAM exhibiting an amorphous form. Optical photothermal infrared spectroscopy (O-PTIR) confirmed uniform complexation within particles, while CIP-PAM displayed a broad peak and weak intensity in the 900-1300 cm-1 region, supporting its amorphous nature. Log P values demonstrated increased hydrophobicity for all complexes, with ciprofloxacin oleate (CIP-OLE) showing a 93-fold increase (p < 0.001). In vitro dissociation patterns varied: CIP-OLE maintained steady release in DW (49.7 %) and PBS (32.3 %) over 48 h, whereas CIP-PAM exhibited strong stability in DW (25.2 %) and a contrasting 68.1 % release in PBS, highlighting solvent-dependent dissociation behaviors. PLGA nanoparticles prepared via S/O/W achieved particle sizes under 200 nm, with CIP-PAM showing the highest encapsulation efficiency (63.02 % vs 17.21 % (CIP)). These findings underscore the importance of counter ion selection to optimize CIP compatibility with hydrophobic carriers, providing a basis for improved drug loading of hydrophilic antibiotics.

Defect-Induced Li-Ion Trapping and Hopping in a Grain Boundary-Engineered Li1.3Al0.3Ti1.7(PO4)3 Solid-State Electrolyte.

Understanding lithium-ion dynamics across defect-rich grain boundaries (GBs) is crucial for solid-state electrolytes. This study examines local electronic and structural changes in a Li1.3Al0.3Ti1.7(PO4)3 (LATP) solid electrolyte via X-ray absorption spectroscopy (XAS) and their correlation with ion transport properties. GBs were tailored through conventional isothermal sintering (CIS) and spark plasma sintering (SPS). Ti L2,3-, Ti K-, O K-, and P L2,3-edges from XAS revealed octahedral symmetry in bulk regions of both LATP-CIS and LATP-SPS. However, Ti L2,3-edge spectra in total electron yield mode and Ti K-edge white line intensity shifts in LATP-SPS indicate lower oxidation states and structural distortions due to a significant amorphous GB fraction. Modulations in O K-edge and P L2,3-edge spectra further highlight local structural differences in GB regions of LATP-CIS and LATP-SPS. Electron energy loss spectroscopy (EELS) also reveals variations in Ti L2,3-edge splitting and pre-edge peak intensities, consistent with X-ray absorption near-edge spectroscopy analysis. LATP-SPS exhibits a higher Li content in the GB region than LATP-CIS. The GB ionic conductivity of LATP-SPS (σgb,300K ∼ 1.36 × 10-3 S/cm) is two orders higher than that of LATP-CIS (σgb,300K ∼ 3.84 × 10-5 S/cm), while grain conductivity remains similar. Trapping and hopping enthalpy estimations suggest that trapped Li ions contribute ∼27% of activation energy for LATP-SPS compared to ∼17% for LATP-CIS. Enhanced ion diffusion in polycrystalline LATP GBs is predicted from molecular dynamics simulations, where liquid-like ion pair correlations improve mobility. This work highlights the significant influence of GB-induced structural distortions, probed through XAS and EELS, on the ionic conductivity and charge transport in LATP electrolytes.

Lessons learned on obtaining reliable dynamic properties for ionic liquids.

Ionic liquids are nowadays investigated with respect to their use as electrolytes for high-performance energy storage materials. In this study, we provide a tutorial on how to calculate dynamic properties such as self-diffusion coefficients, ionic conductivities, transference numbers, as well as ion pair and ion cage dynamics, that all play a role in judging the applicability of ionic liquids as electrolytes. For the case of the ionic liquid \ce{[C2C1Im][NTf2]}, we investigate the performance of different force fields. Amongst them are non-polarizable models employing unity charges, a charge-scaled version of a non-polarizable model, a polarizable model and another non-polarizable model with refined Lennard-Jones parameters. We also study the influence of the system size on the dynamic properties. While all studied force field models capture qualitatively correct trends, only the polarizable force field and the non-polarizable force field with refined Lennard-Jones parameters provide quantitative agreement to reference data, making the latter model very attractive for the reason of lower computational costs.

Breaking Aggregation State to Achieve Low‐Temperature Fast Charging of Lithium Metal Batteries

Insufficient ionic conductivity and elevated desolvation energy barrier of electrolytes limit the lithium metal batteries (LMBs) low‐temperature applications. Weakly solvating electrolytes (WSEs), with limited lithium salt dissociation capability, are prone to desolvate and drive anion‐rich aggregates (AGGs). However, significant AGGs result in increased viscosity and low ionic mobility, contributing to battery failure at low temperatures (≤ −20 oC). Here, we propose and achieve a transformation of solvation structures from AGGs to contact ion pairs (CIPs) through modulating the overall solvation capability, thereby achieving the balance between weak Li+ ‐ solvent interactions and desired ion migration kinetics. Remarkly, CIPs‐dominated electrolyte shows a ten‐fold increase in ionic conductivity compared to conventional WSEs. The Li||LiFePO4 (LFP) battery achieves more than 1400 cycles with 86.9% capacity retention at 5 C. The practical 1.2 Ah LFP pouch cell delivered 69% of the capacity at 25 oC when cycled at −40 oC. This strategy for solvation structure transformation in WSEs provides a novel approach for the development of electrolytes for low‐temperature batteries.

Breaking Aggregation State to Achieve Low-Temperature Fast Charging of Lithium Metal Batteries.

Insufficient ionic conductivity and elevated desolvation energy barrier of electrolytes limit the lithium metal batteries (LMBs) low-temperature applications. Weakly solvating electrolytes (WSEs), with limited lithium salt dissociation capability, are prone to desolvate and drive anion-rich aggregates (AGGs). However, significant AGGs result in increased viscosity and low ionic mobility, contributing to battery failure at low temperatures (≤ -20 oC). Here, we propose and achieve a transformation of solvation structures from AGGs to contact ion pairs (CIPs) through modulating the overall solvation capability, thereby achieving the balance between weak Li+ - solvent interactions and desired ion migration kinetics. Remarkly, CIPs-dominated electrolyte shows a ten-fold increase in ionic conductivity compared to conventional WSEs. The Li||LiFePO4 (LFP) battery achieves more than 1400 cycles with 86.9% capacity retention at 5 C. The practical 1.2 Ah LFP pouch cell delivered 69% of the capacity at 25 oC when cycled at -40 oC. This strategy for solvation structure transformation in WSEs provides a novel approach for the development of electrolytes for low-temperature batteries.

Pyridinamide Ion Pairs: Design Principles for Super-Nucleophiles in Apolar Organic Solvents.

A comprehensive analytical protocol combining conductivity, diffusion-ordered NMR (DOSY), and photometric kinetic measurements is employed to analyze the nucleophilic reactivity of pyridinamide ion pairs in low-polarity organic solvents. The association patterns of these systems are found to strongly depend on cation size, with larger cations favoring the formation of cationic triple ion sandwich complexes together with free and highly nucleophilic anions. Kinetic studies using the ionic strength-controlled benzhydrylium method demonstrate that pyridinamide ions exhibit significantly higher nucleophilicities as compared to established organocatalysts, particularly in low-polarity solvents. Nucleophilicities are furthermore found to correlate well with Brønsted basicities measured in water and with Lewis basicities calculated in dichloromethane. Taken together, these findings provide quantitative guidelines for the future design of highly active Lewis base catalysts.

High-Throughput Quantification and Characterization of Dual Payload mRNA/LNP Cargo via Deformulating Size Exclusion and Ion Pairing Reversed Phase Assays.

Therapeutic drugs and multivalent vaccines based on the delivery of mRNA via lipid nanoparticle (LNP) technologies are expected to dominate the biopharmaceutical industry landscape in the coming years. Many of these innovative therapies include several nucleic acid components (e.g., nuclease mRNA and guide RNA) posing unique analytical challenges when monitoring the quantity and quality of each individual payload substance in the formulated LNP. Current methods were optimized for single payload analysis and often lack resolving power needed to investigate nucleic acid mixtures. Ion pairing reversed phase (IP-RP) and size exclusion chromatography (SEC) are increasingly being used to characterize nucleic acids. Here, we studied their application for payload quantification in formulated LNP drug-like products. Using a detergent to disrupt the LNPs, the liberated payloads can be separated on an octadecyl RP column using a fast gradient. Reproducible results were obtained as lipids, and surfactants were efficiently eluted using a high organic solvent wash protocol. Alternatively, we also established an online SEC disruption analysis of the mRNA/LNPs wherein an alcohol and detergent containing a mobile phase was applied. Such conditions universally deformulated all tested LNP samples, indicating that a 5 min-long SEC separation can be used as a high-throughput platform method. In both approaches, the measurements facilitate a multiattribute analysis. Apart from quantitation, the characterization of specific impurities is achieved: IP-RP reveals mRNA-lipid adducts, while SEC informs on size variants, which in turn reduces a laboratory's analytical workload. These easy-to-adopt LC-based assays are expected to fortify the analytical toolbox for emerging gene therapeutics.

Transient methods for understanding the properties of strongly oxidizing radicals.

This review discusses the properties of strongly oxidizing radicals in organic and aqueous media and highlights the challenges in obtaining accurate values of their reduction potentials. Transient redox equilibrium methods based on the use of strong photooxidants or initiated by pulse radiolysis are shown to provide versatile approaches for decoupling electron transfer reactions from follow-up reactivity of unstable radical species, resulting in accurate values of reduction potentials of very positive couples, including some solvent radical cations. We also show that correlations of reduction potentials with Hammett ∑σ+p parameters, as well as gas phase ionization potentials, can be used to estimate the redox properties of unknown couples within a homologous series of compounds. The effects of ion pairing and hemicolligation on redox properties of organic and inorganic radicals are also discussed.

Ru(II)-Based Multitopic Hosts for Fullerene Binding: Impact of the Anion in the Recognition Process.

The development of multitopic hosts for fullerene recognition based on nonplanar corannulene (C20H10) structures presents challenges, primarily due to the requirement for synergistic interactions with multiple units of this polycyclic aromatic hydrocarbon. Moreover, increasing the number of corannulene groups in a single chemical structure while avoiding the cost of increasing flexibility has been scarcely explored. Herein, we report the synthesis of a family of multitopic Ru(II)-polypyridyl complexes bearing up to six units of corannulene arranged by pairs, offering a total of three molecular tweezers. All of them are fixed by the central atom and organized in an octahedral structure. Their fullerene recognition capabilities have been thoroughly demonstrated toward C60 and C70 showing that they can reasonably accommodate up to three fullerenes per host in a noncooperative manner. There are, however, some features that diverge from comparable hosts in the literature, such as the low value of several association constants. This behavior, supported by theoretical studies, is attributed to the presence of two noninnocent BAr4F anions that interfere with the supramolecular binding through ion pair formation. These findings highlight the crucial role of selecting compatible ionic species in supramolecular host design as they can significantly influence the recognition process.

Complete Polar Lipid Profile of Kefir Beverage by Hydrophilic Interaction Liquid Chromatography with HRMS and Tandem Mass Spectrometry

Kefir, a fermented milk product produced using kefir grains, is a symbiotic consortium of bacteria and yeasts responsible for driving the fermentation process. In this study, an in-depth analysis of kefir’s lipid profile was conducted, with a focus on its phospholipid (PL) content, employing liquid chromatography with high-resolution mass spectrometry (LC-HRMS). Nearly 300 distinct polar lipids were identified through hydrophilic interaction liquid chromatography (HILIC) coupled with electrospray ionization (ESI) and Fourier-transform orbital-trap MS and linear ion-trap tandem MS/MS. The identified lipids included phosphatidylcholines (PCs), lyso-phosphatidylcholines (LPCs), phosphatidylethanolamines (PEs) and lyso-phosphatidylethanolamines (LPEs), phosphatidylserines (PSs), phosphatidylglycerols (PGs), and phosphatidylinositols (PIs). The presence of lysyl-phosphatidylglycerols (LyPGs) was identified as a key finding, marking a lipid class characteristic of Gram-positive bacterial membranes. This discovery highlights the role of viable bacteria in kefir and underscores its probiotic potential. The structural details of minor glycolipids (GLs) and glycosphingolipids (GSLs) were further elucidated, enriching the understanding of kefir’s lipid complexity. Fatty acyl (FA) composition was characterized using reversed-phase LC coupled with tandem MS. A mild epoxidation reaction with meta-chloroperoxybenzoic acid (m-CPBA) was performed to pinpoint double-bond positions in FAs. The dominant fatty acids were identified as C18:3, C18:2, C18:1, C18:0 (stearic acid), C16:0 (palmitic acid), and significant levels of C14:0 (myristic acid). Additionally, two isomers of FA 18:1 were distinguished: ∆9-cis (oleic acid) and ∆11-trans (vaccenic acid). These isomers were identified using diagnostic ion pairs, retention times, and accurate m/z values. This study provides an unprecedented level of detail on the lipid profile of kefir, shedding light on its complex composition and potential nutritional benefits.