Mass Spectrometry Directed Structural Elucidation of Isomeric [2 + 2] Photocycloadducts.

[2 + 2] Photocycloaddition reactions are powerful tools for synthetic chemistry. However, analysis of the head-to-head or head-to-tail conformation of the resulting cycloadducts is often challenging by conventional spectroscopic methods. Herein, we report the analysis of coumarin and styrylpyrene cycloadducts by cyclic ion-mobility tandem mass spectrometry (cIM-MS/MS) to characterize the regioisomeric products of this important class of photoresponsive groups.

What Drives the Vehicle Mechanism? Protonation Isomer Interconversion of Arylamine Derivatives Probed with Solvent-Mediated Kinetics.

Reactions with mobile protons occur under electrospray ionization (ESI) in many applications of mass spectrometry. Understanding how protonation isomers (protomers) form and how molecular structure influences protomer interconversion provides fundamental insight into ESI mechanisms, which can then be exploited to rationalize ion mobility and ion activation processes for robust analyte detection. Using ten arylamine protomer systems, this paper establishes the key substrate properties that influence protomer isomerism.

Electrostatically tuning radical addition and atom abstraction reactions with distonic radical ions.

Although electrostatic catalysis can enhance the kinetics and selectivity of reactions to produce greener synthetic processes, the highly directional nature of electrostatic interactions has limited widespread application. In this study, the influence of oriented electric fields (OEF) on radical addition and atom abstraction reactions are systematically explored with ion-trap mass spectrometry using structurally diverse distonic radical ions that maintain spatially separated charge and radical moieties. When installed on rigid molecular scaffolds, charged functional groups lock the magnitude and orientation of the internal electric field with respect to the radical site, creating an OEF which tunes the reactivity across the set of gas-phase carbon-centred radical reactions.

Don't forget the : double bond isomerism radical-acetylene growth reactions affect the primary stages of PAH and soot formation.

In combustion, acetylene is a key species in molecular-weight growth reactions that form polycyclic aromatic hydrocarbons (PAHs) and ultimately soot particles. Radical addition to acetylene generates a vinyl radical intermediate, which has both and isomers. This isomerism can lead to profound changes in product distributions that are as yet insufficiently investigated.

Metal Polycation Adduction to Lipids Enables Superior Ion Mobility Separations with Ultrafast Ozone-Induced Dissociation.

Specific lipid isomers are functionally critical, but their structural rigidity and usually minute geometry differences make separating them harder than other biomolecules. Such separations by ion mobility spectrometry (IMS) were recently enabled by new high-definition methods using dynamic electric fields, but major resolution gains are needed. Another problem of identifying many isomers with no unique fragments in ergodic collision-induced dissociation (CID) was partly addressed by the direct ozone-induced dissociation (OzID) that localizes the double bonds, but a low reaction efficiency has limited the sensitivity, dynamic range, throughput, and compatibility with other tools.

Polystyrene Chain Geometry Probed by Ion Mobility Mass Spectrometry and Molecular Dynamics Simulations.

Polystyrene (PS) is a thermoplastic polymer commonly used in various applications due to its bulk properties. Designing functional polystyrenes with well-defined structures for targeted applications is of significant interest due to the rigid and apolar nature of the polymer chain. Progress is hindered to date by the limitations of current analytical methods in defining the atomistic-level folding of the polymer chain.

Cross-Validation of Lipid Structure Assignment Using Orthogonal Ion Activation Modalities on the Same Mass Spectrometer.

The onset and progression of cancer is associated with changes in the composition of the lipidome. Therefore, better understanding of the molecular mechanisms of these disease states requires detailed structural characterization of the individual lipids within the complex cellular milieu. Recently, changes in the unsaturation profile of membrane lipids have been observed in cancer cells and tissues, but assigning the position(s) of carbon-carbon double bonds in fatty acyl chains carried by membrane phospholipids, including the resolution of lipid regioisomers, has proven analytically challenging.

Cyclic tachyplesin I kills proliferative, non-proliferative and drug-resistant melanoma cells without inducing resistance.

Acquired drug resistance is the major cause for disease recurrence in cancer patients, and this is particularly true for patients with metastatic melanoma that carry a BRAF mutation. To address this problem, we investigated cyclic membrane-active peptides as an alternative therapeutic modality to kill drug-tolerant and resistant melanoma cells to avoid acquired drug resistance. We selected two stable cyclic peptides (cTI and cGm), previously shown to have anti-melanoma properties, and compared them with dabrafenib, a drug used to treat cancer patients with the BRAF mutation.

Evidence for within-species transition between drought response strategies in Nicotiana benthamiana.

Nicotiana benthamiana is predominantly distributed in arid habitats across northern Australia. However, none of six geographically isolated accessions shows obvious xerophytic morphological features. To investigate how these tender-looking plants withstand drought, we examined their responses to water deprivation, assessed phenotypic, physiological, and cellular responses, and analysed cuticular wax composition and wax biosynthesis gene expression profiles.

Observation of Solvent-Dependence in the Mechanism of Neutral-Catalyzed Isomerization of -Aminobenzoic Acid Protomers.

Proton-transfer reactions are commonplace during electrospray ionization (ESI) mass spectrometry experiments and are often responsible for imparting charge to analyte molecules. Multiple protonation-site isomers (protomers) can arise for polyfunctional molecules and these isomers can interconvert via solvent-mediated proton transfer reactions during various stages of the ESI process. Studying the populations and interconversion of protonation isomers provides key insight into the ESI process, ion-molecule interactions, and ion dissociation mechanisms.

Gas-Phase Phenyl Radical + O Reacts via a Submerged Transition State.

In the gas-phase chemistry of the atmosphere and automotive fuel combustion, peroxyl radical intermediates are formed following O addition to carbon-centered radicals which then initiate a complex network of radical reactions that govern the oxidative processing of hydrocarbons. The rapid association of the phenyl radical-a fundamental radical related to benzene-with O has hitherto been modeled as a barrierless process, a common assumption for peroxyl radical formation. Here, we provide an alternate explanation for the kinetics of this reaction by deploying double-hybrid density functional theory (DFT), at the DSD-PBEP86-D3(BJ)/aug-cc-pVTZ level of theory, and locate a submerged adiabatic transition state connected to a prereaction complex along the reaction entrance pathway.

Deep Characterisation of the sn-Isomer Lipidome Using High-Throughput Data-Independent Acquisition and Ozone-Induced Dissociation.

In recent years there has been a significant interest in the development of innovative lipidomics techniques capable of resolving lipid isomers. To date, methods applied to resolving sn-isomers have resolved only a limited number of species. We report a workflow based on ozone-induced dissociation for untargeted characterisation of hundreds of sn-resolved glycerophospholipid isomers from biological extracts in under 20 min, coupled with an automated data analysis pipeline.

Revolutions in Lipid Isomer Resolution: Application of Ultrahigh-Resolution Ion Mobility to Reveal Lipid Diversity.

Many families of lipid isomers remain unresolved by contemporary liquid chromatography-mass spectrometry approaches, leading to a significant underestimation of the structural diversity within the lipidome. While ion mobility coupled to mass spectrometry has provided an additional dimension of lipid isomer resolution, some isomers require a resolving power beyond the capabilities of conventional platforms. Here, we present the application of high-resolution traveling-wave ion mobility for the separation of lipid isomers that differ in (i) the location of a single carbon-carbon double bond, (ii) the stereochemistry of the double bond ( or ), or, for glycerolipids, (iii) the relative substitution of acyl chains on the glycerol backbone (-position).

9-Azahomocubane.

Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g., a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine.

Isomer-Resolved Mass Spectrometry Imaging of Acidic Phospholipids.

The biological functions of lipids are entirely dependent on their molecular structures with even small changes in structure─such as different sites of unsaturation─providing critical markers for changes in the underlying metabolism. Conventional mass spectrometry imaging (MSI) approaches, however, face the twin challenges of mixture and structural complexity and are typically unable to differentiate lipid isomers that differ only in the position(s) of carbon-carbon double bonds. Recent coupling of ozone-induced dissociation (OzID) with matrix-assisted laser desorption/ionization (MALDI)-MSI has demonstrated the potential to map changes in individual double-bond isomers, thus enabling visualization of the modulation in lipid desaturation in adjacent tissue types.

Ozone-enabled fatty acid discovery reveals unexpected diversity in the human lipidome.

Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds.

Gas-Phase Internal Proton-Transfer of Protonated -Aminobenzoic Acid Catalyzed by One Methanol Molecule.

Electrospray ionization (ESI) is used to deliver analytes for mass analysis across a huge range of mass spectrometry applications. Despite its ubiquitous application and many mechanistic investigations, it remains that a fundamental understanding of ESI processes is not complete. In particular, all the factors that influence the populations of protonation isomers are elusive such that it remains a challenge to optimize experimental conditions to favor one isomer over another.

Diastereomer Resolution of M L Coordination Cages by Ultra-High-Resolution Ion-Mobility Mass Spectrometry.

Coordination cages can be used for enantio- and regioselective catalysis and for the selective sensing and separation of isomeric guest molecules. Here, stereoisomers of a family of coordination cages are resolved using ultra-high-resolution cyclic ion-mobility mass spectrometry (cIM-MS). The observed ratio of diastereomers is dependent on both the metal ion and counter ion.

Characterization of Triacylglycerol Estolide Isomers Using High-Resolution Tandem Mass Spectrometry with Nanoelectrospray Ionization.

Triacylglycerol estolides (TG-EST) are biologically active lipids extensively studied for their anti-inflammatory and anti-diabetic properties. In this work, eight standards of TG-EST were synthesized and systematically investigated by nanoelectrospray tandem mass spectrometry. Mass spectra of synthetic TG-EST were studied with the purpose of enabling the unambiguous identification of these lipids in biological samples.

1-Azahomocubane.

Highly strained cage hydrocarbons have long stood as fundamental molecules to explore the limits of chemical stability and reactivity, probe physical properties, and more recently as bioactive molecules and in materials discovery. Interestingly, the nitrogenous congeners have attracted much less attention. Previously absent from the literature, azahomocubanes, offer an opportunity to investigate the effects of a nitrogen atom when incorporated into a highly constrained polycyclic environment.

Establishing carbon-carbon double bond position and configuration in unsaturated fatty acids by gas-phase infrared spectroscopy.

Fatty acids are an abundant class of lipids that are characterised by wide structural variation including isomeric diversity arising from the position and configuration of functional groups. Traditional approaches to fatty acid characterisation have combined chromatography and mass spectrometry for a description of the composition of individual fatty acids while infrared (IR) spectroscopy has provided insights into the functional groups and bond configurations at the bulk level. Here we exploit universal 3-pyridylcarbinol ester derivatization of fatty acids to acquire IR spectra of individual lipids as mass-selected gas-phase ions.

Identification of Carbon-Carbon Double Bond Stereochemistry in Unsaturated Fatty Acids by Charge-Remote Fragmentation of Fixed-Charge Derivatives.

Separation and identification of fatty acid (FA) isomers in biological samples represents a challenging problem for lipid chemists. Notably, FA regio- and stereo-isomers differing in the location or () geometry of carbon-carbon double bonds are often incompletely separated and ambiguously assigned in conventional chromatography-mass spectrometry analyses. To address this challenge, FAs have been derivatized with the charge-switch derivatization reagents -methyl-pyridinium-3-methanamine and -(4-aminomethylphenyl)pyridinium and subjected to reversed-phase liquid chromatography-tandem mass spectrometry.

Identification of Monomethyl Branched-Chain Lipids by a Combination of Liquid Chromatography Tandem Mass Spectrometry and Charge-Switching Chemistries.

While various mass spectrometric approaches have been applied to lipid analysis, unraveling the extensive structural diversity of lipids remains a significant challenge. Notably, these approaches often fail to differentiate between isomeric lipids─a challenge that is particularly acute for branched-chain fatty acids (FAs) that often share similar (or identical) mass spectra to their straight-chain isomers. Here, we utilize charge-switching strategies that combine ligated magnesium dications with deprotonated fatty acid anions.

UV photodissociation action spectra of protonated formylpyridines.

The first ππ* transition for protonated 2-, 3-, and 4-formylpyridine (FPH) (m/z 108) is investigated by mass spectrometry coupled with photodissociation action spectroscopy at room temperature and 10 K. The photoproduct ions are detected over 35 000-43 000 cm, and the major product channel for 3-FPH and 4-FPH is the loss of CO forming protonated pyridine at m/z 80. For 2-FPH, the CO loss product is present but a more abundant photoproduct arises from the loss of CHO to form m/z 78.