Adduct-ion formation in trapped ion mobility spectrometry as a potential tool for studying molecular structures and conformations

Zietek, Barbara M.; Mengerink, Ynze; Jordens, Jan; Somsen, Govert W.; Kool, Jeroen; Honing, Maarten

doi:10.1007/s12127-017-0227-6

Cited by 26 publications

(40 citation statements)

References 45 publications

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“…bands D and L) which are indicative of less tightly folded conformers, similar to those previously observed in nESI‐TIMS experiments on DNA structures . Sodium adduction has been shown to stabilize both larger and smaller structures in gas‐phase analysis of small molecules and peptides …”

Section: Resultssupporting

confidence: 77%

Single‐stranded DNA structural diversity: TAGGGT from monomers to dimers to tetramer formation

Porter

Chapagain

Fernandez‐Lima

2019

Rapid Comm Mass Spectrometry

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Rationale DNA quadruplex structures have emerged as novel drug targets due to their role in preventing abnormal gene transcription and maintaining telomere stability. Trapped Ion Mobility Spectrometry–Mass Spectrometry (TIMS–MS), combined with theoretical modeling, is a powerful tool for studying the kinetic intermediates of DNA complexes formed in solution and interrogated in the gas phase after desolvation. Methods A TAGGGT ssDNA sequence was purchased and studied in 10 mM ammonium acetate using nanospray electrospray ionization (nESI)‐TIMS‐MS in positive and negative ion mode. Collisional cross section (CCS) profiles were measured using internal calibration (Tune Mix). Theoretical structures were proposed based on molecular dynamics, charge location and geometry optimization for the most intense IMS bands based on the number of TAGGGT units, adduct form and charge states. Results A distribution of monomeric, dimeric and tetrameric TAGGGT structures were formed in solution and separated in the gas phase based on their mobility and m/z value (e.g., [M + 2H]+2, [2M + 3H]+3, [M – 2H]−2, [2M – 3H]−3, [4M + 4H]+4, [4M + 3H + NH4]+4, [4M + 2H + 2NH4]+4 and [4M + H + 3NH4]+4). The high mobility resolution of the TIMS‐MS analyzer permitted the observation of multiple CCS bands per molecular ion form. Comparison with theoretical candidate structures suggests that monomeric TAGGGT species are stabilized by A‐T and G+‐G interactions, with the size of the conformer influenced by the proton location. In the case of the TAGGGT quadruplex, the protonated species displayed a broad CCS distribution, while six discrete conformers were stabilized by the presence of ammonium ions (n = 1–3). Conclusions This is the first observation of multiple conformations of TAGGGT complexes (n = 1, 2 and 4) in 10 mM ammonium acetate. Candidate structures with intramolecular interactions of the form of G+‐G and traditional A‐T base pairing agreed with the experimental trends. Our results demonstrate the structural diversity of TAGGGT monomers, dimers and tetramers in the gas phase beyond the previously reported solution structure, using 10 mM ammonium acetate to replicate biological conditions.

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Section: Resultssupporting

confidence: 77%

Single‐stranded DNA structural diversity: TAGGGT from monomers to dimers to tetramer formation

Porter

Chapagain

Fernandez‐Lima

2019

Rapid Comm Mass Spectrometry

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“…In similar applications, SRs were injected in the ESI solution with the sample and not in the buffer gas to, citing only a few examples: Examine host guest interactions to design potential molecular biosensors using IMS‐MS Separate pharmaceutical molecules and tetrahydrocannabinol and its isomer cannabidiol by adduction with H + , Cs + , Li + , Ag + , and Na + achieving structural assignment of molecular isomers and analyte conformations Recognize peptidoglycans by downsizing the binding sites of a peptidoglycan recognition protein into tripeptides.…”

Section: Applications Of Mobility Shifts Upon Injection Of Buffer Gasmentioning

confidence: 99%

Buffer gas additives (modifiers/shift reagents) in ion mobility spectrometry: Applications, predictions of mobility shifts, and influence of interaction energy and structure

Fernandez‐Maestre

2018

J Mass Spectrom

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Ion mobility spectrometry (IMS) is an analytical technique used for fast and sensitive detection of illegal substances in customs and airports, diagnosis of diseases through detection of metabolites in breath, fundamental studies in physics and chemistry, space exploration, and many more applications. Ion mobility spectrometry separates ions in the gas-phase drifting under an electric field according to their size to charge ratio. Ion mobility spectrometry disadvantages are false positives that delay transportation, compromise patient's health and other negative issues when IMS is used for detection. To prevent false positives, IMS measures the ion mobilities in 2 different conditions, in pure buffer gas or when shift reagents (SRs) are introduced in this gas, providing 2 different characteristic properties of the ion and increasing the chances of right identification. Mobility shifts with the introduction of SRs in the buffer gas are due to clustering of analyte ions with SRs. Effective SRs are polar volatile compounds with free electron pairs with a tendency to form clusters with the analyte ion. Formation of clusters is favored by formation of stable analyte ion-SR hydrogen bonds, high analytes' proton affinity, and low steric hindrance in the ion charge while stabilization of ion charge by resonance may disfavor it. Inductive effects and the number of adduction sites also affect cluster formation. The prediction of IMS separations of overlapping peaks is important because it simplifies a trial and error procedure. Doping experiments to simplify IMS spectra by changing the ion-analyte reactions forming the so-called alternative reactant ions are not considered in this review and techniques other than drift tube IMS are marginally covered.

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“…The addition of metal cations has been shown to be a valuable approach in forcing molecules into more rigid conformations, thus introducing ‘detectable” differences in the CCS and allowing the IMS separation of different conformers (potamers) . More specifically, previous studies have reported improved mobility separation upon the addition of Ag, Li and Cs cations, which are the same metal cations that were used in this study. It was assumed that the size of the counter ions (radius of Li = 76, Ag = 138, Cs = 167 picometers) can improve the separation of isomers in the ion mobility cells.…”

Section: Resultsmentioning

confidence: 85%

“…The use of adduct ions has been proven to be such an alternative for the separation of structural and even stereo‐isomers . As an example, Na, Li, Ag or even Cs coordinates to molecules with different conformers of the isomeric forms, leading to an improved separation.…”

Section: Introductionmentioning

confidence: 99%

“…As an example, Na, Li, Ag or even Cs coordinates to molecules with different conformers of the isomeric forms, leading to an improved separation. Moreover, the ions can coordinate at different positions within one molecule and give rise to multiple peaks in the mobilogram, which can generate insight into the different complexation mechanisms . As an example, our previously validated approach led to the separation of the isobaric and structural isomers of tetrahydrocannabinol and cannabidiol in a Trapped ion mobility spectroscopy (TIMS) setup .…”

Section: Introductionmentioning

confidence: 99%

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Adduct ion formation as a tool for the molecular structure assessment of ten isomers in traveling wave and trapped ion mobility spectrometry

Hadavi

Lange

Jordens

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale The separation of isomeric compounds with major differences in their physiochemical and pharmacokinetic properties is of particular importance in pharmaceutical R&D. However, the structural assessment and separation of these compounds with current analytical techniques and methods are still a challenge. In this study, we describe strategies to separate the various structural and stereo‐isomers. Methods The separation of ten structural and stereo‐isomers was investigated using Trapped and Travelling Wave ion mobility spectrometry (TIMS and TWIMS). Different strategies including adduct ion formation with Na, Li, Ag and Cs as well as fragmentation before and after the ion mobility cell were applied to separate the isomeric compounds. Results All the counter ions (in particular Na) strongly coordinated with the test analytes in all the IMS systems. The highest resolving power was achieved for the sodium and lithium adducts using TIMS‐time‐of‐flight (TOF). However, some separation was attained on a Synapt HDMS system with its unique potential to monitor the ion mobility of the product ions. The elution order of the adduct ions was the same in all instruments, in which, unexpectedly, the para‐substituted isomer of the [M + Na]+ species had the lowest collision cross section followed by the meta‐ and ortho‐isomers. Conclusions The formation of adduct ions could facilitate the separation of structural and even stereo‐isomers by generating different molecular conformations. In addition, fragmenting isomers before or after the ion mobility cell is a valuable strategy to separate and also to assess the structures of adducts and different conformers.

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Adduct-ion formation in trapped ion mobility spectrometry as a potential tool for studying molecular structures and conformations

Cited by 26 publications

References 45 publications

Single‐stranded DNA structural diversity: TAGGGT from monomers to dimers to tetramer formation

Single‐stranded DNA structural diversity: TAGGGT from monomers to dimers to tetramer formation

Buffer gas additives (modifiers/shift reagents) in ion mobility spectrometry: Applications, predictions of mobility shifts, and influence of interaction energy and structure

Adduct ion formation as a tool for the molecular structure assessment of ten isomers in traveling wave and trapped ion mobility spectrometry

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