Alina Begley


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Begley

First Name

Alina

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0000-0003-4649-3173

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Publications 1 - 10 of 10
  • Low-temperature Plasma Chemistry for Mass Spectrometry and Beyond
    Item type: Doctoral Thesis
    Begley, Alina (2024)
    Dielectric barrier discharge ionization (DBDI) is a simple yet powerful technique to generate intact ions for mass spectrometry (MS) and has been commercialized for applications from measuring car exhaust in real time to food safety analysis. The DBDI source forms a type of low-temperature plasma which generates reactive species. When these react with organic molecules, they form ions which can be detected by MS. However, the plasma chemistry of the DBD is not fully understood and can lead to unusual reaction products that are unexpected and unwanted for MS applications. While most plasma sources are operated with a noble gas (Ar or He), the DBDI source can operate with any gas and be coupled directly to the mass spectrometer. While this has advantages like higher ion transmission and cost-effectiveness, it can lead to more complex plasma chemistry. This is because unlike atomic noble gases He or Ar which form a limited number of reactive species, molecular gases have rovibrational states and their atomic species are highly reactive. In this thesis, we primarily studied the reactive species of the DBDI source operated with nitrogen, which is less well characterized than helium or air. It was discovered that near the ignition voltage of the plasma, aromatic hydrocarbons like benzene formed the radical cation [M]•+, as expected. However, at elevated operating voltages, an unusual reaction resulted in the replacement of an aromatic carbon with a nitrogen to yield pyridinium ions [M-C+N]+, i.e. a nitrogen-replacement product. The addition of nitrogen to yield the product [M+N]+, i.e. a nitrogen-addition product, was also observed. A combination of MS, kinetics modelling, and DFT calculations revealed that electronically excited state N-atoms N(2P) can react with toluene ions to directly replace an aromatic carbon atom in the aromatic ring to form [M-C+N]+. The formation of N(2P) in the DBDI at higher operating voltages (well above the ignition voltage) was further confirmed with optical emission spectroscopy. The nitrogen-addition product was attributed to multiple reaction pathways: reaction of neutral toluene with N2+ or N4+ or reaction of ground-state N(4S) atoms with toluene ions. Near the ignition or low voltage (2.4 kVpp), Nx+ (x=2, 3, 4), N2*, NO* play dominant roles, while at a higher operating voltage (3.4 kVpp), excited state N-atoms N(2P) form and N(4S), N2*, NO* are elevated. Using the newly gained fundamental understanding of the reactive nitrogen species in the DBDI source, a method was developed to discriminate between aromatic hydrocarbon isomers such as methylbenzenes (C8H10) and ethylbenzenes (C9H12), which cannot usually be distinguished by mass spectrometry or tadem MS alone. At low operating voltage (2.4 kVpp), the intact mass of the isomer could be identified as [M]•+. At higher operating voltage the [M+N]+ product was formed. Fragmenting the [M+N]+ product with tandem-MS led to neutral losses HCN and xCN, which corresponded to N-addition to an aromatic carbon or the substituent x (x=CH3, CH2CH3, Cl, etc.), respectively. The greater the number of substituents x, the greater the relative loss of xCN to HCN. For regioisomers that had the same substituent x, the ratio of xCN to HCN corresponded to how accessible the aromatic carbon was, thereby allowing identification of the isomer based on collision induced dissociation (CID) fragmentation of the [M+N]+ product. The use of the reactive nitrogen species was expanded beyond mass spectrometry to surface science. By placing a monolayer graphene in front of the DBD in controlled nitrogen atmosphere, nitrogen atoms could be doped into the graphene lattice. Short treatment times (30 s) resulted in a moderate degree of damage (ID/IG=1.2) and an increase in the N-atom (pyrrolic) and O atom (mixed) content. At long treatment times (20 min), the treated area increased radially and the graphene was destroyed. Overall, N-atom content increased with increasing operating voltage of the DBD source. When the graphene was treated with only neutral reactive nitrogen species, the N-atom content and type remained unchanged. Therefore, the primary reactive species resulting in pyrrolic N-doping from the DBD were found to be neutrals such as N(4S) and possibly N(2P). The DBD can also be operated with helium gas to form a plasma-jet and mimic devices currently on the market for biomedical applications. Biomedical low-temperature plasmas use reactive species to modulate biological process (redox biology) and have had success in clinical trials to accelerate wound healing. However, their effect on physiologically relevant concentrations of proteins has led to conflicting results ranging from peptide fragmentation, oxidation, to ag-gregation. Using the experience of characterizing the nitrogen DBDI, the He DBD was characterized and was shown to form gas-phase atomic oxygen O(3P), O3, O2- (among others) downstream from the jet with oxygen from the surrounding air. When the He DBD is directed at an aqueous solution, the reactive species impinge on the liquid surface and form solution-phase reactive oxygen species (ROS) such as OH• and O2•-. Treating solutions of peptide or protein results in extensive oxidation by the ROS. Through a series of mass spectrometry experiments, it was shown that short peptides oxidize and remain solvated independent of their concentration. However, conformational changes of oxidized longer peptides and proteins result in time- and concentration-dependent formation of insoluble aggregates. This finding has implications for the safety of low temperature plasmas in biological applications. This thesis investigates the plasma chemistry of the DBDI source and shows that a fundamental understanding of the reactive species formed can lead to heir successful application in mass spectrometry and beyond.
  • Low-temperature plasma jet treatment generates reactive oxygen species in solution that leads to peptide oxidation and protein aggregation
    Item type: Journal Article
    Begley, Alina; Oganesyan, Irina; Mrdenovic, Dusan; et al. (2024)
    Journal of Physics D: Applied Physics
    Low-temperature plasma (LTPs) jets are FDA-approved medical devices to remove cancerous tissue and aid in wound healing. However, reports on their reaction with proteins are conflicting, ranging from fragmentation, oxidation, aggregation, or a combination thereof. In this study we bridge the gap between plasma-treatment of short peptides to proteins at physiologically relevant concentrations. The LTP in this study is based on a helium dielectric barrier discharge (DBD) that forms a plasma-jet, which is directed at the solution without direct contact with the plasma, and results in the formation of reactive oxygen species (ROS) OH• and O2•- in solution. The longer the solution is treated, the more solution-phase ROS form. Treating peptide- and protein-containing solutions leads to extensive oxidation. The ROS led to the same oxidative modifications for peptide M with increasing chain length (9, 18, 37, 76 amino acids), which could be identified with high-resolution mass spectrometry. Oxidized species M+xO led to conformational changes such as compaction and elongation, while the unmodified peptide M remained unaltered, as found by ion mobility spectrometry and size exclusion chromatography. For proteins at high concentration, insoluble aggregates formed and could be identified by UV/Vis light scattering and atomic force microscopy. The formation of aggregates is dependent on the amino acid chain length, the peptide concentration, and the time for aggregate formation. These findings highlight the importance of both peptide chain length and concentration in determining the fate of peptides following the exposure to LTP, while also offering valuable insights for the field of plasma medicine.
  • Temperature-controlled electrospray ionization mass spectrometry as a tool to study collagen homo- and heterotrimers
    Item type: Journal Article
    Köhler, Martin; Marchand, Adrien; Hentzen, Nina B.; et al. (2019)
    Chemical Science
    Collagen model peptides are useful for understanding the assembly and structure of collagen triple helices. The design of self-assembling heterotrimeric helices is particularly challenging and often affords mixtures of non-covalent assemblies that are difficult to characterize by conventional NMR and CD spectroscopic techniques. This can render a detailed understanding of the factors that control heterotrimer formation difficult and restrict rational design. Here, we present a novel method based on electrospray ionization mass spectrometry to investigate homo- and heterotrimeric collagen model peptides. Under native conditions, the high resolving power of mass spectrometry was used to access the stoichiometric composition of different triple helices in complex mixtures. A temperature-controlled electrospray ionization source was built to perform thermal denaturation experiments and provided melting temperatures of triple helices. These were found to be in good agreement with values obtained from CD spectroscopic measurements. Importantly, for mixtures of coexisting homo- and heterotrimers, which are difficult to analyze by conventional methods, our technique allowed for the identification and monitoring of the unfolding of each individual species. Their respective melting temperatures could easily be accessed in a single experiment, using small amounts of sample.
  • Aptapaper ─ An Aptamer-Functionalized Glass Fiber Paper Platform for Rapid Upconcentration and Detection of Small Molecules
    Item type: Journal Article
    Martinez Jarquin, Sandra; Begley, Alina; Lai, Yin-Hung; et al. (2022)
    Analytical Chemistry
    We tested a paper-based platform (“Aptapaper”) for the upconcentration and analysis of small molecules from complex matrices for two well-characterized aptamers, quinine and serotonin binding aptamers (QBA and SBA, respectively). After incubating the aptapaper in conditions that ensure correct aptamer folding, the aptapaper was used to upconcentrate target analytes from complex matrices. Aptapaper was rinsed, dried, and the target analyte was detected immediately or up to 4 days later by paper spray ionization coupled to high resolution mass spectrometry (PS-MS). The minimum concentrations detectable were 81 pg/mL and 1.8 ng/mL for quinine and serotonin, respectively, from 100 mM AmAc or water. Complementary characterization of the QBA aptapaper system was performed using an orthogonal fluorescence microscopy method. Random adsorption was analyte-specific and observed for quinine, but not serotonin. This aptapaper approach is a semi-quantitative (10-20% RSD) platform for upconcentration of small metabolites by mass spectrometry.
  • Discriminating alkylbenzene isomers with tandem mass spectrometry using a dielectric barrier discharge ionization source
    Item type: Journal Article
    Begley, Alina; Zenobi, Renato (2023)
    Journal of Mass Spectrometry
    Soft ambient ionization sources generate reactive species that interact with analyte molecules to form intact molecular ions, which allows rapid, sensitive, and direct identification of the molecular mass. We used a dielectric barrier discharge ionization (DBDI) source with nitrogen at atmospheric pressure to detect alkylated aromatic hydrocarbon isomers (C8 H10 or C9 H12 ). Intact molecular ions [M]•+ were detected at 2.4 kVpp , but at increased voltage (3.4 kVpp ), [M + N]+ ions were formed, which could be used to differentiate regioisomers by collision-induced dissociation (CID). At 2.4 kVpp , alkylbenzene isomers with different alkyl-substituents could be identified by additional product ions: ethylbenzene and -toluene formed [M-2H]+ , isopropylbenzene formed abundant [M-H]+ , and propylbenzene formed abundant C7 H7+ . At an operating voltage of 3.4 kVpp , fragmentation of [M + N]+ by CID led to neutral loss of HCN and CH3 CN, which corresponded to steric hindrance for excited state N-atoms approaching the aromatic ring (C-H). The ratio of HCN to CH3 N loss (interday relative standard deviation [RSD] < 20%) was distinct for ethylbenzene and ethyltoluene isomers. The greater the number of alkyl-substituents (C-CH3 ) and the more sterically hindered (meta > para > ortho) the aromatic core, the greater the loss of CH3 CN relative to HCN was.
  • Nitrogen-doping graphene at ambient conditions with N2-DBD-plasma and the role of neutral species
    Item type: Journal Article
    Begley, Alina; Bartolomeo, Giovanni Luca; Abbott, Daniel F.; et al. (2024)
    Plasma Processes and Polymers
    We doped nitrogen into monolayer graphene using reactive nitrogen species from a dielectric barrier discharge (DBD). After 30 s of treatment, the graphene monolayer had a moderate degree of damage (I-D/I-G = 1.2) and an increase in the N-atom (pyrrolic) and O-atom (mixed) content. During long treatment times (20 min), the treated area increased radially and the graphene was destroyed. Overall, the N-atom content increased with increasing operating voltage of the DBD source. When the graphene was treated with only neutral reactive nitrogen species, the N-atom content and type remained unchanged. Therefore, we hypothesize that the primary reactive species resulting in pyrrolic N-doping from the DBD are neutrals such as N(S-4) and possibly N(P-2).
  • Oxidative aggregation of hemoglobin–a mechanism for low-temperature plasma-mediated wound healing
    Item type: Journal Article
    Oganesyan, Irina; Begley, Alina; Mrđenović, Dušan; et al. (2024)
    Journal of Physics D: Applied Physics
    Plasma medicine is a field that utilizes reactive species generated from atmospheric low-temperature plasmas for applications such as sterilization, blood coagulation, and cancer therapy. Commercial plasma devices are available for wound healing, but research on the chemical modifications induced by these plasmas is scarce. This study explores the chemical modifications in hemoglobin when exposed to a helium plasma dielectric barrier discharge, with the aim of explaining the potential mechanisms through which it contributes to blood coagulation and enhances wound healing. Optical microscopy of cold atmospheric plasma (CAP) treated whole capillary blood showed an increase in red blood cell (RBC) size and the formation of rouleaux structures. The treatment of whole blood leads to hemolysis of RBCs and the release of intracellular protein content. We then treated purified hemoglobin protein at physiological concentrations, which led to the formation of aggregates that could be observed using ion mobility mass spectrometry (IM–MS), size exclusion chromatography, and optical microscopy. The aggregates formed fibril-like structures as observed using atomic force microscopy. The formation of hemoglobin aggregates is hypothesized to be the result of new intermolecular interactions formed following the CAP-mediated protein oxidation. We studied the changes to hemoglobin structure after treatment with a CAP using high-resolution MS and found that the hemoglobin subunits are oxidized with the addition of at least 4 oxygen atoms each. The intact tetrameric hemoglobin structure remains unchanged; however, the monomeric and dimeric proteins adopt a more compact structure, as observed by IM–MS. We propose that CAP treatment of fresh blood leads to hemolysis, and that the extracellular protein, primarily hemoglobin, is oxidized leading to the formation of aggregates.
  • Excited-State N Atoms Transform Aromatic Hydrocarbons into N-Heterocycles in Low-Temperature Plasmas
    Item type: Journal Article
    Begley, Alina; Shuman, Nicholas S.; Long, Bryan A.; et al. (2022)
    The Journal of Physical Chemistry A
    The direct formation of N-heterocycles from aromatic hydrocarbons has been observed in nitrogen-based low-temperature plasmas; the mechanism of this unusual nitrogen-fixation reaction is the topic of this paper. We used homologous aromatic compounds to study their reaction with reactive nitrogen species (RNS) in a dielectric barrier discharge ionization (DBDI) source. Toluene (C7H8) served as a model compound to study the reaction in detail, which leads to the formation of two major products at “high” plasma voltage: a nitrogen-replacement product yielding protonated methylpyridine (C6H8N+) and a protonated nitrogen-addition (C7H8N+) product. We complemented those studies by a series of experiments probing the potential mechanism. Using a series of selected-ion flow tube experiments, we found that N+, N2+, and N4+ react with toluene to form a small abundance of the N-addition product, while N(4S) reacted with toluene cations to form a fragment ion. We created a model for the RNS in the plasma using variable electron and neutral density attachment mass spectrometry in a flowing afterglow Langmuir probe apparatus. These experiments suggested that excited-state nitrogen atoms could be responsible for the N-replacement product. Density functional theory calculations confirmed that the reaction of excited-state nitrogen N(2P) and N(2D) with toluene ions can directly form protonated methylpyridine, ejecting a carbon atom from the aromatic ring. N(2P) is responsible for this reaction in our DBDI source as it has a sufficient lifetime in the plasma and was detected by optical emission spectroscopy measurements, showing an increasing intensity of N(2P) with increasing voltage.
  • Radical-Induced Selective C―C Bond Activation at the Air-Solid Interface
    Item type: Journal Article
    Liu, Qinlei; Begley, Alina; Abbott, Daniel F.; et al. (2025)
    Small
    Radicals are of great interest to trigger reactions in synthetic chemistry due to their high efficiency and unique reactivity, but their uncontrollable nature poses challenges in achieving selectivity. This study explores the influence of a surface/interface on radical reactions, leveraging a low-temperature plasma ionization source for radical generation. Combining insights from tip-enhanced Raman spectroscopy, mass spectrometry, and X-ray photoelectron spectroscopy, the selectivity of radical reactions of a model organic compound, biphenylthiol is investigated, under both homogeneous and heterogeneous conditions. The metal surface, acting as a template with interfacial water, is found to significantly modify the radical reaction pathway. The surface-immobilized BPT exhibited selective radical reaction products, forming 4-mercaptophenol molecules on Au(111) via the cleavage of C & horbar;C bonds. Such a high selectivity of radical reactions is unique and only achieved at the air/solid interface as compared to reactions in the gas, liquid, and solid phases. The present work highlights the potential of surfaces and interfaces in tailoring radical reaction pathways with high selectivity.
Publications 1 - 10 of 10