Field-induced Droplet Ionization Mass Spectrometry Research Articles

Tools to Investigate Structure at Hydrocarbon–Air Interfaces: Field-Induced Droplet Ionization Mass Spectrometry and Sum-Frequency Generation with Pulsed Lasers

Tools to Investigate Structure at Hydrocarbon–Air Interfaces: Field-Induced Droplet Ionization Mass Spectrometry and Sum-Frequency Generation with Pulsed Lasers

Fast Hydroxyl Radical Generation at the Air-Water Interface of Aerosols Mediated by Water-Soluble PM2.5 under Ultraviolet A Radiation.

Due to the adverse health effects and the role in the formation of secondary organic aerosols, hydroxyl radical (OH) generation by atmospheric fine particulate matter (PM) has been of particular research interest in both bulk solutions and the gas phase. However, OH generation by PM at the air-water interface of atmospheric water droplets, a unique environment where reactions can be accelerated by orders of magnitude, has long been overlooked. Using the field-induced droplet ionization mass spectrometry methodology that selectively samples molecules at the air-water interface, here, we show significant oxidation of amphiphilic lipids and isoprene mediated by water-soluble PM2.5 at the air-water interface under ultraviolet A irradiation, with the OH generation rate estimated to be 1.5 × 1016 molecule·s-1·m-2. Atomistic molecular dynamics simulations support the counter-intuitive affinity for the air-water interface of isoprene. We opine that it is the carboxylic chelators of the surface-active molecules in PM that enrich photocatalytic metals such as iron at the air-water interface and greatly enhance the OH generation therein. This work provides a potential new heterogeneous OH generation channel in the atmosphere.

Mass Spectrometry and Cryogenic Electron Microscopy Illuminate Molecular-Level Mechanisms of the Oxidative and Structural Damage to Lipid Membranes by Radical-Bearing Graphene Oxide.

Biomedical applications of graphene in tumor and bacterial treatment have become cutting-edge fields due to its unique physical and chemical properties. However, a mechanistic understanding of the interactions and reactions between graphene-based material and biological systems such as lipid membranes remains elusive, especially at the molecular level. By using the unique field-induced droplet ionization mass spectrometry and cryogenic electron microscopy methodologies, we reveal the oxidation products of monolayer lipid membranes at the air-water interface and the change in the morphology of bilayer lipid membranes in an aqueous solution caused by the incorporation of graphene oxide bearing π-conjugated carbon radicals [hydrated graphene oxide (hGO)]. We discovered that hGO is an efficient source of hydroxyl radicals and that it is not only the incorporation of the hGO sheets but also the irregular packing of the lipid oxides from the hydroxyl radical oxidation that causes the structural distortions of the liposomes.

Stiffening Effect of Ceramide on Lipid Membranes Provides Non-Sacrificial Protection against Potent Chemical Damage.

Ceramide is a sphingolipid that constitutes only a small fraction of membrane biomolecules but plays a central role in regulating many biological processes. The ceramide level in cell membranes can drastically increase in response to external damage, which has been hypothesized to involve ceramide's biophysical role that increases the membrane packing density and lowers the membrane permeability. However, direct observation of the consequent influence on membrane chemistry resulting from these ceramide-induced physical properties has been absent. Using our unique field-induced droplet ionization mass spectrometry technique combined with molecular dynamics simulations, here we report that the addition of ceramide to POPC monolayer membranes at the air-water interface greatly reduces the chemical damage from potent chemicals, •OH radicals, and HCl vapor, by stiffening the membrane packing and lowering the permeability. These results shed new light on the underlying chemoprotective role of ceramide in lipid membranes, which might serve as a previously unknown protection mechanism in response to external stimuli that cause cell stress or death.

A Targeted Photosensitizer Mediated by Visible Light for Efficient Therapy of Bacterial Keratitis.

Bacterial keratitis is a serious bacterial infection of the cornea that can cause sight loss in severe cases because of the sharp decline of efficacious antibiotics. Herein, a targeted photosensitizer based on BODIPY severing as a photobactericidal agent was developed for treating bacterial keratitis. The water solubility of the material was as high as 10 mg/mL, which was attributable to the introduction of pathogen-targeting galactose and fucose. The photosensitizer was able to preferentially bind Pseudomonas aeruginosa instead of mammalian cells and trigger the aggregation of bacteria, which ultimately facilitated effective pathogen ablation upon the generation of reactive oxygen species (ROS) via laser irradiation. Photoexcited targeted photosensitizers can promote wound healing by eradicating P. aeruginosa in rat eyes and reducing the inflammatory response, thus exhibiting the significant therapeutic effect on bacterial keratitis. We also performed molecular level mechanistic studies using the unique field-induced droplet ionization mass spectrometry methodology and confirmed that the generated ROS were mainly singlet oxygen that caused lipid peroxidation (Type II mechanism). We anticipate that the targeted photosensitizer will have great potential in the application of clinical photodynamic therapy to ocular infection.

Unravelling Melatonin's Varied Antioxidizing Protection of Membrane Lipids Determined by its Spatial Distribution.

The antioxidizing capability of membrane antioxidants is strongly affected by the submolecular regions of the membrane that they locate. However, the concurrent determination of their location in the membranes and the consequent antioxidizing effect remains difficult. Using our field-induced droplet ionization mass spectrometry methodology, here we show the rapid determination of the antioxidation effect and the spatial distribution of melatonin in POPC membranes. Melatonin effectively protects the membrane lipids against hydroxyl radicals originating from the Fenton reactions in the water phase but cannot protect the lipids against singlet oxygen generated by a lipophilic photosensitizer in the lipid tail region (oil phase). These varied antioxidizing behaviors indicate that melatonin dwells at the headgroup subregion of the membranes. We anticipate that the methodology in this study can be widely utilized in the screening of antioxidants' spatial distribution and antioxidizing efficiency, and eventually in designing novel antioxidants that could deliver specific functions.

Investigation of the Acid-Mediated Photosensitized Reactions of Amphiphilic α-Keto Acids at the Air–Water Interface Using Field-Induced Droplet Ionization Mass Spectrometry

The photochemistry of α-keto acids has been of great interest due to its implications in atmospheric and prebiotic chemistries. α-Keto acids with long alkyl chains are amphiphilic in nature, and they tend to partition at the air-water interface of atmospheric water droplets and add to the complexity of the chemistries therein. The air-water interface is a unique environment that plays a vital role in overall atmospheric processes. However, existing studies mostly focus on the photochemistry of α-keto acids in the bulk solution and neglect the reactions that occur at the interface. In this study, using the field-induced droplet ionization mass spectrometry methodology that is capable of selectively sampling amphiphilic molecules that reside at the air-water interface, we show that the acid-mediated photochemistry of 2-oxooctanoic acid and 2-oxoheptoic acid is highly different from those of previously reported reactions in the bulk and contributes to the formation of humic-like substances (HULIS). This work emphasizes the uniqueness of the photochemistry at the air-water interface. We anticipate that studies of atmosphere-relevant photochemistry at the air-water interface will be an avenue rich with opportunities.

Free-Radical-Initiated Phospholipid Oxidations at the Air–Water Interface: The Oxidation of Unsaturated and Saturated Fatty Acid Chains

Lipid oxidations initiated by free radicals are usually considered to undergo peroxidation, a chain process starting with hydrogen abstraction by an initiator, followed by O2 uptake. While this peroxidation mechanism is widely accepted and sometimes taken for granted, here we provide evidence of the oxidation of both of the unsaturated and saturated fatty acid chains in phospholipids initiated by photoinitiator 2,4,6-trimethylbenzoyl diphenylphosphine oxide (TMDPO) at the air-water interface, and no peroxidation products are observed in these reactions. A unique field-induced droplet ionization mass spectrometry (FIDI-MS) methodology which is capable of the selective online sampling of monolayers of molecules that reside at the air-water interface is employed to detect the products. We have shown that the double bonds on the oleyl chains of the lipids are first oxidized into epoxides, after which other saturated carbon atoms are oxidized into carbonyl groups. We anticipate that this work will draw more attention to the complexity of the lipid oxidation chemistry initiated by free radicals.

Mass spectrometry at the air-water interface

In this Young Scholar Perspective, the history, applications, and outlook of a unique methodology, field-induced droplet ionization mass spectrometry (FIDI-MS) are discussed. FIDI-MS is capable of selective in-situ sampling of molecules that reside at the air-water interface of droplets right after chemical reactions without any sample handling or transfer, and suffers minimal influence from the bulk of the solution. Its applications in studying the air-water interface chemistry in the contexts of molecular biology, atmospheric chemistry, molecular recognition, and the insights it has brought to these fields are introduced in this Perspective. Looking to the future, we anticipate that further development and applications of FIDI-MS in various fields will be an avenue rich with opportunities.

Probe‐Free Direct Identification of Type I and Type II Photosensitized Oxidation Using Field‐Induced Droplet Ionization Mass Spectrometry

AbstractWhile Type I and Type II photosensitizers are often carefully tailored to achieve their respective advantages in treating different cancers, the identifications of the Type I and II mechanisms as such, the key reaction intermediates, and the consequent oxidation products of the substrates have never been easy. Using our unique home‐built field‐induced droplet ionization mass spectrometry (FIDI‐MS) method that selectively samples molecules at the air–water interface, here we show the facile determination of both Type I and II mechanisms of a poster‐child photosensitizer, temoporfin, without the addition of any probes. The unstable doublet radical resulting from the hydrogen abstraction by the triplet temoporfin through the Type I mechanism is captured, manifesting the in situ advantage of FIDI‐MS. We anticipate that the method developed in this study can be widely utilized in the future designs of novel photosensitizers and the screening of their photosensitization mechanisms.

Probe-Free Direct Identification of Type I and Type II Photosensitized Oxidation Using Field-Induced Droplet Ionization Mass Spectrometry.

While Type I and Type II photosensitizers are often carefully tailored to achieve their respective advantages in treating different cancers, the identifications of the Type I and II mechanisms as such, the key reaction intermediates, and the consequent oxidation products of the substrates have never been easy. Using our unique home-built field-induced droplet ionization mass spectrometry (FIDI-MS) method that selectively samples molecules at the air-water interface, here we show the facile determination of both Type I and II mechanisms of a poster-child photosensitizer, temoporfin, without the addition of any probes. The unstable doublet radical resulting from the hydrogen abstraction by the triplet temoporfin through the Type I mechanism is captured, manifesting the in situ advantage of FIDI-MS. We anticipate that the method developed in this study can be widely utilized in the future designs of novel photosensitizers and the screening of their photosensitization mechanisms.

Beyond lipid peroxidation: Distinct mechanisms observed for POPC and POPG oxidation initiated by UV-enhanced Fenton reactions at the air-water interface.

Fenton or Fenton-like reactions are ubiquitous in nature, and the hydroxyl radicals (·OH) generated in these reactions are accountable for a plethora of oxidation processes both in the environment and in vivo. Among these oxidation reactions, lipid oxidation initiated by ·OH radicals has long been oversimplified as a peroxidation mechanism, but in reality, it is a highly complicated process that can result in a large variety of products. Using the unique field-induced droplet ionization mass spectrometry (FIDI-MS) methodology that is capable of selective sampling of amphiphilic molecules that reside at the air-water interface, here, we show distinct mechanisms from the ultraviolet (UV)-enhanced Fenton oxidations of two phospholipids, POPC and POPG, even though these two lipids possess the same functional groups that are vulnerable to ·OH attack. We postulate that it is the different packing densities that determine the permeability of ambient NO molecules into the monolayers, resulting in highly distinct reaction pathways and products. We anticipate that this work will be a wake-up call that the lipid peroxidation mechanism is sometimes taken for granted and that lipid oxidation can be subtly affected by various factors that deserves deeper investigations.

Mass Spectrometric Study of Acoustically Levitated Droplets Illuminates Molecular-Level Mechanism of Photodynamic Therapy for Cancer involving Lipid Oxidation.

Even though the general mechanism of photodynamic cancer therapy is known, the details and consequences of the reactions between the photosensitizer-generated singlet oxygen and substrate molecules remain elusive at the molecular level. Using temoporfin as the photosensitizer, here we combine field-induced droplet ionization mass spectrometry and acoustic levitation techniques to study the "wall-less" oxidation reactions of 18:1 cardiolipin and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) mediated by singlet oxygen at the air-water interface of levitated water droplets. For both cardiolipin and POPG, every unsaturated oleyl chain is oxidized to an allyl hydroperoxide, which surprisingly is immune to further oxidation. This is attributed to the increased hydrophilicity of the oxidized chain, which attracts it toward the water phase, thereby increasing membrane permeability and eventually triggering cell death.

Subtle Changes in Lipid Environment Have Profound Effects on Membrane Oxidation Chemistry.

Nature carefully designs the components of amphiphile-composed monolayer and bilayer membranes to deliver specific functions. The compositions of these interfacial layered structures are so delicate that minute modifications can result in huge changes in function. Great effort has been expended to understand membrane physical properties, with only minimum attention given to associated chemical properties. Here we report the first examples of the delicate chemistry associated with membrane amphiphilic components by studying OH-mediated oxidation of six different unsaturated lipids/surfactants and their mixtures at the air-water interface using field-induced droplet ionization mass spectrometry (FIDI-MS). When the packing is loose or perturbed to be loose by other components or prior chemical modification, the double bond is oxidized without cleavage by adding oxygen functionality. In contrast, compact packing results in double bond cleavage through a Criegee intermediate mechanism. We postulate that constrained environments imposed by lipid packing limit the conformations of the reaction intermediates, controlling reaction pathways.

Probing the OH Oxidation of Pinonic Acid at the Air-Water Interface Using Field-Induced Droplet Ionization Mass Spectrometry (FIDI-MS).

Gas and aqueous phases are essential media for atmospheric chemistry and aerosol formation. Numerous studies have focused on aqueous-phase reactions as well as coupled gas/aqueous-phase mass transport and reaction. Few studies have directly addressed processes occurring at the air-water interface, especially involving surface-active compounds. We report here the application of field-induced droplet ionization mass spectrometry (FIDI-MS) to chemical reactions occurring at the atmospheric air-water interface. We determine the air-water interfacial OH radical reaction rate constants for sodium dodecyl sulfate (SDS), a common surfactant, and pinonic acid (PA), a surface-active species and proxy for biogenic atmospheric oxidation products, as 2.87 × 10-8 and 9.38 × 10-8 cm2 molec-1 s-1, respectively. In support of the experimental data, a comprehensive gas-surface-aqueous multiphase transport and reaction model of general applicability to atmospheric interfacial processes is developed. Through application of the model, PA is shown to be oxidized exclusively at the air-water interface of droplets with a diameter of 5 μm under typical ambient OH levels. In the absence of interfacial reaction, aqueous- rather than gas-phase oxidation is the major PA sink. We demonstrate the critical importance of air-water interfacial chemistry in determining the fate of surface-active species.

Time resolved study of hydroxyl radical oxidation of oleic acid at the air-water interface

The ubiquity of oleic acid (OA) renders it a poster child for laboratory investigations of environmental oxidation chemistry. In the current study, mechanistic details of the oxidation of OA by hydroxyl radicals at the air-water interface are investigated using field-induced droplet ionization mass spectrometry (FIDI-MS). Products from OH oxidation of both unsaturated and saturated carbon atoms are identified, and mechanisms for both types of oxidation processes are proposed. Uptake of oxygen in the interfacial layer increases linearly with time, consistent with Langmuir-Hinshelwood reaction kinetics. These results provide fundamental knowledge relating to OH initiated degradation of fatty acids in atmospheric aerosols.

Real-Time Studies of Iron Oxalate-Mediated Oxidation of Glycolaldehyde as a Model for Photochemical Aging of Aqueous Tropospheric Aerosols.

The complexation of iron(III) with oxalic acid in aqueous solution yields a strongly absorbing chromophore that undergoes efficient photodissociation to give iron(II) and the carbon dioxide anion radical. Importantly, iron(III) oxalate complexes absorb near-UV radiation (λ > 350 nm), providing a potentially powerful source of oxidants in aqueous tropospheric chemistry. Although this photochemical system has been studied extensively, the mechanistic details associated with its role in the oxidation of dissolved organic matter within aqueous aerosol remain largely unknown. This study utilizes glycolaldehyde as a model organic species to examine the oxidation pathways and evolution of organic aerosol initiated by the photodissociation of aqueous iron(III) oxalate complexes. Hanging droplets (radius 1 mm) containing iron(III), oxalic acid, glycolaldehyde, and ammonium sulfate (pH ∼3) are exposed to irradiation at 365 nm and sampled at discrete time points utilizing field-induced droplet ionization mass spectrometry (FIDI-MS). Glycolaldehyde is found to undergo rapid oxidation to form glyoxal, glycolic acid, and glyoxylic acid, but the formation of high molecular weight oligomers is not observed. For comparison, particle-phase experiments conducted in a laboratory chamber explore the reactive uptake of gas-phase glycolaldehyde onto aqueous seed aerosol containing iron and oxalic acid. The presence of iron oxalate in seed aerosol is found to inhibit aerosol growth. These results suggest that photodissociation of iron(III) oxalate can lead to the formation of volatile oxidation products in tropospheric aqueous aerosols.

Studying Interfacial Reactions of Cholesterol Sulfate in an Unsaturated Phosphatidylglycerol Layer with Ozone Using Field Induced Droplet Ionization Mass Spectrometry

Field-induced droplet ionization (FIDI) is a recently developed ionization technique that can transfer ions from the surface of microliter droplets to the gas phase intact. The air-liquid interfacial reactions of cholesterol sulfate (CholSO(4)) in a 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) surfactant layer with ozone (O(3)) are investigated using field-induced droplet ionization mass spectrometry (FIDI-MS). Time-resolved studies of interfacial ozonolysis of CholSO(4) reveal that water plays an important role in forming oxygenated products. An epoxide derivative is observed as a major product of CholSO(4) oxidation in the FIDI-MS spectrum after exposure of the droplet to O(3) for 5 s. The abundance of the epoxide product then decreases with continued O(3) exposure as the finite number of water molecules at the air-liquid interface becomes exhausted. Competitive oxidation of CholSO(4) and POPG is observed when they are present together in a lipid surfactant layer at the air-liquid interface. Competitive reactions of CholSO(4) and POPG with O(3) suggest that CholSO(4) is present with POPG as a well-mixed interfacial layer. Compared with CholSO(4) and POPG alone, the overall ozonolysis rates of both CholSO(4) and POPG are reduced in a mixed layer, suggesting the double bonds of both molecules are shielded by additional hydrocarbons from one another. Molecular dynamics simulations of a monolayer comprising POPG and CholSO(4) correlate well with experimental observations and provide a detailed picture of the interactions between CholSO(4), lipids, and water molecules in the interfacial region.

Time Resolved Studies of Interfacial Reactions of Ozone with Pulmonary Phospholipid Surfactants Using Field Induced Droplet Ionization Mass Spectrometry

Field induced droplet ionization mass spectrometry (FIDI-MS) comprises a soft ionization method to sample ions from the surface of microliter droplets. A pulsed electric field stretches neutral droplets until they develop dual Taylor cones, emitting streams of positively and negatively charged submicrometer droplets in opposite directions, with the desired polarity being directed into a mass spectrometer for analysis. This methodology is employed to study the heterogeneous ozonolysis of 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) at the air-liquid interface in negative ion mode using FIDI mass spectrometry. Our results demonstrate unique characteristics of the heterogeneous reactions at the air-liquid interface. We observe the hydroxyhydroperoxide and the secondary ozonide as major products of POPG ozonolysis in the FIDI-MS spectra. These products are metastable and difficult to observe in the bulk phase, using standard electrospray ionization (ESI) for mass spectrometric analysis. We also present studies of the heterogeneous ozonolysis of a mixture of saturated and unsaturated phospholipids at the air-liquid interface. A mixture of the saturated phospholipid 1,2-dipalmitoyl-sn-phosphatidylglycerol (DPPG) and unsaturated POPG is investigated in negative ion mode using FIDI-MS while a mixture of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and 1-stearoyl-2-oleoyl-sn-phosphatidylcholine (SOPC) surfactant is studied in positive ion mode. In both cases FIDI-MS shows the saturated and unsaturated pulmonary surfactants form a mixed interfacial layer. Only the unsaturated phospholipid reacts with ozone, forming products that are more hydrophilic than the saturated phospholipid. With extensive ozonolysis only the saturated phospholipid remains at the droplet surface. Combining these experimental observations with the results of computational analysis provides an improved understanding of the interfacial structure and chemistry of a surfactant layer system when subject to oxidative stress.

Evaporation and Discharge Dynamics of Highly Charged Multicomponent Droplets Generated by Electrospray Ionization

We investigate the Rayleigh discharge and evaporation dynamics of highly charged two-component droplets consisting principally of methanol with 2-methoxyethanol, tert-butanol, or m-nitrobenzyl alcohol. A phase Doppler anemometer (PDA) characterizes droplets generated by electrospray ionization (ESI) according to size, velocity, and charge as they move through a uniform electric field within an ion mobility spectrometer (IMS). Repeated field reversals result in droplet "ping-pong" through the PDA. This generates individual droplet histories of solvent evaporation behavior and the dynamics of charge loss to progeny droplets during Rayleigh discharge events. On average, methanol droplets discharge at 127% their Rayleigh limit of charge, q(R), and release 25% of the net charge. Charge loss from methanol/2-methoxyethanol droplets behaves similarly to pure 2-methoxyethanol droplets which release approximately 28% of their net charge. Binary methanol droplets containing up to 50% tert-butanol discharge at a lower percent q(R) than pure methanol and release a greater fraction of their net charge. Mixed 99% methanol/1% m-nitrobenzyl alcohol droplets possess discharge characteristics similar to those of methanol. However, droplets of methanol containing 2% m-nitrobenzyl evaporate down to a fixed size and charge that remains constant with no observable discharges. Quasi-steady-state evaporation models accurately describe observed evaporation phenomena in which methanol/tert-butanol droplets evaporate at a rate similar to that of pure methanol and methanol/2-methoxyethanol droplets evaporate at a rate similar to that of 2-methoxyethanol. We compare these results to previous Rayleigh discharge experiments and discuss the implications for binary solvents in electrospray mass spectrometry (ESI-MS) and field-induced droplet ionization mass spectrometry (FIDI-MS).