Jesse Lee Beauchamp

This study demonstrates a unique interface-specific SN2 reaction of the gemini surfactant decamethonium bromide at the air–water boundary. Using electrospray and field-induced droplet ionization mass spectrometry combined with DFT and COSMO-RS modeling, we show that interfacial charge alignment induces combination of two diammonium ions via water to yield an ether dimer. The reaction is absent in bulk solution and is strongly enhanced at the interface due to stabilization of a bent, Br–-pinned conformer. Computational results confirm reduced activation barriers and amphiphilic orientation driving interfacial reactivity, offering insight into charge-directed chemistry at liquid interfaces and new routes for controlled synthesis.

We have studied the interfacial properties of Zn²⁺ vs selected transition metal cations such as Fe²⁺, Cu²⁺, and Cr³⁺ in a water-ethanol mixture using field-induced droplet ionization. This was in particular inspired by the specific surface activity of Zn²⁺ that has been observed on several occasions and a desire to clarify the root cause for this behavior. We have found that Zn²⁺, due to its unique electronic configuration and atomic size, is the only ion of those under study that gives rise to specific speciation at the air-liquid interface with three ethanol molecules attached to the central atom for optimal polarity.

The oxidation of antioxidants by oxidizers imposes great challenges to both living organisms and the food industry. Here we show that the host–guest complexation of the carefully designed, positively charged, amphiphilic guanidinocalix[5]arene pentadodecyl ether (GC5A‐12C) and negatively charged oleic acid (OA), a well‐known cell membrane antioxidant, prevents the oxidation of the complex monolayers at the air–water interface from two potent oxidizers hydroxyl radicals (OH) and singlet delta oxygen (SDO). OH is generated from the gas phase and attacks from the top of the monolayer, while SDO is generated inside the monolayer and attacks amphiphiles from a lateral direction. Field‐induced droplet ionization mass spectrometry results have demonstrated that the host–guest complexation achieves steric shielding and prevents both types of oxidation as a result of the tight and “sleeved in” physical arrangement, rather than the chemical reactivity, of the complexes.

The oxidation of antioxidants by oxidizers imposes great challenges to both living organisms and the food industry. Here we show that the host–guest complexation of the carefully designed, positively charged, amphiphilic guanidinocalix[5]arene pentadodecyl ether (GC5A‐12C) and negatively charged oleic acid (OA), a well‐known cell membrane antioxidant, prevents the oxidation of the complex monolayers at the air–water interface from two potent oxidizers hydroxyl radicals (OH) and singlet delta oxygen (SDO). OH is generated from the gas phase and attacks from the top of the monolayer, while SDO is generated inside the monolayer and attacks amphiphiles from a lateral direction. Field‐induced droplet ionization mass spectrometry results have demonstrated that the host–guest complexation achieves steric shielding and prevents both types of oxidation as a result of the tight and “sleeved in” physical arrangement, rather than the chemical reactivity, of the complexes.

By combing the merits of solid supports and free radical activated glycan sequencing (FRAGS) reagents, we develop a multi-functional solid-supported free radical probe (SS-FRAGS), which enables glycan enrichment and characterization. SS-FRAGS comprises a solid support, free radical precursor, disulfide bond, pyridyl, and hydrazine moieties. Thio-activated resin and magnetic nanoparticles (MNPs) are chosen as the solid support to selectively capture free glycans via the hydrazine moiety, allowing for their enrichment and isolation. The disulfide bond acts as a temporary covalent linkage between the solid support and the captured glycan, allowing the release of glycans via the cleavage of the disulfide bond by dithiothreitol. The basic pyridyl functional group provides a site for the formation of a fixed charge, enabling detection by mass spectrometry and avoiding glycan rearrangement during collisional activation. The free radical precursor generates a nascent free radical upon collisional activation and thus simultaneously induces systematic and predictable fragmentation for glycan structure elucidation. A radical-driven glycan deconstruction diagram (R-DECON) is developed to visually summarize the MS2 results and thus allow for the assembly of the glycan skeleton, making the differentiation of isobaric glycan isomers unambiguous. For application to a real-world sample, we demonstrate the efficacy of the SS-FRAGS by analyzing glycan structures enzymatically cleaved from RNase-B.

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.

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.

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 efforts have 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 li-pids/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.

Significance: Comprising 30 mol % of the lipids in cell membranes, cholesterol plays vital biophysical roles in monolayer and bilayer membranes. It increases the lipid-packing density and maintains high membrane fluidity. Most studies of cholesterol in membranes focus on its effects on membrane structure and physical properties, with only minimum concern for possible biochemical consequences that might accompany these changes. In this study, field-induced droplet ionization mass spectrometry is employed to directly measure the chemical degradation of monolayer phospholipids caused by potent reagents OH and HCl at the air–water interface. When added to the lipid layer, cholesterol serves a nonsacrificial chemoprotective function, inhibiting the substantial degradation of both 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) that occurs in the absence of cholesterol.