The Spontaneous Electron-Mediated Redox Processes on Sprayed Water Microdroplets.

Water is considered as an inert environment for the dispersion of many chemical systems. However, by simply spraying bulk water into microsized droplets, the water microdroplets have been shown to possess a large plethora of unique properties, including the ability to accelerate chemical reactions by several orders of magnitude compared to the same reactions in bulk water, and/or to trigger spontaneous reactions that cannot occur in bulk water. A high electric field (∼109 V/m) at the air-water interface of microdroplets has been postulated to be the probable cause of the unique chemistries. This high field can even oxidize electrons out of hydroxide ions or other closed-shell molecules dissolved in water, forming radicals and electrons. Subsequently, the electrons can trigger further reduction processes. In this Perspective, by showing a large number of such electron-mediated redox reactions, and by studying the kinetics of these reactions, we opine that the redox reactions on sprayed water microdroplets are essentially processes using electrons as the charge carriers. The potential impacts of the redox capability of microdroplets are also discussed in a larger context of synthetic chemistry and atmospheric chemistry.

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.

Fast Sulfate Formation Initiated by the Spin-Forbidden Excitation of SO2 at the Air-Water Interface.

The multiphase oxidation of SO2 to sulfate in aerosol particles is a key process in atmospheric chemistry. However, there is a large gap between the observed and simulated sulfate concentrations during severe haze events. To fill in the gaps in understanding SO2 oxidation chemistry, a combination of experiments and theoretical calculations provided evidence for the direct, spin-forbidden excitation of SO2 to its triplet states using UVA photons at an air-water interface, followed by reactions with water and O2 that facilitate the rapid formation of sulfate. The estimated reaction energy for the whole process, 3SO2 + H2O + 1/2O2 → HSO4- + H+ (298 K, 1 M), was ΔGr = -107.8 kcal·mol-1. Moreover, calculations revealed that this was a multistep reaction involving submerged, small energy barriers (∼10 kcal·mol-1). These results indicate that photochemical oxidation of SO2 at the air-water interface with solar actinic light may be an important unaccounted source of sulfate aerosols under polluted haze conditions.

Certification of Genuine Multipartite Entanglement with General and Robust Device-Independent Witnesses.

Genuine multipartite entanglement represents the strongest type of entanglement, which is an essential resource for quantum information processing. Standard methods to detect genuine multipartite entanglement, e.g., entanglement witnesses, state tomography, or quantum state verification, require full knowledge of the Hilbert space dimension and precise calibration of measurement devices, which are usually difficult to acquire in an experiment. The most radical way to overcome these problems is to detect entanglement solely based on the Bell-like correlations of measurement outcomes collected in the experiment, namely, device independently. However, it is difficult to certify genuine entanglement of practical multipartite states in this way, and even more difficult to quantify it, due to the difficulty in identifying optimal multipartite Bell inequalities and protocols tolerant to state impurity. In this Letter, we explore a general and robust device-independent method that can be applied to various realistic multipartite quantum states in arbitrary finite dimension, while merely relying on bipartite Bell inequalities. Our method allows us both to certify the presence of genuine multipartite entanglement and to quantify it. Several important classes of entangled states are tested with this method, leading to the detection of genuinely entangled states. We also certify genuine multipartite entanglement in weakly entangled Greenberger-Horne-Zeilinger states, showing that the method applies equally well to less standard states.

High Electric Field on Water Microdroplets Catalyzes Spontaneous and Ultrafast Oxidative C-H/N-H Cross-Coupling.

Oxidative C-H/N-H cross-coupling has emerged as an atom-economical method for the construction of C-N bonds. Conventional oxidative C-H/N-H coupling requires at least one of the following: high temperatures, strong oxidizers, transition metal catalysts, organic solvents, light, and electrochemical cells. In this study, by merely spraying the water solutions of the substrates into microdroplets at room temperature, we show a series of oxidative C-H/N-H coupling products that are strikingly produced in a spontaneous and ultrafast manner. The reactions are accelerated by six orders of magnitude compared to the same reactions in the bulk. It has been previously proposed by fluorescence microscopy and theory that the spontaneously generated electric field at the microdroplets peripheries can be in the ∼109 V/m range. Based on mass spectrometric analysis of key radical intermediates, we opine that the ultrahigh electric field catalytically oxidizes the substrates by removing an electron, which further promotes C/N coupling. Taken together, we anticipate that microdroplet chemistry will be an avenue rich in green opportunities of constructing C-heteroatom bonds.

Sprayed water microdroplets containing dissolved pyridine spontaneously generate pyridyl anions.

The anion of pyridine, C5H5N−, has been thought to be short lived in the gas phase and was only previously observed indirectly. In the condensed phase, C5H5N− is known to be stabilized by solvation with other molecules. We provide in this study striking results for the formation of isolated C5H5N− from microdroplets of water containing dissolved pyridine observed in the negative ion mass spectrum. The gas-phase lifetime of C5H5N− is estimated to be at least 50 ms, which is much longer than previously thought. The generated C5H5N− captured CO2 molecules to form a stable (Py-CO2)− complex, further confirming the existence of C5H5N−. We propose that the high electric field at the air­water interface of a microdroplet helps OH− to transfer an electron to pyridine to form C5H5N− and the hydroxyl radical •OH. Oxidation products of the Py reacting with •OH are also observed in the mass spectrum recorded in positive mode, which further supports this mechanism. The present study pushes the limits of the reducing and oxidizing power of water microdroplets to a new level, emphasizing how different the behavior of microdroplets can be from bulk water. We also note that the easy formation of C5H5N− in water microdroplets presents a green chemistry way to synthesize value-added chemicals.

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.

Spontaneous Reduction-Induced Degradation of Viologen Compounds in Water Microdroplets and Its Inhibition by Host-Guest Complexation.

Water serves as an inert environment for the dispersion and application of many kinds of herbicides. Viologen compounds, a type of widely used but highly toxic herbicide, are stable in bulk water, whose half-life can be up to 23 weeks in natural water, imposing a severe health risk to mammals. In this study, we present the striking results of the spontaneous and ultrafast reduction-induced degradation of three viologen compounds in water microdroplets and provide the concentration, time, temperature dependence, mechanism, and scale-up of the reactions. We postulate that the electrons existing at the air-water interface of the microdroplets due to the unique redox potential therein initiate the reduction, from which further degradation occurs. The host-guest complexation between cucurbit[7]uril and viologens only slightly changes the redox potential of viologens in the bulk but completely inhibits the reactions in microdroplets, adding to the uniqueness of the redox potentials at the air-water interfaces of microdroplets. Taken together, microdroplets might have been functioning as naturally occurring ubiquitous tiny electrochemical cells for a plethora of unique redox reactions that were thought to be impossible in the bulk water.

Revisiting the Hitherto Elusive Cyclohexanehexone Molecule: Bulk Synthesis, Mass Spectrometry, and Theoretical Studies.

The cyclohexanehexone (C6O6) octahydrate molecule was claimed to be synthesized as early as 1862. However, the chemical in the 1862 study and the chemicals used in most of the existing studies and sold by most chemical vendors are actually dodecahydroxycyclohexane dihydrate (C6(OH)12·2H2O). Here we revisit our bulk synthesis method of C6O6 by the dehydration of the C6(OH)12·2H2O material, and report the mass spectrum of C6O6 that has been highly challenging to obtain owing to its high sensitivity toward ambient conditions. A new home-built electrospray ionization mass spectrometry setup in a glovebox is utilized to detect C6O6 in the form of C6O6H-. Tandem mass spectrometry MSn (n = 2-4) presents consecutive losses of CO molecules, further confirming the structure of C6O6. Theoretical calculations are performed to recover the chemical bonding of C6O6 and to rationalize the synthetic method. This work provides a benchmark understanding of the historically elusive C6O6.

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.

Improving the precision of optical metrology by detecting fewer photons with biased weak measurement.

In optical metrological protocols to measure physical quantities, it is, in principle, always beneficial to increase photon number n to improve measurement precision. However, practical constraints prevent the arbitrary increase of n due to the imperfections of a practical detector, especially when the detector response is dominated by the saturation effect. In this work, we show that a modified weak measurement protocol, namely, biased weak measurement significantly improves the precision of optical metrology in the presence of saturation effect. This method detects an ultra-small fraction of photons while maintains a considerable amount of metrological information. The biased pre-coupling leads to an additional reduction of photons in the post-selection and generates an extinction point in the spectrum distribution, which is extremely sensitive to the estimated parameter and difficult to be saturated. Therefore, the Fisher information can be persistently enhanced by increasing the photon number. In our magnetic-sensing experiment, biased weak measurement achieves precision approximately one order of magnitude better than those of previously used methods. The proposed method can be applied in various optical measurement schemes to remarkably mitigate the detector saturation effect with low-cost apparatuses.

Beating Standard Quantum Limit with Weak Measurement.

Weak measurements have been under intensive investigation in both experiment and theory. Numerous experiments have indicated that the amplified meter shift is produced by the post-selection, yielding an improved precision compared to conventional methods. However, this amplification effect comes at the cost of a reduced rate of acquiring data, which leads to an increasing uncertainty to determine the level of meter shift. From this point of view, a number of theoretical works have suggested that weak measurements cannot improve the precision, or even damage the metrology information due to the post-selection. In this review, we give a comprehensive analysis of the weak measurements to justify their positive effect on prompting measurement precision. As a further step, we introduce two modified weak measurement protocols to boost the precision beyond the standard quantum limit. Compared to previous works beating the standard quantum limit, these protocols are free of using entangled or squeezed states. The achieved precision outperforms that of the conventional method by two orders of magnitude and attains a practical Heisenberg scaling up to n=106 photons.

BMSC-derived exosomes ameliorate sulfur mustard-induced acute lung injury by regulating the GPRC5A-YAP axis.

Sulfur mustard (SM) is a highly toxic chemical warfare agent that causes acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). There are no effective therapeutic treatments or antidotes available currently to counteract its toxic effects. Our previous study shows that bone marrow-derived mesenchymal stromal cells (BMSCs) could exert therapeutic effects against SM-induced lung injury. In this study, we explored the therapeutic potential of BMSC-derived exosomes (BMSC-Exs) against ALI and the underlying mechanisms. ALI was induced in mice by injection of SM (30 mg/kg, sc) at their medial and dorsal surfaces. BMSC-Exs (20 µg/kg in 200 µL PBS, iv) were injected for a 5-day period after SM exposure. We showed that BMSC-Exs administration caused a protective effect against pulmonary edema. Using a lung epithelial cell barrier model, BMSC-Exs (10, 20, 40 µg) dose-dependently inhibited SM-induced cell apoptosis and promoted the recovery of epithelial barrier function by facilitating the expression and relocalization of junction proteins (E-cadherin, claudin-1, occludin, and ZO-1). We further demonstrated that BMSC-Exs protected against apoptosis and promoted the restoration of barrier function against SM through upregulating G protein-coupled receptor family C group 5 type A (GPRC5A), a retinoic acid target gene predominately expressed in the epithelial cells of the lung. Knockdown of GPRC5A reduced the antiapoptotic and barrier regeneration abilities of BMSC-Exs and diminished their therapeutic effects in vitro and in vivo. BMSC-Exs-caused upregulation of GPRC5A promoted the expression of Bcl-2 and junction proteins via regulating the YAP pathway. In summary, BMSC-Exs treatment exerts protective effects against SM-induced ALI by promoting alveolar epithelial barrier repair and may be an alternative approach to stem cell-based therapy.

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.

ThH5 : An Actinide-Containing Superhalogen Molecule.

Thorium and its compounds have been widely investigated as important nuclear materials. Previous research focused on the potential use of thorium hydrides, such as ThH2 , ThH4 , and Th4 H15 , as nuclear fuels. Here, we report studies of the anion, ThH5- , by anion photoelectron spectroscopy and computations. The resulting experimental and theoretical vertical detachment energies (VDE) for ThH5- are 4.09 eV and 4.11 eV, respectively. These values and the agreement between theory and experiment facilitated the characterization of the structure of the ThH5- anion and showed its neutral counterpart, ThH5 to be a superhalogen. ThH5- , which exhibits a C4v structure with five Th-H single bonds, possesses the largest known H/M ratio among the actinide elements, M. The adaptive natural density partitioning (AdNDP) method was used to further analyze the chemical bonding of ThH5- and to confirm the existence of five Th-H single bonds in the ThH5- molecular anion.

Bleomycin: A novel osteogenesis inhibitor of dental follicle cells via a TGF-ß1/SMAD7/RUNX2 pathway.

BACKGROUND AND PURPOSE: Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown. EXPERIMENTAL APPROACH: Human dental follicle cells (hDFCs) were treated by bleomycin or exogenous TGF-ß1 or transfected by plasmids loading SMAD7 or shRNA targeting SMAD7, followed by osteogenesis induction assay and signalling analysis. Human fresh DF tissues and Wistar rats were used to further confirm bleomycin function. KEY RESULTS: Bleomycin decreased expression of RUNX2 and osteogenic genes in hDFCs, reducing osteogenic capacity. TGF-ß1 expression was up-regulated in bleomycin-treated hDFCs. The effects of exogenous TGF-ß1 were similar to those of bleomycin in hDFCs. Additionally, compared to SMAD2/3, SMAD7 expression increased more in bleomycin- or TGF-ß1-treated hDFCs. Overexpression of SMAD7 likewise significantly decreased RUNX2 expression and osteogenic capacity of hDFCs. Knockdown of SMAD7 markedly attenuated the inhibitory effects of bleomycin and TGF-ß1 on osteogenic capacity and RUNX2 expression of hDFCs. Most importantly, changes in TGF-ß1, SMAD7, and RUNX2 expressions were similar in the DF of rats and humans treated with bleomycin. CONCLUSION AND IMPLICATIONS: SMAD7 was a negative regulator of osteogenic differentiation in DFCs through suppressing RUNX2 expression. Bleomycin or TGF-ß1 inhibited osteogenic differentiation of DFCs via a TGF-ß1/SMAD7/RUNX2 pathway. Our findings might be beneficial for enhancing the osteogenic activity of DFCs or inhibiting the eruption of undesirable teeth.

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.

Magic Clusters PtMg2,3 H5 - Facilitated by Local σ-Aromaticity.

The concept of local aromaticity has been successfully utilized in understanding the stability of certain atomic clusters. However, all the skeleton atoms in these clusters are covered by at least one local aromatic feature, collectively making the multiple local aromaticities coexist globally. Herein we show the robustness of local aromaticity as a tool for the discovery of novel magic clusters: not all of the skeleton atoms need to be covered by an aromatic feature to make the cluster magic. In this study, the PtMg2,3 H5 - cluster anions are generated by a unique high-current pulsed discharge ion source and found to be magic numbers using mass spectrometry. Photoelectron spectroscopy and calculations confirm that only the PtH4 2- kernels in these clusters are locally aromatic. Based on these results, we propose that local aromaticity can be gainfully utilized as a new potential magic rule in the search for magic numbers.

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.