Charged Microdroplets as Microelectrochemical Cells for CO2 Reduction and C-C Coupling.

Charged microdroplets offer novel electrochemical environments, distinct from traditional solid-liquid or solid-liquid-gas interfaces, due to the intense electric fields at liquid-gas interfaces. In this study, we propose that charged microdroplets serve as microelectrochemical cells (MECs), enabling unique electrochemical reactions at the gas-liquid interface. Using electrospray-generated microdroplets, we achieved multielectron CO2 reduction and C-C coupling to synthesize ethanol using molecular catalysts. These catalysts effectively harness and relay electrons, enhancing the longevity of solvated electrons and enabling multielectron reactions. Importantly, we revealed the intrinsic relationship between the size and charge density of a MEC and its reaction selectivity. Employing in situ mass spectrometry, we identified reaction intermediates (molecular catalyst adducts with HCOO) and oxidation products, elucidating the CO2 reduction mechanism and the comprehensive reaction procedure. Our research underscores the promising role of charged microdroplets in pioneering new electrochemical systems.

Direct Analysis of Micro-biopsy Samples by Polarity Gradient Focusing Dip-and-Go Mass Spectrometry.

Direct analysis of micro-biopsy samples by mass spectrometry at single-cell level still faces major challenges. In this work, we developed a polarity gradient focusing dip-and-go strategy (PGF-Dip&Go) during induced electrospray ionization mass spectrometry (iESI-MS) analysis for real-time enrichment and spatial separation of compounds such as lipids, alkaloids, fatty amines, and drugs. Compared with direct iESI-MS analysis, enrichment of analytes (enrichment factor of 5.0-100.0) and spatial separation between different analytes were achieved. Owing to the enrichment effect and salt cleanup effect, the sensitivity of PGF-Dip&Go has been improved by 25-10,000 times compared with direct iESI-MS. PGF-Dip&Go has been successfully applied for the analysis of lipids in a 200 pL micro-biopsy section from an individual fish egg. Lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and triglyceride (TG) were significantly enriched and separated according to their polarity differences, proving the potential of PGF-Dip&Go to be a noninvasive and powerful analytical tool for in situ analysis of complex small volumes in the future.

In Situ Probing and Identification of Electrochemical Reaction Intermediates by Floating Electrolytic Electrospray Mass Spectrometry.

The in-depth study of electrochemical (EC) synthesis can require a powerful mass spectrometry (MS) analytical platform which can discover and identify fleeting intermediates in EC reactions. Here we report a floating electrolytic electrospray ionization (FE-ESI) strategy that can perform EC processes in a floating electrolytic cell and monitor intermediates by high-resolution MS. Compared with previous EC-MS methods, a significant advantage of FE-ESI-MS is that it allows one to modulate the electrolytic and electrospray process individually, ensuring its high sensitivity in discovering intermediates and universality to investigate redox reactions in different scenarios. This powerful platform has been successfully used to investigate the EC reductive coupling of p-tolylboronic acid and p-nitrotoluene. A series of nitrene intermediates were discovered and identified by FE-ESI-MS, indicating that a hidden mechanism involving nitrene formation might play a key role in EC reductive coupling process.

Rapid and Economical Chemoselective Metabolomics Using Boronate Ester Formation on a Monolithic Substrate.

Although chemoselective labeling strategies show great potential in in-depth description of metabolomics, the associated time and expense limit applications in high-throughput and routine analysis. We report a fast and effective chemoselective labeling strategy based on multifunctionalized monolithic probes. A rapid pH-responsive boronate ester reaction was employed to immobilize and release probe molecules from substrate in 5 min. The mesoporous surface and hierarchically porous channels of the substrate allowed for accelerated labeling reactions. Moreover, the discernible boron beacons allowed for recognition of labeled metabolites with no need for expensive isotopic encoding. This new strategy has been successfully used for submetabolome analysis of yeast cells, serum, and faeces samples, with improved sensitivity for short chain fatty acids up to 1 600 times compared with non-labeled liquid chromatography-mass spectrometry (LC-MS) methods.

Collection and Characterization by Mass Spectrometry of the Neutral Serine Octamer Generated upon Sublimation.

Serine forms neutral octameric clusters during sublimation, as demonstrated by electrostatically deflecting thermally ionized serine species from the sublimate, then gently ionizing the remaining neutrals for examination by mass spectrometry (MS). The MS results demonstrate a strong homochiral preference in the neutral octamer (measured after its gentle ionization), while the smaller serine clusters are achiral. In the initial stages of its sublimation, nonracemic solid serine generates a neutral serine monomer as the principal species in the vapor phase, with a significant enantiomeric enrichment relative to the solid. The serine monomer, when the flux is sufficient, assembles into the octamer, which displays a much higher chiral purity than the monomer. The serine octamer is separated from other neutral clusters in the sublimate by a new method based on the different distances that the clusters travel in an inert gas stream before they condense in a cooled collector. The deposited octamer is subsequently dissolved, and the solution is investigated by MS. The spectrum confirms that the collected serine octamer has undergone chiral enrichment relative to the starting solid used in the sublimation. The chiral enrichment observed in going from the serine monomer to octamer can be accommodated using a chemical model, grounded on the homochiral preference of the neutral serine octamer. Using the enantiomeric excess (ee %) of the vapor-phase monomer as the input, the model output matches the experimental octamer ee % when subliming solid serine with various initial ee % values.

Accelerated Reaction Kinetics in Microdroplets: Overview and Recent Developments.

Various organic reactions, including important synthetic reactions involving C-C, C-N, and C-O bond formation as well as reactions of biomolecules, are accelerated when the reagents are present in sprayed or levitated microdroplets or in thin films. The reaction rates increase by orders of magnitude with decreasing droplet size or film thickness. The effect is associated with reactions at the solution-air interface. A key factor is partial solvation of the reagents at the interface, which reduces the critical energy for reaction. This phenomenon is of intrinsic interest and potentially of practical value as a simple, rapid method of performing small-scale synthesis.

Reaction Acceleration at Solid/Solution Interfaces: Katritzky Reaction Catalyzed by Glass Particles.

The Katritzky reaction in bulk solution at room temperature is accelerated significantly by the surface of a glass container compared to a plastic container. Remarkably, the reaction rate is increased by more than two orders of magnitude upon the addition of glass particles with the rate increasing linearly with increasing amounts of glass. A similar phenomenon is observed when glass particles are added to levitated droplets, where large acceleration factors are seen. Evidence shows that glass acts as a "green" heterogeneous catalyst: it participates as a base in the deprotonation step and is recovered unchanged from the reaction mixture. Reaction acceleration at two separate interfaces is recognized in this study: i) air/solution phase acceleration, as is well known in microdroplets; ii) solid/solution phase, where such acceleration appears to be a new phenomenon.

Reversed Charge Transfer and Enhanced Hydrogen Spillover in Platinum Nanoclusters Anchored on Titanium Oxide with Rich Oxygen Vacancies Boost Hydrogen Evolution Reaction.

The catalytic activity of metal clusters is closely related with the support; however, knowledge on the influence of the support on the catalytic activity is scarce. We demonstrate that Pt nanoclusters (NCs) anchored on porous TiO2 nanosheets with rich oxygen vacancies (VO -rich Pt/TiO2 ) and deficient oxygen vacancies (VO -deficient Pt/TiO2 ), display significantly different catalytic activity for the hydrogen evolution reaction (HER), in which VO -rich Pt/TiO2 shows a mass activity of 45.28 A mgPt -1 at -0.1 V vs. RHE, which is 16.7 and 58.8 times higher than those of VO -deficient Pt/TiO2 and commercial Pt/C, respectively. DFT calculations and in situ Raman spectra suggest that porous TiO2 with rich oxygen vacancies can simultaneously achieve reversed charge transfer (electrons transfer from TiO2 to Pt NCs) and enhanced hydrogen spillover from Pt NCs to the TiO2 support, which leads to electron-rich Pt NCs being amenable to proton reduction of absorbed H*, as well as the acceleration of hydrogen desorption at Pt catalytic sites-both promoting the HER. Our work provides a new strategy for rational design of highly efficient HER catalysts.

High-Throughput Bioassays using "Dip-and-Go" Multiplexed Electrospray Mass Spectrometry.

A multiplexed system based on inductive nanoelectrospray mass spectrometry (nESI-MS) has been developed for high-throughput screening (HTS) bioassays. This system combines inductive nESI and field amplification micro-electrophoresis to achieve a "dip-and-go" sample loading and purification strategy that enables nESI-MS based HTS assays in 96-well microtiter plates. The combination of inductive nESI and micro-electrophoresis makes it possible to perform efficient in situ separations and clean-up of biological samples. The sensitivity of the system is such that quantitative analysis of peptides from 1-10 000 nm can be performed in a biological matrix. A prototype of the automation system has been developed to handle 12 samples (one row of a microtiter plate) at a time. The sample loading and electrophoretic clean-up of biosamples can be done in parallel within 20 s followed by MS analysis at a rate of 1.3 to 3.5 s per sample. The system was used successfully for the quantitative analysis of BACE1-catalyzed peptide hydrolysis, a prototypical HTS assay of relevance to drug discovery. IC50 values for this system were in agreement with LC-MS but recorded in times more than an order of magnitude shorter.

Nebulization Prior to Isolation, Ionization, and Dissociation of the Neutral Serine Octamer Allows Its Characterization.

Nebulization of enantiomerically mixed serine solutions, followed by ion deflection and gentle on-line protonation, is used to isolate and characterize the strongly preferred homochiral neutral serine octamer (Ser8 ). The separation of the nebulization and ionization steps and the use of the enantiomeric l-serine ion (l-d3 Ser)8 H+ as a soft protonating agent ensured that neutral (d-Ser)8 was characterized without interference from serine octamer ((d-Ser)8 H+ ) ions. MS/MS experiments showed that the ionized neutral octamer and the protonated octamer formed directly by ESI have the same structures. Experiments in which the temperature of the heated transfer tube was varied indicate dissociation of the neutral octamer to the dimer. Field-free nebulization of racemic serine forms the separate homochiral species with very high chiral selectivity. We suggest that the homochiral preference is a property of (d-Ser)8 and that the preference observed earlier for (d-Ser)8 H+ is simply an expression of this feature of the neutral cluster.

Reaction Acceleration in Thin Films with Continuous Product Deposition for Organic Synthesis.

Thin film formats are used to study the Claisen-Schmidt base-catalyzed condensation of 6-hydroxy-1-indanone with substituted benzaldehydes and to compare the reaction acceleration relative to the bulk. Relative acceleration factors initially exceeded 103 and were on the order of 102 at steady state, although the confined volume reaction was not electrostatically driven. Substituent effects were muted compared to those in the corresponding bulk and microdroplet reactions and it is concluded that the rate-limiting step at steady state is reagent transport to the interface. Conditions were found that allowed product deposition from the thin film to occur continuously as the reaction mixture was added and as the solvent evaporated. Yields of 74 % and production rates of 98 mg h-1 were reached in a very simple experimental system that could be multiplexed to greater scales.

In Situ Ion-Transmission Mass Spectrometry for Paper-Based Analytical Devices.

Current detection methods for paper-based analytical devices (PADs) rely on spectroscopic and electrochemical properties, which place special requirements on the analyte or need analyte labeling. Here, ion-transmission mass spectrometry (MS) was proposed for coupling with PADs to enable rapid in situ MS analysis of the sample on paper. The sample was analyzed directly on paper via analyte ionization by ions transmitted through the paper, generated by a low-temperature plasma probe. Prior to MS analysis, the sample can be separated by paper electrophoresis or by paper chromatography, among a variety of other features offered by PADs. The versatility of this technique was demonstrated by MS analysis of a paper microarray, a mixture of amino acids, and whole blood doped with drugs on PADs.

Pulsed Direct Current Electrospray: Enabling Systematic Analysis of Small Volume Sample by Boosting Sample Economy.

We had developed pulsed direct current electrospray ionization mass spectrometry (pulsed-dc-ESI-MS) for systematically profiling and determining components in small volume sample. Pulsed-dc-ESI utilized constant high voltage to induce the generation of single polarity pulsed electrospray remotely. This method had significantly boosted the sample economy, so as to obtain several minutes MS signal duration from merely picoliter volume sample. The elongated MS signal duration enable us to collect abundant MS(2) information on interested components in a small volume sample for systematical analysis. This method had been successfully applied for single cell metabolomics analysis. We had obtained 2-D profile of metabolites (including exact mass and MS(2) data) from single plant and mammalian cell, concerning 1034 components and 656 components for Allium cepa and HeLa cells, respectively. Further identification had found 162 compounds and 28 different modification groups of 141 saccharides in a single Allium cepa cell, indicating pulsed-dc-ESI a powerful tool for small volume sample systematical analysis.

Coupling a solid phase microextraction (SPME) probe with ambient MS for rapid enrichment and detection of phosphopeptides in biological samples.

In this study, we developed a probe-electrospray ionization method by coupling a SPME probe modified with nanosized TiO2 directly to nanoESI-MS for the phosphoproteome analysis, which demonstrated excellent selectivity and sensitivity for enrichment of phosphopeptides in complex biological samples.

Engineering a defect-rich Prussian blue analog composite for enhanced Cs+ removal performance.

Using a novel, irregular honeycombed N-doped porous carbon (NPC) as a support and defect inducer, defect-rich Zn-PBA was formed in situ and evenly anchored on the surface of NPC to obtain a defect-rich Zn-PBA/NPC composite. This composite demonstrated an ultrafast Cs+ adsorption rate that reached equilibrium within 60 s as well as excellent adsorption capacity, stability and reusability. The adsorption mechanism indicated that Cs+ was quickly adsorbed via the defect sites close to the Zn-PBA crystal face accompanied by K(OH2)+ elimination.

Rapid removal of matrices from small-volume samples by step-voltage nanoelectrospray.

Matrix unloaded: By changing from fixed-voltage (left) to step-voltage nanoelectrospray (right), the mass-spectrometric analysis of small-volume physiological samples is possible. Separation and ionization are achieved in one process, which avoids sample loss and dilution and prevents interference by the matrix. The result is high sensitivity even for samples at the nanoliter level.

Novel negative-definiteness conditions on the quadratic polynomial function with application to stability analysis of continuous time-varying delay systems.

When analyzing the stability of time-varying delay systems in view of the Lyapunov-Krasovskii functional, a quadratic polynomial function with regard to time-varying delay is always generated. And it is particularly crucial to determine the negativeness of the matrix of such a quadratic form function for obtaining an analysis result expressed in linear matrix inequalities. This paper proposes a method of tangent intersection in the delay interval segmentation, producing the generalized quadratic convex conditions by further utilizing the cross point between every two tangent lines. It reduces the conservatism of the existing conditions remarkably without requiring unexplainable adjustable parameters and additional decision variables. Benefiting from the newly proposed quadratic convex conditions, the novel stability conditions are derived, the superiority of which is demonstrated through several widely used numerical instances and single area power system PI control example.

Neophaseic acid catabolism in the 9'-hydroxylation pathway of abscisic acid in Arabidopsis thaliana.

Abscisic acid (ABA) hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance. Here, we discover a new downstream catabolite of neophaseic acid (neoPA) in the ABA 9'-hydroxyl pathway and identify it as epi-neodihydrophaseic acid (epi-neoDPA) by comparing its accurate mass, retention time, and MSn spectra with those of our chemically synthesized epi-neoDPA. Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity. In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1 (neoPA reductase 1) identified from Arabidopsis converts neoPA into epi-neoDPA. Site-directed mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1. Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants, whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines, suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis.

Pd Reaction Intermediates in Suzuki-Miyaura Cross-Coupling Characterized by Mass Spectrometry.

Palladium-catalyzed Suzuki-Miyaura (SM) coupling is widely utilized in the construction of carbon-carbon bonds. In this study, nanoelectrospray ionization mass spectrometry (nanoESI-MS) is applied to simultaneously monitor precatalysts, catalytic intermediates, reagents, and products of the SM cross-coupling reaction of 3-Br-5-Ph-pyridine and phenylboronic acid. A set of Pd cluster ions related to the monoligated Pd (0) active catalyst is detected, and its deconvoluted isotopic distribution reveals contributions from two neutral molecules. One is assigned to the generally accepted Pd(0) active catalyst, seen in MS as the protonated molecule, while the other is tentatively assigned to an oxidized catalyst which was found to increase as the reaction proceeds. Oxidative stress testing of a synthetic model catalyst 1,5-cyclooctadiene Pd XPhos (COD-Pd-XPhos) performed using FeCl3 supported this assignment. The formation and conversion of the oxidative addition intermediate during the catalytic cycle was monitored to provide information on the progress of the transmetalation step.

Reaction Acceleration Promoted by Partial Solvation at the Gas/Solution Interface.

The kinetics of organic reactions of different types in microvolumes (droplets, thin films, and sealed tubes) show effects of gas/solution interfacial area, reaction molecularity and solvent polarity. Partial solvation at the gas/solution interface is a major contributor to the 104 -fold reaction acceleration seen in bimolecular but not unimolecular reactions in microdroplets. Reaction acceleration can be used to manipulate selectivity by solvent choice.