Characterization of 2-Butanone Peroxide Oligomeric Profiles and Their Associated Gas-Phase and Solution-Phase Rearrangement Products by Electrospray Ionization Mass Spectrometry for Forensic Applications.

2-Butanone peroxide (also known as methyl ethyl ketone peroxide, MEKP) has applications as a cross-linker in the chemical industry and is also encountered as a homemade primary high explosive; therefore, it is of interest to both process chemists and forensic examiners. Specifically for forensic applications, we demonstrate that when traditional synthetic procedures, available to any hobbyist, are utilized to generate MEKP, oligomeric peroxide units ( ≤ 12), along with several other oligomeric byproduct distributions, are readily observed by liquid chromatography-mass spectrometry (LC-MS). These oligomeric byproducts correspond to the formation of methyl/ethyl ketone end group(s) at the oligomer end group (i.

Online Bipolar Dual Spray for the Charge State Reduction and Characterization of Complex Synthetic Polymers.

Charge reduction mass spectrometry (CR/MS) hyphenated to liquid chromatography (LC) couples liquid-phase compound separation and mass spectral decompression to resolve and characterize multicomponent systems. LC/CR/MS has proven to be effective for complex mixture analysis, particularly synthetic polymers. A newer charge manipulation approach called bipolar dual spray has previously been demonstrated to reduce the observed charge state distribution of ammoniated polyethene glycol.

Identification of diagnostic metabolic signatures in clear cell renal cell carcinoma using mass spectrometry imaging.

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of kidney cancer. Intraoperative frozen section (IFS) analysis is used to confirm the diagnosis during partial nephrectomy. However, surgical margin evaluation using IFS analysis is time consuming and unreliable, leading to relatively low utilization.

Microdroplet Fusion Chemistry for Charge State Reduction of Synthetic Polymers via Bipolar Dual Spray with Anionic Reagents.

Microdroplet fusion chemistry is an emerging area of analyte manipulation that utilizes the ion source region of a mass spectrometer to covalently derivatize or manipulate the charge state distribution. This technique utilizes two electrospray emitters in close proximity, where the droplets from each electrospray plume fuse and undergo the subsequent chemistry. In this study, microdroplet fusion chemistry via bipolar dual spray has demonstrated the ability to reduce the average charge state of polyethylene glycol (PEG) cations using anionic reagents.

Mechanistic Analysis of the C-H Amination Reaction of Menthol by CuBr and Selectfluor.

The mechanism of the Ritter-type C-H amination reaction of menthol with acetonitrile using CuBr, Selectfluor, and Zn(OTf), first disclosed by Baran and coworkers in 2012, was studied using a combination of online electrospray ionization mass spectrometry, continuous UV/vis spectrometric monitoring, and density functional theory calculations. In addition to corroborating Baran's original mechanistic proposal, these studies uncovered a second pathway to product formation, which likely only occurs in microdroplets. DFT calculations show that neither pathway has a barrier that is greater than 6.

Microdroplets Accelerate Ring Opening of Epoxides.

The nucleophilic opening of an epoxide is a classic organic reaction that has widespread utility in both academic and industrial applications. We have studied the reaction of limonene oxide with morpholine to form 1-methyl-2-morpholino-4-(prop-1-en-2-yl) cyclohexan-1-ol in bulk solution and in electrosprayed microdroplets with a 1:1 v/v water/methanol solvent system. We find that even after 90 min at room temperature, there is no product detected by nuclear magnetic resonance spectroscopy in bulk solution whereas in room-temperature microdroplets (2-3 μm in diameter), the yield is already 0.

"On-Droplet" Chemistry: The Cycloaddition of Diethyl Azodicarboxylate and Quadricyclane.

Sharpless and co-workers previously studied the [2σ+2σ+2π] cycloaddition of diethyl azodicarboxylate (DEAD) and quadricyclane and reported that the addition of water to the neat reagents caused an acceleration in the reaction rate, giving birth to what has been called "on-water" chemistry. We have examined the same reaction in aqueous microdroplets (ca. 5 μm diameter) and find that the cycloaddition reaction is accelerated even further (by a factor of 10 ) compared to that of the "on-water" reaction reported previously.

Simultaneous Online Monitoring of Multiple Reactions Using a Miniature Mass Spectrometer.

Advances in chemical sampling using miniature mass spectrometer technology are used to monitor slow reactions at a frequency of ca. 180 h (on the Mini 12) with no sample carryover and with inline derivatization in the case of poorly ionizing compounds. Moreover, we demonstrate high reproducibility with a relative error of less than 10% for major components.

Fischer Indole Synthesis in the Gas Phase, the Solution Phase, and at the Electrospray Droplet Interface.

Previous reports have shown that reactions occurring in the microdroplets formed during electrospray ionization can, under the right conditions, exhibit significantly greater rates than the corresponding bulk solution-phase reactions. The observed acceleration under electrospray ionization could result from a solution-phase, a gas-phase, or an interfacial reaction. This study shows that a gas-phase ion/molecule (or ion/ion) reaction is not responsible for the observed rate enhancement in the particular case of the Fischer indole synthesis.

Organic Reactions in Microdroplets: Reaction Acceleration Revealed by Mass Spectrometry.

The striking finding that reaction acceleration occurs in confined-volume solutions sets up an apparent conundrum: Microdroplets formed by spray ionization can be used to monitor the course of bulk-phase reactions and also to accelerate reactions between the reagents in such a reaction. This Minireview introduces droplet and thin-film acceleration phenomena and summarizes recent methods applied to study accelerated reactions in confined-volume, high-surface-area solutions. Conditions that dictate either simple monitoring or acceleration are reconciled in the occurrence of discontinuous and complete desolvation as the endpoint of droplet evolution.

Accelerated hydrazone formation in charged microdroplets.

Rationale: Electrospray ionization-mass spectrometry (ESI-MS) is an emerging tool for reaction monitoring. It can be accompanied by reaction acceleration in charged droplets.

Methods: The time course of the bulk reaction of indoline-2,3-dione with phenylhydrazine in methanol to produce 3-(2- phenylhydrazono)indolin-2-one was monitored by ESI.

Accelerated Chemical Reactions and Organic Synthesis in Leidenfrost Droplets.

Leidenfrost levitated droplets can be used to accelerate chemical reactions in processes that appear similar to reaction acceleration in charged microdroplets produced by electrospray ionization. Reaction acceleration in Leidenfrost droplets is demonstrated for a base-catalyzed Claisen-Schmidt condensation, hydrazone formation from precharged and neutral ketones, and for the Katritzky pyrylium into pyridinium conversion under various reaction conditions. Comparisons with bulk reactions gave intermediate acceleration factors (2-50).

On-line chiral analysis using the kinetic method.

Chiral analysis of constituents in solution-phase reaction mixtures can be performed by tandem mass spectrometry using the kinetic method to determine the enantiomeric excess (ee). Simply diluting an aliquot of a reaction mixture, adjusting the pH, and adding reagents necessary to form a chiral cluster ion allows chiral analysis. The product of a stereospecific N-selective alkylation reaction, 2-(3-(2-methoxyethoxy)-5-oxo-1,6-naphthyridin-6(5H)-yl)propanoic acid, was monitored for ee during the course of reaction, and it showed the expected inversion without ee erosion.

Accelerated Hantzsch electrospray synthesis with temporal control of reaction intermediates.

Complex chemical reactions can occur in electrosprayed droplets on the millisecond time scale. The Hantzsch synthesis of 1,4-dihydropyridines was studied in this way using on-line mass spectral analysis to optimize conditions and characterize the product mixture. Changing the distance between the nanospray source and the MS inlet allowed exploration of reaction progress as a function of droplet time-of-flight.

Mass spectrometry in the home and garden.

Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization.