Electrospray ionization tandem mass spectrometry of 4-aryl-3,4-dihydrocoumarins.

We have investigated the gas-phase fragmentation reactions of 11 synthetic 4-aryl-3,4-dihydrocoumarins by electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a quadrupole-time-of flight (Q-TOF) hybrid mass spectrometer. We have also estimated thermochemical data for the protonated coumarins (precursor ion A) and product ion structures by computational chemistry at a B3LYP level of theory to establish the ion structures and to rationalize the fragmentation pathways. The most abundant ions in the product ion spectra of coumarins 1-11 resulted from C8H8O2, CO2, C4H4O3, C8H10O3, C8H8O2, and CH3OH eliminations through retro-Diels-Alder (RDA) reactions, remote hydrogen rearrangements (ß-eliminations), and ß-lactone ring contraction. Although the investigated coumarins shared most of the fragmentation pathways, formation of a benzylic product ion and its corresponding tropylium ion was diagnostic of the substituents at ring C. The thermochemical data revealed that the nature and position of the substituents at ring C played a key role in the formation of this product ion and determined its relative intensity in the product ion spectrum. The results of this study contribute to knowledge of the gas-phase ion chemistry of this important class of organic compounds.

Mausolates†: Large-Cavity Chelates with Potential as Delivery Vehicles in Nuclear Medicine.

A new type of diborate clathrochelate (cage) ligand featuring nine inwardly pointing nitrogen donors that form a large, rigid cavity, termed a mausolate, is presented. The cavity size and high denticity make this an attractive delivery vehicle for large radionuclides in nuclear medicine. Metal mausolate complexes are stable to air and water (neutral pH) and display extremely high thermal stability (> 400 0C). Lanthanide uptake by the mausolate ligand occurs rapidly in solution at room temperature and once complexed, the lanthanide ions are not displaced by a 250-fold excess of a competitive lanthanide salt over more than one week.

Mechanistic study of the atomic layer deposition of cobalt: a combined mass spectrometric and computational approach.

Cobaltcarbonyl-tert-butylacetylene (CCTBA) is a conventional precursor for the selective atomic layer deposition of Co onto silicon surfaces. However, a limited understanding of the deposition mechanism of such cobalt precursors curbs rational improvements on their design for increased efficiency and tuneable selectivity. The impact of using a less reactive internal alkyne instead of a terminal alkyne was investigated using experimental and computational methods. Using electrospray-ionization mass spectrometry, the formation of CCTBA analogs and their gas phase decomposition pathways were studied. Decomposition experiments show very similar decomposition pathways between the two complexes. The internal alkyne dissociates from the Co complex at slightly lower energies than the terminal alkyne, suggesting that an internal alkynyl ligand may be more suited to low temperature ALD. In addition, transition state calculations using the nudged elastic band method confirm an increased reaction barrier between the internal alkyne and the Si-H surface bonds on Si(111). These results suggests that using a less reactive internal alkyne will result in fewer embedded carbon impurities during deposition onto Si wafers. DFT calculations using the PBE functional and periodic boundary conditions also predict increased surface binding with the metal centers of the internal alkynyl complex.

OptiMS: An Accessible Program for Automating Mass Spectrometry Parameter Optimization and Configuration.

Mass spectrometers have an enormous number of user-changeable parameters that drastically affect the observed mass spectrum. Using optimal parameters can significantly improve mass spectrometric data by increasing signal stability and signal-to-noise ratio, which decreases the limit of detection, thus revealing previously unobservable species. However, ascertaining optimal parameters is time-consuming, tedious, and made further challenging by the fact that parameters can act dependently on each other. Consequently, suboptimal parameters are frequently used during characterization, reducing the quality of results. OptiMS, an open-source, cross-platform program, was developed to simplify, accelerate, and more accurately determine optimal mass spectrometer parameters for a given system. It addresses common difficulties associated with existing software such as slow performance, high costs, and limited functionality. OptiMS efficacy was demonstrated through its application to multiple systems, quickly and successfully optimizing instrument parameters unassisted to maximize a user-defined metric, such as the intensity of a particular analyte. Additionally, among other features, OptiMS allows running of a sequence of predefined parameter configurations, reducing the workload of users wishing to obtain mass spectra under multiple sets of conditions.

Microstructural Analysis of Benzoxazine Cationic Ring-Opening Polymerization Pathways.

Herein, an evaluation of the initial step of benzoxazine polymerization is presented by mass spectrometry, with a focus on differentiating the phenoxy and phenolic products formed by distinct pathways of the cationic ring opening polymerization (ROP) mechanism of polybenzoxazine formation. The use of infrared multiple photon dissociation (IRMPD) and ion mobility spectrometry (IMS) techniques allows for differentiation of the two pathways and provides valuable insights into the ROP mechanism. The results suggest that type I pathway is favored in the initial stages of the reaction yielding the phenoxy product, while type II product should be observed at later stages when the phenoxy product would interconvert to the most stable type II phenolic product. Overall, the findings presented here provide important information on the initial step of the benzoxazine polymerization, allowing the development of optimal polymerization conditions and represents a way to evaluate other multifunctional polymerization processes.

Continuous addition kinetic elucidation: catalyst and reactant order, rate constant, and poisoning from a single experiment.

Kinetic analysis of catalytic reactions is a powerful tool for mechanistic elucidation but is often challenging to perform, limiting understanding and therefore development of these reactions. Establishing order in a catalyst is usually achieved by running several reactions at different loadings, which is both time-consuming and complicated by the challenge of maintaining consistent run-to-run experimental conditions. Continuous addition kinetic elucidation (CAKE) was developed to circumvent these issues by continuously injecting a catalyst into a reaction, while monitoring reaction progress over time. For reactions that are mth order in a single yield-limiting reactant and nth order in catalyst, a plot of reactant concentration against time has a shape dependent only on the orders m and n. Therefore, fitting experimental CAKE data (using open access code or a convenient web tool) allows the reactant and catalyst orders, rate constant, and the amount of complete catalyst inhibition to be determined from a single experiment. Kinetic information obtained from CAKE experiments showed good agreement with the literature.

Handling considerations for the mass spectrometry of reactive organometallic compounds.

Mass spectrometry is a powerful tool in disparate areas of chemistry, but its characteristic strength of sensitivity can be an Achilles heel when studying highly reactive organometallic compounds. A quantity of material suitable for mass spectrometric analysis often represents a tiny grain or a very dilute solution, and both are highly susceptible to decomposition due to ambient oxygen or moisture. This complexity can be frustrating to chemists and analysts alike: the former being unable to get spectra free of decomposition products and the latter often being poorly equipped to handle reactive samples. Fortunately, many creative solutions to such problems have been developed. This review summarizes some key methods for handling reactive samples in conjunction with the various ionization methods most frequently employed for their analysis.

A mechanistic investigation of the Pd-catalyzed cross-coupling between N-tosylhydrazones and aryl halides.

The cross-coupling of N-tosylhydrazones and aryl halides forms carbon-carbon bonds, producing 1,1-disubstituted alkenes. Though it has proven extremely useful in several fields of chemistry, its mechanism remains experimentally unexplored. Combining benchtop NMR and real-time mass spectrometry afforded the ability to monitor the catalytic intermediates as well as the rate of product formation.

Regio- and diastereoselective Pd-catalyzed aminochlorocyclization of allylic carbamates: scope, derivatization, and mechanism.

The regio- and diastereoselective synthesis of oxazolidinones via a Pd-catalyzed vicinal C-N/C-Cl bond-forming reaction from internal alkenes of allylic carbamates is reported. The oxazolidinones are obtained in yields of 44 to 95% with high to excellent diastereoselectivities (from 6 : 1 to >20 : 1 dr) from readily available precursors. This process is scalable, and the products are suitable for the synthesis of useful amino alcohols. A detailed theoretical and experimental mechanistic study was carried out to describe that the reaction proceeds through an anti-aminopalladation of the alkene followed by an oxidative C-Pd(ii) cleavage with retention of the carbon stereochemistry to yield the major diastereomer. The role of Cu(ii) in a C-Cl bond-forming mechanism step has also been proposed.

Are Methylaluminoxane Activators Sheets?

Density functional theory calculations on neutral sheet models for methylaluminoxane (MAO) indicate that these structures, containing 5-coordinate and 4-coordinate Al, are likely precursors to ion-pairs seen during the hydrolysis of trimethylaluminum (Me3 Al) in the presence of donors such as octamethyltrisiloxane (OMTS). Ionization by both methide ([Me]- ) and [Me2 Al]+ abstraction, involving this donor, were studied by polarizable continuum model calculations in fluorobenzene (PhF) and o-difluorobenzene (DFB) media. These studies suggest that low MW, 5-coordinate sheets ionize by [Me2 Al]+ abstraction, while [Me]- abstraction from Me3 Al-OMTS is the likely process for higher MW 4-coordinate sheets. Further, comparison of anion stabilities per mole of aluminoxane repeat unit (MeAlO)n , suggest that anions such as [(MeAlO)7 (Me3 Al)4 Me]- =[7,4]- are especially stable compared to higher homologues, even though their neutral precursors are unstable.

Spectroscopic Studies of Synthetic Methylaluminoxane: Structure of Methylaluminoxane Activators.

Hydrolysis of trimethylaluminum (Me3 Al) in polar solvents can be monitored by electrospray ionization mass spectrometry (ESI-MS) using the donor additive octamethyltrisiloxane [(Me3 SiO)2 SiMe2 , OMTS]. Using hydrated salts, hydrolytic methylaluminoxane (h-MAO) features different anion distributions, depending on the conditions of synthesis, and different activator contents as measured by NMR spectroscopy. Non-hydrolytic MAO was prepared using trimethylboroxine. The properties of this material, which contains incorporated boron, differ significantly from h-MAO. In the case of MAO prepared by direct hydrolysis, oligomeric anions are observed to rapidly form, and then more slowly evolve into a mixture dominated by an anion with m/z 1375 with formula [(MeAlO)16 (Me3 Al)6 Me]- . Theoretical calculations predict that sheet structures with composition (MeAlO)n (Me3 Al)m are favoured over other motifs for MAO in the size range suggested by the ESI-MS experiments. A possible precursor to the m/z 1375 anion is a local minimum based on the free energy released upon hydrolysis of Me3 Al.

Dynamic Ion Speciation during the Hydrolysis of Aryltrifluoroborates*.

Organotrifluoroborates serve as coupling partners during transmetalation in the Suzuki-Miyaura reaction but require hydrolysis prior to the coupling reaction. Their anionic nature allows study of their hydrolysis by electrospray ionization mass spectrometry (ESI-MS) through real-time monitoring, complemented by pH analysis. The induction period varied according to the borates employed, and a dynamic series of equilibria for numerous ions was observed during hydrolysis. We found that the induction periods and reaction rates were sensitive to the R group of the borates, the shape of the reaction vessel, and stir rate.

Trichloro(Dinitrogen)Platinate(II).

Zeise's salt, [PtCl3 (H2 C=CH2 )]- , is the oldest known organometallic complex, featuring ethylene strongly bound to a platinum salt. Many derivatives are known, but none involving dinitrogen, and indeed dinitrogen complexes are unknown for both platinum and palladium. Electrospray ionization mass spectrometry of K2 [PtCl4 ] solutions generate strong ions corresponding to [PtCl3 (N2 )]- , the identity of which was confirmed through ion-mobility spectrometry and MS/MS experiments that proved it to be distinct from its isobaric counterparts [PtCl3 (C2 H4 )]- and [PtCl3 (CO)]- . Computational analysis established a gas-phase platinum-dinitrogen bond strength of 116 kJ mol-1 , substantially weaker than the ethylene and carbon monoxide analogues but stronger than for polar solvents such as water, methanol and dimethylformamide, and strong enough that the calculated N-N bond length of 1.119 Šrepresents weakening to a degree typical of isolated dinitrogen complexes.

Real-time analysis of methylalumoxane formation.

Methylalumoxane (MAO), a perennially useful activator for olefin polymerization precatalysts, is famously intractable to structural elucidation, consisting as it does of a complex mixture of oligomers generated from hydrolysis of pyrophoric trimethylaluminum (TMA). Electrospray ionization mass spectrometry (ESI-MS) is capable of studying those oligomers that become charged during the activation process. We have exploited that ability to probe the synthesis of MAO in real time, starting less than a minute after the mixing of H2O and TMA and tracking the first half hour of reactivity. We find that the process does not involve an incremental build-up of oligomers; instead, oligomerization to species containing 12-15 aluminum atoms happens within a minute, with slower aggregation to higher molecular weight ions. The principal activated product of the benchtop synthesis is the same as that observed in industrial samples, namely [(MeAlO)16(Me3Al)6Me]-, and we have computationally located a new sheet structure for this ion 94 kJ mol-1 lower in Gibbs free energy than any previously calculated.

Step-by-step real time monitoring of a catalytic amination reaction.

The multiple reaction monitoring mode of a triple quadrupole mass spectrometer is used to examine the Buchwald-Hartwig amination reaction at 0.1% catalyst loading in real-time using sequential addition of reagents to probe the individual steps in the cycle. This is a powerful new method for probing reactions under realistic conditions.

Structure, Anion, and Solvent Effects on Cation Response in ESI-MS.

The abundance of an ion in an electrospray ionization mass spectrum is dependent on many factors beyond just solution concentration. Even in cases where the analytes of interest are permanently charged (under study here are ammonium and phosphonium ions) and do not rely on protonation or other chemical processes to acquire the necessary charge, factors such as cation structure, molecular weight, solvent, and the identity of the anion can affect results. Screening of a variety of combinations of cations, anions, and solvents provided insight into some of the more important factors. Rigid cations and anions that conferred high conductivity tended to provide the highest responses. The solvent that most closely reflected actual solution composition was acetonitrile, while methanol, acetonitrile/water, and dichloromethane produced a higher degree of discrimination between different ions. Functional groups that had affinity for the solvent tended to depress response. These observations will provide predictive power when accounting for analytes that for reasons of high reactivity can not be isolated.

Assigning the ESI mass spectra of organometallic and coordination compounds.

Electrospray ionization mass spectrometry (ESI-MS) is a useful technique for solving organometallic and coordination chemistry characterization problems that are difficult to address using traditional methods. However, assigning the ESI mass spectra of such compounds can be challenging, and the considerations involved in doing so are quite different from assigning the mass spectra of purely organic samples. This is a tutorial article for organometallic/coordination chemists using ESI-MS to analyze pure compounds or reaction mixtures. The fundamentals of assigning ESI mass spectra are discussed within the context of organometallic and coordination systems. The types of ions commonly observed by ESI-MS are categorized and described. Finally, a step-by-step guide for the assignment of organometallic and coordination chemistry ESI mass spectra is provided along with two case studies.

PythoMS: A Python Framework To Simplify and Assist in the Processing and Interpretation of Mass Spectrometric Data.

Mass spectrometric data are copious and generate a processing burden that is best dealt with programmatically. PythoMS is a collection of tools based on the Python programming language that assist researchers in creating figures and video output that is informative, clear, and visually compelling. The PythoMS framework introduces a library of classes and a variety of scripts that quickly perform time-consuming tasks: making proprietary output readable; binning intensity vs time data to simulate longer scan times (and hence reduce noise); calculating theoretical isotope patterns and overlaying them in histogram form on experimental data (an approach that works even for overlapping signals); rendering videos that enable zooming into the baseline of intensity vs time plots (useful to make sense of data collected over a large dynamic range) or that depict the evolution of different species in a time-lapse format; calculating aggregates; and providing a quick first-pass at identifying fragments in MS/MS spectra. PythoMS is a living project that will continue to evolve as additional scripts are developed and deployed.

Competitive Ligand Exchange and Dissociation in Ru Indenyl Complexes.

Kinetic profiles obtained from monitoring the solution-phase substitution chemistry of [Ru(η5-indenyl)(NCPh)(PPh3)2]+ (1) by both electrospray ionization mass spectrometry and 31P{1H} NMR are essentially identical, despite an enormous difference in sample concentrations for these complementary techniques. These studies demonstrate dissociative substitution of the NCPh ligand in 1. Competition experiments using different secondary phosphine reagents provide a ranking of phosphine donor abilities at this relatively crowded half-sandwich complex: PEt2H > PPh2H ≫ PCy2H. The impact of steric congestion at Ru is evident also in reactions of 1 with tertiary phosphines; initial substitution products [Ru(η5-indenyl)(PR3)(PPh3)2]+ rapidly lose PPh3, enabling competitive re-coordination of NCPh. Further solution experiments, relevant to the use of 1 in catalytic hydrophosphination, show that PPh2H out-competes PPh2CH2CH2CO2Bu t (the product of hydrophosphination of tert-butyl acrylate by PPh2H) for coordination to Ru, even in the presence of a 10-fold excess of the tertiary phosphine. Additional information on relative phosphine binding strengths was obtained from gas-phase MS/MS experiments, including collision-induced dissociation experiments on the mixed phosphine complexes [Ru(η5-indenyl)PP'P″]+, which ultimately appear in solution during the secondary phosphine competition experiments. Unexpectedly, unsaturated complexes [Ru(η5-indenyl)(PR2H)(PPh3)]+, generated in the gas-phase, undergo preferential loss of PR2H. We propose that competing orthometallation of PPh3 is responsible for the surprising stability of the [Ru(η5-indenyl)(PPh3)]+ fragment under these conditions.

Modifying methylalumoxane via alkyl exchange.

Methylalumoxane (MAO) ionizes highly selectively in the presence of octamethyltrisiloxane (OMTS) to generate [Me2Al·OMTS]+ [(MeAlO)16(Me3Al)6Me]-. We can take advantage of this transformation to examine the reactivity of a key component of MAO using electrospray ionization mass spectrometry (ESI-MS), and here we describe the reactivity of this pair of ions with other trialkyl aluminum (R3Al) components. Using continuous injection methods, we found Et3Al to exchange much faster and extensively at room temperature in fluorobenzene (t½âˆ¼2 s, up to 25 exchanges of Me for Et) than iBu3Al (t½âˆ¼40 s, up to 11 exchanges) or Oct3Al (t½âˆ¼200 s, up to 7 exchanges). The exchanges are reversible and the methyl groups on the cation are also observed to exchange with the added R3Al species. These results point to the reactive components of MAO having a structure that deviates significantly from the cage-like motifs studied to date.