Polar Effects Control the Gas-Phase Reactivity of para-Benzyne Analogs.

We report herein a gas-phase reactivity study on a para-benzyne cation and its three cyano-substituted, isomeric derivatives performed using a dual-linear quadrupole ion trap mass spectrometer. All four biradicals were found to undergo primary and secondary radical reactions analogous to those observed for the related monoradicals, indicating the presence of two reactive radical sites. The reactivity of all biradicals is substantially lower than that of the related monoradicals, as expected based on the singlet ground states of the biradicals. The cyano-substituted biradicals show substantially greater reactivity than the analogous unsubstituted biradical. The greater reactivity is rationalized by the substantially greater (calculated) electron affinity of the radical sites of the cyano-substituted biradicals, which results in stabilization of their transition states through polar effects. This finding is in contrast to the long-standing thinking that the magnitude of the singlet-triplet splitting controls the reactivity of para-benzynes.

Polar Effects Control the Gas-phase Reactivity of Charged para-Benzyne Analogs.

The gas-phase reactivity of charged para-benzynes is entirely unexplored as they and/or their precursors tend to undergo ring-opening upon their generation. We report here a gas-phase reactivity study of two such benzynes, the 2,5-didehydropyridinium and 5,8-didehydroisoquinolinium cations, generated in a modified dual-linear quadrupole ion trap (DLQIT) mass spectrometer. Both biradicals were found to form diagnostic products with organic molecules, indicating the presence of two radical sites. As opposed to earlier predictions that the singlet-triplet (S-T) splitting controls the radical reactivity of such species, the 2,5-didehydropyridinium cation reacts much faster in spite of its larger S-T splitting. Calculated vertical electron affinities of the radical sites of the para-benzynes, a parameter related to the polarity of the transition states of their reactions, appears to be the most important reactivity controlling factor.

A differentially pumped dual linear quadrupole ion trap (DLQIT) mass spectrometer: a mass spectrometer capable of MS(n) experiments free from interfering reactions.

A novel differentially pumped dual linear quadrupole ion trap (DLQIT) mass spectrometer was designed and built to facilitate tandem MS experiments free from interfering reactions. The instrument consists of two differentially pumped Thermo Scientific linear quadrupole ion trap (LQIT) systems that have been connected via an ion transfer octupole encased in a machined manifold. Tandem MS experiments can be performed in the front trap and then the resulting product ions can be transferred via axial ejection into the back trap for further, independent tandem MS experiments in a differentially pumped area. This approach allows the examination of consecutive collision-activated dissociation (CAD) and ion-molecule reactions without unwanted side reactions that often occur when CAD and ion-molecule reactions are examined in the same space. Hence, it greatly facilitates investigations of ion structures. In addition, the overall lower pressure of the DLQIT, as compared to commercial LQIT instruments, results in a reduction of unwanted side reactions with atmospheric contaminants, such as water and oxygen, in CAD and ion-molecule experiments.

Experimental and computational studies on the formation of three para-benzyne analogues in the gas phase.

Experimental and computational studies on the formation of three gaseous, positively-charged para-benzyne analogues in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer are reported. The structures of the cations were examined by isolating them and allowing them to react with various neutral reagents whose reactions with aromatic carbon-centered σ-type mono- and biradicals are well understood. Cleavage of two iodine-carbon bonds in N-deuterated 1,4-diiodoisoquinolinium cation by collision-activated dissociation (CAD) produced a long-lived cation that showed nonradical reactivity, which was unexpected for a para-benzyne. However, the reactivity closely resembles that of an isomeric enediyne, N-deuterated 2-ethynylbenzonitrilium cation. A theoretical study on possible rearrangement reactions occurring during CAD revealed that the cation formed upon the first iodine atom loss undergoes ring-opening before the second iodine atom loss to form an enediyne instead of a para-benzyne. Similar results were obtained for the 5,8-didehydroisoquinolinium cation and the 2,5-didehydropyridinium cation. The findings for the 5,8-didehydroisoquinolinium cation are in contradiction with an earlier report on this cation. The cation described in the literature was regenerated by using the literature method and demonstrated to be the isomeric 5,7-didehydro-isoquinolinium cation and not the expected 5,8-isomer.

Reactivity of the 4,5-didehydroisoquinolinium cation.

The chemical properties of a 1,8-didehydronaphthalene derivative, the 4,5-didehydroisoquinolinium cation, were examined in the gas phase in a dual-cell Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. This is an interesting biradical because it has two radical sites in close proximity, yet their coupling is very weak. In fact, the biradical is calculated to have approximately degenerate singlet and triplet states. This biradical was found to exclusively undergo radical reactions, as opposed to other related biradicals with nearby radical sites. The first bond formation occurs at the radical site in the 4-position, followed by that in the 5-position. The proximity of the radical sites leads to reactions that have not been observed for related mono- or biradicals. Interestingly, some ortho-benzynes have been found to yield similar products. Since ortho-benzynes do not react via radical mechanisms, these products must be especially favorable thermodynamically.

Carbon disulfide reagent allows the characterization of nonpolar analytes by atmospheric pressure chemical ionization mass spectrometry.

While atmospheric pressure ionization methodologies have revolutionized the mass spectrometric analysis of nonvolatile analytes, limitations native to the chemistry of these methodologies hinder or entirely inhibit the analysis of certain analytes, specifically, many nonpolar compounds. Examination of various analytes, including asphaltene and lignin model compounds as well as saturated hydrocarbons, demonstrates that atmospheric pressure chemical ionization (APCI) using CS(2) as the reagent produces an abundant and stable molecular ion (M(+•)) for all model compounds studied, with the exception of completely saturated aliphatic hydrocarbons and the two amino acids tested, arginine and phenylalanine. This reagent substantially broadens the applicability of mass spectrometry to nonvolatile nonpolar analytes and also facilitates the examination of radical cation chemistry by mass spectrometry.

Identification of the carboxylic acid functionality by using electrospray ionization and ion-molecule reactions in a modified linear quadrupole ion trap mass spectrometer.

A mass spectrometric method has been developed for the identification of the carboxylic acid functional group in analytes evaporated and ionized by electrospray ionization (ESI). This method is based on gas-phase ion-molecule reactions of ammoniated ([M + NH4]+) and sodiated ([M + Na]+) analyte molecules with trimethyl borate (TMB) in a modified linear quadrupole ion trap mass spectrometer. The diagnostic reaction involves addition of the deprotonated analyte to TMB followed by the elimination of methanol. A variety of analytes with different func-tionalities were examined, and this reaction was only observed for molecules containing the carboxylic acid functionality. The selectivity of the reaction is attributed to the acidic hydrogen present in the carboxylic acid group, which provides the proton necessary for the elimination of methanol. The diagnostic products are easily identified based on the m/z value of the product ion, which is 72 Th (thomson) greater than the m/z value of the charged analyte, and also by the character-istic isotope pattern of boron. The applicability of this method for pharmaceutical analysis was demonstrated for three nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen, and ketoprofen.