Huaming Sheng

Characterization of organosolv switchgrass lignin by using high performance liquid chromatography/high resolution tandem mass spectrometry using hydroxide-doped negative-ion mode electrospray ionization

Lignin is an aromatic biopolymer that may yield valuable chemicals currently obtained solely from petroleum. However, extraction of lignin by using traditional methods, such as organosolv extraction, produces very complex mixtures. Molecular level characterization of the major components is essential to be able to rationally tailor methodology for the conversion of these mixtures to transportation fuel and valuable chemicals. In this study, high performance liquid chromatography/high resolution tandem mass spectrometry (HPLC/MSn) was used to obtain molecular weight, elemental composition and structural information for the major components in an organosolv lignin sample. HPLC/MSn coupled with hydroxide-doped electrospray ionization was used to identify the structures of the major components by using a Thermo Scientific linear quadrupole ion trap-Fourier transform ion cyclotron resonance hybrid mass spectrometer (LQIT/FT-ICR). The results reported here demonstrate that the major products of organosolv extraction are low molecular weight compounds, including monomeric and dimeric lignin units, with various functionalities.

Fast pyrolysis of 13C-labeled cellobioses: gaining insights into the mechanisms of fast pyrolysis of carbohydrates.

A fast-pyrolysis probe/tandem mass spectrometer combination was utilized to determine the initial fast-pyrolysis products for four different selectively (13)C-labeled cellobiose molecules. Several products are shown to result entirely from fragmentation of the reducing end of cellobiose, leaving the nonreducing end intact in these products. These findings are in disagreement with mechanisms proposed previously. Quantum chemical calculations were used to identify feasible low-energy pathways for several products. These results provide insights into the mechanisms of fast pyrolysis of cellulose.

Identification of the sulfone functionality in protonated analytes via ion/molecule reactions in a linear quadrupole ion trap mass spectrometer.

A tandem mass spectrometric method is presented for the rapid identification of drug metabolites that contain the sulfone functional group. This method is based on a gas-phase ion/molecule reaction of protonated sulfone analytes with trimethyl borate (TMB) that yields a diagnostic product ion, adduct-Me2O, at high reaction efficiency. A variety of compounds with different functional groups, such as sulfoxides, hydroxylamines, N-oxides, anilines, phenol, an aliphatic amine, and an aliphatic alcohol, were examined to probe the selectivity of this reaction. Except for protonated sulfones, most of the protonated compounds react very slowly or not at all with TMB. Most importantly, none of them give the adduct-Me2O product. A mechanism that explains the observed selectivity is proposed for the diagnostic reaction and is supported by quantum chemical calculations. The reaction was tested with the anti-inflammatory drug sulindac and its metabolite, sulindac sulfone, which were readily distinguished. The presence of other functionalities in addition to sulfone was found not to influence the diagnostic reactivity.

On the factors that control the reactivity of meta-benzynes

The reactivities of eleven 3,5-didehydropyridinium and six 2,4-didehydropyridinium cations toward cyclohexane were examined in the gas phase by using Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometry as well as high-level quantum chemical calculations. The results unequivocally demonstrate that the reactivity of meta-benzyne analogs can be “tuned” from more radical-like to less radical-like by changing the type and position of substituents. For example, σ-acceptor substituents at the 4-position and π-donor substituents at the 2-position in 3,5-didehydropyridinium cations partially decouple the biradical electrons, which results in lower energy transition states, and faster radical reactions. In contrast, σ-acceptors at the 2-position and π-donors at the 4-position in 3,5-didehydropyridinium cations cause stronger coupling between the biradical electrons, which results in lower radical reactivity. Three main factors are found to control the reactivity of these biradicals: (1) the energy required to distort the minimum energy dehydrocarbon atom separation to the separation of the transition state, (2) the S–T splitting at the separation of the transition state, and (3) the electron affinity at the separation of the transition state.

Characterization of aromatic organosulfur model compounds relevant to fossil fuels by using atmospheric pressure chemical ionization with CS2 and high‐resolution tandem mass spectrometry

RATIONALE The chemistry of desulfurization involved in processing crude oil is greatly dependent on the forms of sulfur in the oil. Sulfur exists in different chemical bonding environments in fossil fuels, including those in thiophenes and benzothiophenes, thiols, sulfides, and disulfides. In this study, the fragmentation behavior of the molecular ions of 17 aromatic organosulfur compounds with various functionalities was systematically investigated by using high-resolution tandem mass spectrometry. METHODS Multiple-stage tandem mass spectrometric experiments were carried out using a linear quadrupole ion trap (LQIT) equipped with an atmospheric pressure chemical ionization (APCI) source. (+)APCI/CS2 was used to generate stable dominant molecular ions for all the compounds studied except for three sulfides that also showed abundant fragment ions. The LQIT coupled with an orbitrap mass spectrometer was used for elemental composition analysis, which facilitated the identification of the neutral molecules lost during fragmentation. RESULTS The characteristic fragment ions generated in MS(2) and MS(3) experiments provide clues for the chemical bonding environment of sulfur atoms in the examined compounds. Upon collision-induced dissociation (CID), the molecular ions can lose the sulfur atom in a variety of ways, including as S (32 Da), HS(•) (33 Da), H2 S (34 Da), CS (44 Da), (•) CHS (45 Da) and CH2 S (46 Da). These neutral fragments are not only indicative of the presence of sulfur, but also of the type of sulfur present in the compound. Generally, losses of HS(•) and H2 S were found to be associated with compounds containing saturated sulfur functionalities, while losses of S, CS and (•) CHS were more common for heteroaromatic sulfur compounds. CONCLUSIONS High-resolution tandem mass spectrometry with APCI/CS2 ionization is a viable approach to determining the types of organosulfur compounds. It can potentially be applied to analysis of complex mixtures, which is beneficial to improving the desulfurization process of fossil fuels. Copyright

Identification of N-Oxide and Sulfoxide Functionalities in Protonated Drug Metabolites by Using Ion–Molecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer

The in vivo oxidation of sulfur and nitrogen atoms in many drugs into sulfoxide and N-oxide functionalities is a common biotransformation process. Unfortunately, the unambiguous identification of these metabolites can be challenging. In the present study, ion-molecule reactions of tris(dimethylamino)borane followed by collisionally activated dissociation (CAD) in an ion trap mass spectrometer are demonstrated to allow the identification of N-oxide and sulfoxide functionalities in protonated polyfunctional drug metabolites. Only ions with N-oxide or sulfoxide functionality formed diagnostic adducts that had lost dimethyl amine (DMA). This was demonstrated even for an analyte that contains a substantially more basic functionality than the functional group of interest. CAD of the diagnostic product ions (M) resulted mainly in type A (M - DMA) and B fragment ions (M - HO-B(N(CH3)2)2) for N-oxides, but sulfoxides also formed diagnostic C ions (M - O═BN(CH3)2), thus allowing differentiation of the functionalities. Some protonated analytes yielded abundant TDMAB adducts that had lost two DMA molecules instead of just one. This provides information on the environment of the N-oxide and sulfoxide functionalities. Quantum chemical calculations were performed to explore the mechanisms of the above-mentioned reactions. The method can be implemented on HPLC for real drug analysis.

Mass spectrometric identification of the N‐monosubstituted N‐hydroxylamino functionality in protonated analytes via ion/molecule reactions in tandem mass spectrometry

RATIONALE N-Monosubstituted hydroxylamines correspond to an important class of metabolites for many bioactive molecules. In this study, a tandem mass spectrometric method based on ion/molecule reactions was developed for the identification of compounds with the N-monosubstituted hydroxylamino functionality. METHODS The diagnostic ion/molecule reaction occurs between protonated analytes with 2-methoxypropene (MOP) inside a linear quadrupole ion trap mass spectrometer. RESULTS Most protonated compounds with N-monosubstituted and disubstituted hydroxylamino and oxime functional groups react with MOP via proton transfer and formation of a stable adduct in a linear quadrupole ion trap mass spectrometer. However, only protonated compounds with N-monosubstituted hydroxylamino groups form the characteristic MOP adduct-MeOH product. Possible mechanisms of this reaction are discussed. CONCLUSIONS A method based on functional group-selective ion/molecule reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated to allow the identification of protonated compounds with the N-monosubstituted hydroxylamino functionality. Only N-monosubstituted hydroxylamines react with MOP via formation of an adduct that has eliminated methanol.

Gas-phase ion-molecule reactions for the identification of the sulfone functionality in protonated analytes in a linear quadrupole ion trap mass spectrometer.

RATIONALE The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion-molecule reactions was developed. METHODS A phosphorus-containing reagent, trimethyl phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer. The reaction products and reaction efficiencies were measured. RESULTS Only protonated sulfone model compounds were found to react with TMP to form a characteristic [TMP adduct-MeOH] product ion. All other protonated compounds investigated, with functionalities such as sulfoxide, N-oxide, hydroxylamino, keto, carboxylic acid, and aliphatic and aromatic amino, only react with TMP via proton transfer and/or addition. The specificity of the reaction was further demonstrated by using a sulfoxide-containing anti-inflammatory drug, sulindac, as well as its metabolite sulindac sulfone. CONCLUSIONS A method based on functional group-selective ion-molecule reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated for the identification of the sulfone functionality in protonated analytes. A characteristic [TMP adduct-MeOH] product ion was only formed for the protonated sulfone analytes. The applicability of the TMP reagent in identifying sulfone functionalities in drug metabolites was also demonstrated. Copyright

Alkali Cation Chelation in Cold β-O-4 Tetralignol Complexes.

We employ cold ion spectroscopy (UV action and IR-UV double resonance) in the gas phase to unravel the qualitative structural elements of G-type alkali metal cationized (X = Li(+), Na(+), K(+)) tetralignol complexes connected by β-O-4 linkages. The conformation-specific spectroscopy reveals a variety of conformers, each containing distinct infrared spectra in the OH stretching region, building on recent studies of the neutral and alkali metal cationized β-O-4 dimers. The alkali metal ion is discovered to bind in penta-coordinate pockets to ether and OH groups involving at least two of the three β-O-4 linkages. Different binding sites are distinguished from one another by the number of M(+)···OH···O interactions present in the binding pocket, leading to characteristic IR transitions appearing below 3550 cm(-1). This interaction is mitigated in the major conformer of the K(+) adduct, demonstrating a clear impact of the size of the charge center on the three-dimensional structure of the tetramer.

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.