An experimental and computational study on the dissociation behavior of hydroxypyridine N‐oxides in atmospheric pressure ionization mass spectrometry

Abstract

A tandem mass spectrometric study of protonated isomeric hydroxypyridine N-oxides was carried out with a hybrid quadrupole/time-of-flight mass spectrometer coupled with different atmospheric pressure ionization sources. The behavior observed in the collision-induced dissociation (CID) mass spectra of the parent cations, was similar irrespective of the source employed. However, there were intrinsic differences in the intensities of the two fragments observed for each isomer. The major fragment because of elimination of a hydroxyl radical, dominated the CID spectra (in contrast with weaker water loss) at different energy thresholds. Therefore, it was possible to differentiate both isomers at collision energies above 13 eV by comparing the ratio of intensities of the major fragment relative to the precursor cation. In addition, quantum chemical calculations at the B3LYP/6-31 + + G(d,p) level of theory were performed for the protonated isomers of hydroxypyridine N-oxide and their radical cation products in order to gain insight into the major routes of dissociation. The results suggest that dissociation from the lowest triplet excited state of the protonated species would provide a reasonable rationalization for the difference in behavior of both isomers.

Differentiation of Isomeric HydroxypyridineN-Oxides Using Metal Complexation and Electrospray Ionization Mass Spectrometry

“…In this context, local reactivity indices such as the atomic nucleophilic indices (f k -), also known as electrophilic Fukui functions, provide an interesting alternative way to identify the most probable sites of protonation [19]. Recently, this methodology has been employed to identify the protonation sites in a series of natural and synthetic compounds [6,29,30].…”

“…It should be mentioned that in a previous work [6], we performed conformational studies of the protonated hydroxypyridine N-oxides 1 and 2 at the B3LYP/6-31++G(d,p) level of theory, finding two conformers for each isomer. In the stable conformations, the protonated oxygen group (hydroxyl) substituent was found to be coplanar with the aromatic ring, whereas the protonated oxygen group of the N-oxide moiety was oriented almost perpendicular to the aromatic ring, except when a hydrogen bond may occur in the structure, where was found to be coplanar.…”

“…For example, the similarity of the tandem mass spectra of protonated 8-hydroxyquinoline and quinoline N-oxide obtained by ESI showed that these isomeric oxygenated compounds were indistinguishable by this method [5]. In a previous work we have reported the differentiation of hydroxypyridine N-oxide isomers by analyzing the dissociation behavior in positive-ion mode atmospheric pressure mass spectrometry, employing ESI as well as atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) sources [6].…”

Decarboxylative Coupling Reaction in ESI(−)-MS/MS of 4-Nitrobenzyl 4-Hydroxybenzoates: Triplet Ion–Neutral Complex-Mediated 4-Nitrobenzyl Transfer

“…For example, the optimized transition state 1-a-TS3 in path 3 shows a fourmembered ring transfer of the nitrobenzyl moiety to the ipso position of the benzoate group with concomitant loss of CO 2 ; the energy barrier is 215.9 kJ/mol ( Figure 2). However, DFT methods fail to identify the transition state geometry along the reaction coordinates in homolytic reactions (e.g., paths 1 and 2) because of difficulties in treating self-interactions of electrons [17,18]. Radical formation from closed-shell ions via an electronically excited state has been reported [12,[16][17][18].…”

“…However, DFT methods fail to identify the transition state geometry along the reaction coordinates in homolytic reactions (e.g., paths 1 and 2) because of difficulties in treating self-interactions of electrons [17,18]. Radical formation from closed-shell ions via an electronically excited state has been reported [12,[16][17][18]. The energy barrier of the homolytic reaction has been estimated by frequency analysis of the transient structure with an electronic excitation energy of~0 eV along the potential energy scanning curve [12,16].…”