5 research outputs found
Direct Comparison of Solution and Gas-Phase Reactions of the Three Distonic Isomers of the Pyridine Radical Cation with Methanol
To directly compare the reactivity of positively charged
carbon-centered
aromatic Ď-radicals toward methanol in solution and in the gas
phase, the 2-, 3-, and 4-dehydropyridinium cations (distonic isomers
of the pyridine radical cation) were generated by ultraviolet photolysis
of the corresponding iodo precursors in a mixture of water and methanol
at varying pH. The reaction mixtures were analyzed by using liquid
chromatography/mass spectrometry. Hydrogen atom abstraction was the
only reaction observed for the 3- and 4-dehydropyridinium cations
(and pyridines) in solution. This also was the major reaction observed
earlier in the gas phase. Depending on the pH, the hydrogen atom can
be abstracted from different molecules (i.e., methanol or water) and
from different sites (in methanol) by the 3- and 4-dehydropyridinium
cations/pyridines in solution. In the pH range 1â4, the methyl
group of methanol is the main hydrogen atom donor site for both 3-
and 4-dehydropyridinium cations (just like in the gas phase). At higher
pH, the hydroxyl groups of water and methanol also act as hydrogen
atom donors. This finding is rationalized by a greater abundance of
the unprotonated radicals that preferentially abstract hydrogen atoms
from the polar hydroxyl groups. The percentage yield of hydrogen atom
abstraction by these radicals was found to increase with lowering
the pH in the pH range 1.0â3.2. This pH effect is rationalized
by polar effects: the lower the pH, the greater the fraction of protonated
(more polar) radicals in the solution. This finding is consistent
with previous results obtained in the gas phase and suggests that
gas-phase studies can be used to predict solution reactivity, but
only as long as the same reactive species is studied in both experiments.
This was found not to be the case for the 2-iodopyridinium cation.
Photolysis of this precursor in solution resulted in the formation
of two major addition products, 2-hydroxy- and 2-methoxypyridinium
cations, in addition to the hydrogen atom abstraction product. These
addition products were not observed in the earlier gas-phase studies
on 2-dehydropyridinium cation. Their observation in solution is explained
by the formation of another reactive intermediate, the 2-pyridyl cation,
upon photolysis of 2-iodopyridinium cation (and 2-iodopyridine). The
same intermediate was observed in the gas phase but it was removed
before examining the reactions of the desired radical, 2-dehydropyridinium
cation (which cannot be done in solution)
Reactivity of a Ď,Ď,Ď,Ď-Tetraradical: The 2,4,6-Tridehydropyridine Radical Cation
The 2,4,6-tridehydropyridine radical cation, an analogue
of the
elusive 1,2,3,5-tetradehydrobenzene, was generated in the gas phase
and its reactivity examined. Surprisingly, the tetraradical was found
not to undergo radical reactions. This behavior is rationalized by
resonance structures hindering fast radical reactions. This makes
the cation highly electrophilic, and it rapidly reacts with many nucleophiles
by quenching the NâC <i>ortho</i>-benzyne moiety,
thereby generating a relatively unreactive <i>meta</i>-benzyne
analogue
Substituent Effects on the Nonradical Reactivity of 4-Dehydropyridinium Cation
Recent studies have shown that the reactivity of the
4-dehydropyridinium
cation significantly differs from the reactivities of its isomers
toward tetrahydrofuran. While only hydrogen atom abstraction was observed
for the 2- and 3-dehydropyridinium cations, nonradical reactions were
observed for the 4-isomer. In order to learn more about these reactions,
the gas-phase reactivities of the 4-dehydropyridinium cation and several
of its derivatives toward tetrahydrofuran were investigated in a Fourier
transform ion electron resonance mass spectrometer. Both radical and nonradical
reactions were observed for most of these positively charged radicals.
The major parameter determining whether nonradical reactions occur
was found to be the electron affinity of the radicalsî¸only
those with relatively high electron affinities underwent nonradical
reactions. The reactivities of the monoradicals are also affected
by hydrogen bonding and steric effects
Identification of <i>N</i>âOxide and Sulfoxide Functionalities in Protonated Drug Metabolites by Using IonâMolecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer
The <i>in vivo</i> oxidation of sulfur and nitrogen atoms
in many drugs into sulfoxide and <i>N</i>-oxide functionalities
is a common biotransformation process. Unfortunately, the unambiguous
identification of these metabolites can be challenging. In the present
study, ionâmolecule reactions of trisÂ(diÂmethylÂamino)Âborane
followed by collisionally activated dissociation (CAD) in an ion trap
mass spectrometer are demonstrated to allow the identification of <i>N-</i>oxide and sulfoxide functionalities in protonated polyfunctional
drug metabolites. Only ions with <i>N</i>-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 â
DMA) and B fragment ions (M â HOâBÂ(NÂ(CH<sub>3</sub>)<sub>2</sub>)<sub>2</sub>) for <i>N-</i>oxides, but sulfoxides
also formed diagnostic C ions (M â OîťBNÂ(CH<sub>3</sub>)<sub>2</sub>), thus allowing differentiation of the functionalities.
Some protonated analytes yielded abundant TDMAB adducts that had lost <i>two</i> DMA molecules instead of just one. This provides information
on the environment of the <i>N</i>-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
(â)ESI/CAD MS<sup><i>n</i></sup> Procedure for Sequencing Lignin Oligomers Based on a Study of Synthetic Model Compounds with βâOâ4 and 5â5 Linkages
Seven
synthesized G-lignin oligomer model compounds (ranging in
size from dimers to an octamer) with 5-5 and/or β-O-4 linkages,
and three synthesized S-lignin model compounds (a dimer, trimer, and
tetramer) with β-O-4 linkages, were evaporated and deprotonated
using negative-ion mode ESI in a linear quadrupole ion trap/Fourier
transform ion cyclotron resonance mass spectrometer. The collision-activated
dissociation (CAD) fragmentation patterns (obtained in MS<sup>2</sup> and MS<sup>3</sup> experiments, respectively) for the negative ions
were studied to develop a procedure for sequencing unknown lignin
oligomers. On the basis of the observed fragmentation patterns, the
measured elemental compositions of the most abundant fragment ions,
and quantum chemical calculations, the most important reaction pathways
and likely mechanisms were delineated. Many of these reactions occur
via charge-remote fragmentation mechanisms. Deprotonated compounds
with only β-O-4 linkages, or both 5-5 and β-O-4 linkages,
showed major 1,2-eliminations of neutral compounds containing one,
two, or three aromatic rings. The most likely mechanisms for these
reactions are charge-remote Maccoll and retro-ene eliminations resulting
in the cleavage of a β-O-4 linkage. Facile losses of H<sub>2</sub>O and CH<sub>2</sub>O were also observed for all deprotonated model
compounds, which involve a previously published charge-driven mechanism.
Characteristic âion groupsâ and âkey ionsâ
were identified that, when combined with their CAD products (MS<sup>3</sup> experiments), can be used to sequence unknown oligomers