2 research outputs found
Enantioselective Reduction of Noncovalent Complexes of Amino Acids with Cu<sup>II</sup> via Resonant Collision-Induced Dissociation: Collision Energy, Activation Duration Effects, and RRKM Modeling
Formation of noncovalent complexes is one of the approaches
to
perform chiral analysis with mass spectrometry. Enantiomeric distinction
of amino acids (AAs) based on the relative rate constants of competitive
fragmentations of quaternary copper complexes is an efficient method
for chiral differentiation. Here, we studied the complex [CuII,(Phe,PhG,Pro-H)]+ (m/z 493) under resonant collision-induced dissociation conditions while
varying the activation time. The precursor ion can yield two main
fragments through the loss of the non-natural AA phenylglycine (PhG):
the expected product ion [CuII,(Phe,Pro-H)]+ (m/z 342) and the reduced product
ion [CuI,(Phe,Pro)]+ (m/z 343). Enantioselective reduction describes the difference
in relative abundance of these ions, which depends on the chirality
of the precursor ion: the formation of the reduced ion m/z 343 is favored in homochiral complexes (DDD)
compared to heterochiral complexes (such as LDD). Energy-resolved
mass spectrometry data show that reduction, which arises from rearrangement,
is favored at a low collision energy (CE) and long activation time
(ActT), whereas direct cleavage preferentially occurs at a high CE
and short ActT. These results were confirmed with kinetic modeling
based on RRKM theory. For this modeling, it was necessary to set a
pre-exponential factor as a reference, so that the E0 values obtained are relative values. Interestingly,
these simulations showed that the critical energy E0 required to form the reduced ion is comparable in both
homochiral and heterochiral complexes. However, the formation of
product ion m/z 342 through direct
cleavage is associated with a lower E0 in heterochiral complexes. Consequently, enantioselectivity would
not be caused by enhanced reduction in homochiral complexes but rather
by direct cleavage being favored in heterochiral complexes
Chemical Exposure Highlighted without Any <i>A Priori</i> Information in an Epidemiological Study by Metabolomic FT-ICR-MS Fingerprinting at High Throughput and High Resolution
Epidemiological studies aim to assess associations between
diseases
and risk factors. Such investigations involve a large sample size
and require powerful analytical methods to measure the effects of
risk factors, resulting in a long analysis time. In this study, chemical
exposure markers were detected as the main variables strongly affecting
two components coming from a principal component analysis (PCA) exploration
of the metabolomic data generated from urinary samples collected on
a cohort of about 500 individuals using direct introduction coupled
with a Fourier-transform ion cyclotron resonance instrument. The assignment
of their chemical identity was first achieved based on their isotopic
fine structures detected at very high resolution (Rp > 900,000). Their identification as dimethylbiguanide
and sotalol was obtained at level 1, thanks to the available authentic
chemical standards, tandem mass spectrometry (MS/MS) experiments,
and collision cross section measurements. Epidemiological data confirmed
that the subjects discriminated by PCA had declared to be prescribed
these drugs for either type II diabetes or cardiac arrhythmia. Concentrations
of these drugs in urine samples of interest were also estimated by
rapid quantification using an external standard calibration method,
direct introduction, and MS/MS experiments. Regression analyses showed
a good correlation between the estimated drug concentrations and the
scores of individuals distributed on these specific PCs. The detection
of these chemical exposure markers proved the potential of the proposed
high-throughput approach without any prior drug exposure knowledge
as a powerful emerging tool for rapid and large-scale phenotyping
of subjects enrolled in epidemiological studies to rapidly characterize
the chemical exposome and adherence to medical prescriptions