Enantioselectivity Effects in Clinical Metabolomics and Lipidomics

Abstract

Metabolomics and lipidomics have demonstrated increasing importance in underlying biochemical mechanisms involved in the pathogenesis of diseases to identify novel drug targets and/or biomarkers for establishing therapeutic approaches for human health. Particularly, bioactive metabolites and lipids have biological activity and have been implicated in various biological processes in physiological conditions. Thus, comprehensive metabolites, and lipids profiling are required to obtain further advances in understanding pathophysiological changes that occur in cells and tissues. Chirality is one of the most important phenomena in living organisms and has attracted long-term interest in medical and natural science. Enantioselective separation plays a pivotal role in understanding the distribution and physiological function of a diversity of chiral bioactive molecules. In this context, it has been the goal of method development for targeted and untargeted metabolomics and lipidomic assays. Herein we will highlight the benefits and challenges involved in these stereoselective analyses for clinical samples.

Quinine as a highly responsive chiral sensor for the 1H and 19F NMR enantiodiscrimination of N-trifluoroacetyl amino acids with free carboxyl functions

“…Dilution data for chiral substrates 4-7 and 9 in C 6 D 6 confirmed the trend found for 3, with differentiation of enantiomer signals in 1 H and/or 19 F spectra, which were suitable for quantitative determinations even at 5 mM (Table 2). Dilution until 5 mM in CDCl 3 led to enantioresolution quotients that were less than 1 and, hence, of no use for quantification.…”

“…The gHMBC (gradient heteronuclear multiple bond correlation) experiments were optimized for a long-range coupling constant of 8 Hz. Pure shift 1 H NMR spectra were recorded by using a PS1D sequence pre-installed with VNMRJ 4.2A with a relaxation delay of 2 s, an RSNOB selective 180°pulse of duration 15.4 ms, bandwidth 120 Hz under a slice-selection gradient Gsl of 1.5 G cm −1 , and a pure shift tau delay of 14.9 ms. 1 H NMR and 13 C NMR characterization data, reported in the ESI, † refer to numbered protons/carbons of chemical structures reported in the corresponding Fig. S3 and S8.…”

“…Chirality pervades pharmaceutical and biomedical areas [1][2][3][4] to such an extent that the detection and quantification of enantiomeric compounds constitute the focus of dedicated research areas, leading to the development of efficient, reliable and reproducible methods for enantiomer differentiation, among which chiral chromatography [5][6][7][8][9][10][11] and nuclear magnetic resonance (NMR) spectroscopy [12][13][14][15][16][17][18][19] emerge in terms of popularity. Both of them are grounded in the use of suitable chiral selectors able to make enantiomers distinguishable by transferring them into a diastereomeric environment.…”

“…1) seemed greatly advantageous: the derivatization procedure is very simple 40 and a fluorinated probe is introduced, thus opening the way to the detection of enantiomeric substrates in 19 F NMR spectra, where CSA signals cannot originate spectral interference. Two goals have also been pursued: the possibility to operate in substoichiometric amounts of the CSA, which could be beneficial in 1 H NMR enantiodiscrimination experiments, in order to limit spectral interference from the CSA, and, importantly, exploiting the presence of the fluorinated probe in the amino acid derivatives for the simultaneous detection, enantiodiscrimination and quantification of mixtures of amino acid derivatives in the 19 F NMR spectra. The choice of solvent represents a critical point for obtaining an efficient enantiodiscrimination since it could compete with the CSA in the interaction with the two enantiomeric substrates, thus undermining enantiomer differentiation.…”

Factors affecting variability in free oxylipins in mammalian tissues

“…Further limiting oxylipin analysis is the limited resolution of isomers and chiral separation of enantiomeric compounds from complex mixtures of stereoisomers. As reviewed by Oliveira [32], the field is in a continuous search for improvements to these methodologies.…”