Version 2 2024-01-09, 09:03Version 2 2024-01-09, 09:03
Version 1 2023-12-18, 23:29Version 1 2023-12-18, 23:29
journal contribution
posted on 2024-01-09, 09:03authored byLars T. Kuhn, Stefan Weber, Joachim Bargon, Teodor Parella, Míriam Pérez-Trujillo
The
direct and unambiguous detection and identification of individual
metabolite molecules present in complex biological mixtures constitute
a major challenge in (bio)analytical research. In this context, nuclear
magnetic resonance (NMR) spectroscopy has proven to be particularly
powerful owing to its ability to provide both qualitative and quantitative
atomic-level information on multiple analytes simultaneously in a
noninvasive manner. Nevertheless, NMR suffers from a low inherent
sensitivity and, moreover, lacks selectivity regarding the number
of individual analytes to be studied in a mixture of a myriad of structurally
and chemically very different molecules, e.g., metabolites in a biofluid.
Here, we describe a method that circumvents these shortcomings via
performing selective, photochemically induced dynamic nuclear polarization
(photo-CIDNP) enhanced NMR spectroscopy on unmodified complex biological
mixtures, i.e., human urine and serum, which yields a single, background-free
one-dimensional NMR spectrum. In doing this, we demonstrate that photo-CIDNP
experiments on unmodified complex mixtures of biological origin are
feasible, can be performed straightforwardly in the native aqueous
medium at physiological metabolite concentrations, and act as a spectral
filter, facilitating the analysis of NMR spectra of complex biofluids.
Due to its noninvasive nature, the method is fully compatible with
state-of-the-art metabolomic protocols providing direct spectroscopic
information on a small, carefully selected subset of clinically relevant
metabolites. We anticipate that this approach, which, in addition,
can be combined with existing high-throughput/high-sensitivity NMR
methodology, holds great promise for further in-depth studies and
development for use in metabolomics and many other areas of analytical
research.