Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives

Ausmees, Kerti; Reimets, Nele; Reile, Indrek

doi:10.3390/molecules27030802

Cited by 8 publications

(9 citation statements)

References 37 publications

(93 reference statements)

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“…Given that the detection of nucleobase-containing biomarkers of disease have opened new areas of research, there should be natural interest in the investigation of rapid and inexpensive parahydrogen-based methods for hyperpolarizing nucleobases and their use in potential applications; however, to date there have only been a few such studies reported. In one type of approach, the unique resonances of catalyst-bound hyperpolarized hydrides [ 48 , 49 , 50 ] are used to detect the presence of specific nucleobases (and their tautomers) with high sensitivity, including in complex biological media [ 51 , 52 ]. Hövener et al reported 1 H hyperpolarization of adenine and adenosine as part of efforts to demonstrate continuous polarization in MRI applications [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange

et al. 2023

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The present work investigates the potential for enhancing the NMR signals of DNA nucleobases by parahydrogen-based hyperpolarization. Signal amplification by reversible exchange (SABRE) and SABRE in Shield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) of selected DNA nucleobases is demonstrated with the enhancement (ε) of 1H, 15N, and/or 13C spins in 3-methyladenine, cytosine, and 6-O-guanine. Solutions of the standard SABRE homogenous catalyst Ir(1,5-cyclooctadeine)(1,3-bis(2,4,6-trimethylphenyl)imidazolium)Cl (“IrIMes”) and a given nucleobase in deuterated ethanol/water solutions yielded low 1H ε values (≤10), likely reflecting weak catalyst binding. However, we achieved natural-abundance enhancement of 15N signals for 3-methyladenine of ~3300 and ~1900 for the imidazole ring nitrogen atoms. 1H and 15N 3-methyladenine studies revealed that methylation of adenine affords preferential binding of the imidazole ring over the pyrimidine ring. Interestingly, signal enhancements (ε~240) of both 15N atoms for doubly labelled cytosine reveal the preferential binding of specific tautomer(s), thus giving insight into the matching of polarization-transfer and tautomerization time scales. 13C enhancements of up to nearly 50-fold were also obtained for this cytosine isotopomer. These efforts may enable the future investigation of processes underlying cellular function and/or dysfunction, including how DNA nucleobase tautomerization influences mismatching in base-pairing.

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Section: Introductionmentioning

confidence: 99%

Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange

et al. 2023

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“…3 Additional nhPHIP studies in the chemical analysis of urine have also recently been reported. 51,52 3.2.4. Enhanced Dispersion of Signals by the Zero-(ZQ) Approach.…”

Section: Analysis Of Aqueous Mixtures With Solid-phasementioning

confidence: 99%

“… 3 Additional nhPHIP studies in the chemical analysis of urine have also recently been reported. 51 , 52 …”

Section: Applications Of Sabre/nhphip At Low Concentrationsmentioning

confidence: 99%

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Analysis of Complex Mixtures by Chemosensing NMR Using para-Hydrogen-Induced Hyperpolarization

Fraser¹,

Rutjes²,

Feiters³

et al. 2022

Acc. Chem. Res.

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Conspectus Nuclear magnetic resonance (NMR) is a powerful technique for chemical analysis. The use of NMR to investigate dilute analytes in complex systems is, however, hampered by its relatively low sensitivity. An additional obstacle is represented by the NMR signal overlap. Because solutes in a complex mixture are usually not isotopically labeled, NMR studies are often limited to 1 H measurements, which, because of the modest dispersion of the 1 H resonances (typically ∼10 ppm), can result in challenging signal crowding. The low NMR sensitivity issue can be alleviated by nuclear spin hyperpolarization (i.e., transiently increasing the differences in nuclear spin populations), which determines large NMR signal enhancements. This has been demonstrated for hyperpolarization methods such as dynamic nuclear polarization, spin-exchange optical pumping and para -hydrogen-induced polarization (PHIP). In particular, PHIP has grown into a fast, efficient, and versatile technique since the recent discovery of non-hydrogenative routes to achieve nuclear spin hyperpolarization. For instance, signal amplification by reversible exchange (SABRE) can generate proton as well as heteronuclear spin hyperpolarization in a few seconds in compounds that are able to transiently bind to an iridium catalyst in the presence of para -hydrogen in solution. The hyperpolarization transfer catalyst acts as a chemosensor in the sense that it is selective for analytes that can coordinate to the metal center, such as nitrogen-containing aromatic heterocycles, sulfur heteroaromatic compounds, nitriles, Schiff bases, diaziridines, carboxylic acids, and amines. We have demonstrated that the signal enhancement achieved by SABRE allows rapid NMR detection and quantification of a mixture of substrates down to low-micromolar concentration. Furthermore, in the transient complex, the spin configuration of p -H 2 can be easily converted to spin hyperpolarization to produce up to 1000-fold enhanced NMR hydride signals. Because the hydrides’ chemical shifts are highly sensitive to the structure of the analyte associating with the iridium complex, they can be employed as hyperpolarized “probes” to signal the presence of specific compounds in the mixture. This indirect detection of the analytes in solution provides important benefits in the case of complex systems, as hydrides resonate in a region of the 1 H spectrum (at ca. −20 ppm) that is generally signal-free. The enhanced sensitivity provided by non-hydrogenative PHIP (nhPHIP), together with the absence of interference from the complex matrix (usually resonating between 0 and 10 ppm), set the detection limit for this NMR chemosensor down to sub-μM concentrations, approximately 3 orders of magnitude lower than for conventional NMR. This nhPHIP approach represents, therefore, a powerful tool for NMR analysis of dilut...

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“…[67][68][69] Moreover, parahydrogen hyperpolarization has also demonstrated a strong potential in biomedicine, [70] for the study, for instance, of urine samples. [71][72][73][74] There is still a long way to go to implement these techniques in pure shift experiment, but they have raised great expectations for improved sensitivity that will be essential in the future to achieve the detection of a greater number of metabolic pathways and address a larger number of biological questions.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Present and future of pure shift NMR in metabolomics

Chen

Bertho

Caradeuc

et al. 2023

Magnetic Reson in Chemistry

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NMR is one of the most powerful techniques for the analysis of biological samples in the field of metabolomics. However, the high complexity of fluids, tissues, or other biological materials taken from living organisms is still a challenge for state‐of‐the‐art pulse sequences, thereby limiting the detection, the identification, and the quantification of metabolites. In this context, the resolution enhancement provided by broadband homonuclear decoupling methods, which allows for simplifying 1H multiplet patterns into singlets, has placed this so‐called pure shift technique as a promising approach to perform metabolic profiling with unparalleled level of detail. In recent years, the many advances achieved in the design of pure shift experiments has paved the way to the analysis of a wide range of biological samples with ultra‐high resolution. This review leads the reader from the early days of the main pure shift methods that have been successfully developed over the last decades to address complex samples, to the most recent and promising applications of pure shift NMR to the field of NMR‐based metabolomics.

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Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives

Cited by 8 publications

References 37 publications

Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange

Hyperpolarizing DNA Nucleobases via NMR Signal Amplification by Reversible Exchange

Analysis of Complex Mixtures by Chemosensing NMR Using para-Hydrogen-Induced Hyperpolarization

Present and future of pure shift NMR in metabolomics

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