Search Results (9)

Nuclear magnetic resonance (NMR) spectroscopy is gaining prominence as a vital quantitative method for sample analysis, with significant progress being made in the investigation of heteronuclei like phosphorus, a key element in numerous physiological functions. This paper provides a comprehensive review of the principles, methodologies, and applications of quantitative ³¹P nuclear magnetic resonance (qNMR) spectroscopy. It begins with an introduction to the fundamental principles of NMR spectroscopy, highlighting the specific advantages of qNMR and the unique properties of the ³¹P nucleus, including its high natural abundance and broad chemical shift range. While ¹H qNMR is widely used, signal overlap in complex mixtures can limit its accuracy. Additionally, this work explores diverse applications of ³¹P qNMR across fields such as food analysis, pharmaceuticals, and biology, emphasizing its contributions to real-time drug quantification, metabolomics, and environmental analysis. A key advantage of ³¹P NMR is its ability to provide exclusive detection and direct quantification of phosphorus in phosphorus-containing compounds. The internal standard method is favored for its simplicity, as it avoids the need for calibration curves, while the external standard method is better suited for natural products with established reference materials. This review aims to consolidate the applied prospects of ³¹P qNMR, emphasizing its potential to expand the horizons of quantitative detection technologies and facilitate advancements in future research and practical applications. Full article

Radio amplification using stimulated emission of radiation (RASER) effects in the NMR can increase NMR signals over time due to a feedback loop between the sample magnetization and the probe coil coupled with radiation damping (RD). Previously, RD rates had been directly observed only for the ¹H, ³He, ¹⁷O and ¹²⁹Xe nuclei. We report that experimental direct measurements of an NMR RASER to determine RD time constants for the three heteronuclei (¹³³Cs (I = 7/2), ⁷Li (I = 3/2) and ³¹P (I = 1/2)) in a highly concentrated solution from the NMR RASER emissions using a conventional NMR probe. Under conditions where the RD rate exceeds the transverse relaxation rate (i.e., the NMR RASER condition is fulfilled), we recorded both the transverse NMR RASER response to imperfect inversion and the recovery of longitudinal magnetization. The data were directly evaluated based on the well-known Bloom model as estimated RD rate constants of 8.0, 1.8 and 25 Hz for ¹³³Cs, ⁷Li and ³¹P, respectively. The proposed method can be applied to observe RD rate constants for the other nuclei as well. Full article

With sensitivity being the Achilles’ heel of nuclear magnetic resonance (NMR), the superior mass sensitivity offered by micro-coils can be an excellent choice for tiny, mass limited samples such as eggs and small organisms. Recently, complementary metal oxide semiconductor (CMOS)-based micro-coil transceivers have been reported and demonstrate excellent mass sensitivity. However, the ability of broadband CMOS micro-coils to study heteronuclei has yet to be investigated, and here their potential is explored within the lens of environmental research. Eleven nuclei including ⁷Li, ¹⁹F, ³¹P and, ²⁰⁵Tl were studied and detection limits in the low to mid picomole range were found for an extended experiment. Further, two environmentally relevant samples (a sprouting broccoli seed and a D. magna egg) were successfully studied using the CMOS micro-coil system. ¹³C NMR was used to help resolve broad signals in the ¹H spectrum of the ¹³C enriched broccoli seed, and steady state free precession was used to improve the signal-to-noise ratio by a factor of six. ¹⁹F NMR was used to track fluorinated contaminants in a single D. magna egg, showing potential for studying egg–pollutant interactions. Overall, CMOS micro-coil NMR demonstrates significant promise in environmental research, especially when the future potential to scale to multiple coil arrays (greatly improving throughput) is considered. Full article

Efficient ¹³C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-¹³C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CD₃OD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the ¹³C nucleus of transiently bound ketoisocaproate. ¹³C polarization values of up to 18% are achieved at the 1-¹³C site in 1 min in the liquid state at 30 mM substrate concentration. The efficient polarization build-up becomes possible due to favorable relaxation dynamics. Specifically, the exponential build-up time constant (14.3 ± 0.6 s) is substantially lower than the corresponding polarization decay time constant (22.8 ± 1.2 s) at the optimum polarization transfer field (0.4 microtesla) and temperature (10 °C). The experiments with natural abundance ketoisocaproate revealed polarization level on the ¹³C-2 site of less than 1%—i.e., one order of magnitude lower than that of the 1-¹³C site—which is only partially due to more-efficient relaxation dynamics in sub-microtesla fields. We rationalize the overall much lower ¹³C-2 polarization efficiency in part by less favorable catalyst-binding dynamics of the C-2 site. Pilot SABRE experiments at pH 4.0 (acidified sample) versus pH 6.1 (unaltered sodium [1-¹³C]ketoisocaproate) reveal substantial modulation of SABRE-SHEATH processes by pH, warranting future systematic pH titration studies of ketoisocaproate, as well as other structurally similar ketocarboxylate motifs including pyruvate and alpha-ketoglutarate, with the overarching goal of maximizing ¹³C polarization levels in these potent molecular probes. Finally, we also report on the pilot post-mortem use of HP [1-¹³C]ketoisocaproate in a euthanized mouse, demonstrating that SABRE-hyperpolarized ¹³C contrast agents hold promise for future metabolic studies. Full article

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. Full article

This is a broad overview and critical review of a particular group of closely related ex vivo and in vitro metabolic NMR spectroscopic methods. The scope of interest comprises studies of cultured cells and excised tissue, either intact or after physicochemical extraction of metabolites. Our detailed discussion includes pitfalls that have led to erroneous statements in the published literature, some of which may cause serious problems in metabolic and biological interpretation of results. To cover a wide range of work from relevant research areas, we consider not only the most recent achievements in the field, but also techniques that proved to be valid and successful in the past, although they may not have generated a very significant number of papers more recently. Thus, this comparative review also aims at providing background information useful for judiciously choosing between the metabolic ex vivo/in vitro NMR methods presented. Finally, the methods of interest are discussed in the context of, and in relation to, other metabolic analysis protocols such as HR-MAS and cell perfusion NMR, as well as the mass spectrometry approach. Full article

It is well known that the association of parahydrogen (pH₂) with an unsaturated molecule or a transient metalorganic complex can enhance the intensity of NMR signals; the effect is known as parahydrogen-induced polarization (PHIP). During recent decades, numerous methods were proposed for converting pH₂-derived nuclear spin order to the observable magnetization of protons or other nuclei of interest, usually ¹³C or ¹⁵N. Here, we analyze the constraints imposed by the topological symmetry of the spin systems on the amplitude of transferred polarization. We find that in asymmetric systems, heteronuclei can be polarized to 100%. However, the amplitude drops to 75% in A₂BX systems and further to 50% in A₃B₂X systems. The latter case is of primary importance for biological applications of PHIP using sidearm hydrogenation (PHIP-SAH). If the polarization is transferred to the same type of nuclei, i.e., ¹H, symmetry constraints impose significant boundaries on the spin-order distribution. For AB, A₂B, A₃B, A₂B₂, AA’(AA’) systems, the maximum average polarization for each spin is 100%, 50%, 33.3%, 25%, and 0, respectively, (where A and B (or A’) came from pH₂). Remarkably, if the polarization of all spins in a molecule is summed up, the total polarization grows asymptotically with ~1.27$\sqrt{N}$ and can exceed 2 in the absence of symmetry constraints (where $N$ is the number of spins). We also discuss the effect of dipole–dipole-induced pH₂ spin-order distribution in heterogeneous catalysis or nematic liquid crystals. Practical examples from the literature illustrate our theoretical analysis. Full article

In the past decades, nanosized drug delivery systems (DDS) have been extensively developed and studied as a promising way to improve the performance of a drug and reduce its undesirable side effects. DDSs are usually very complex supramolecular assemblies made of a core that contains the active substance(s) and ensures a controlled release, which is surrounded by a corona that stabilizes the particles and ensures the delivery to the targeted cells. To optimize the design of engineered DDSs, it is essential to gain a comprehensive understanding of these core–shell assemblies at the atomic level. In this review, we illustrate how solid-state nuclear magnetic resonance (ssNMR) spectroscopy has become an essential tool in DDS design. Full article

The successful applications of magnetic resonance imaging (MRI) in medicine are mostly due to the non-invasive and non-destructive nature of MRI techniques. Longitudinal studies of humans and animals are easily accomplished, taking advantage of the fact that MRI does not use harmful radiation that would be needed for plain film radiographic, computerized tomography (CT) or positron emission (PET) scans. Routine anatomic and functional studies using the strong signal from the most abundant magnetic nucleus, the proton, can also provide metabolic information when combined with in vivo magnetic resonance spectroscopy (MRS). MRS can be performed using either protons or hetero-nuclei (meaning any magnetic nuclei other than protons or 1H) including carbon (13C) or phosphorus (31P). In vivo MR spectra can be obtained from single region ofinterest (ROI or voxel) or multiple ROIs simultaneously using the technique typically called chemical shift imaging (CSI). Here we report applications of CSI to marine samples and describe a technique to study in vivo glycine metabolism in oysters using 13C MRS 12 h after immersion in a sea water chamber dosed with [2-13C]-glycine. This is the first report of 13C CSI in a marine organism. Full article