arXiv subjects

Andrey N. Pravdivtsev

Publications and source records attributed to Andrey N. Pravdivtsev.

16 recordsLinked to original sources

arXiv2026

Mechanistic Insights into Chemical Exchange during the Signal Amplification by Reversible Exchange Sensitization of Pyruvate

Signal amplification by reversible exchange (SABRE) is a nuclear spin hyperpolarization technique in which the transient interaction of parahydrogen (pH2) and a target substrate with an iridium complex leads to polarization transfer to the substrate. Here, we use a parahydrogen-enhanced, spin-selective NMR method to investigate pyruvate binding, which is combined with exchange-model fitting and DFT calculations. Our study reveals several key findings that reshape the current understanding of SABRE: (a) intramolecular hydrogen exchange of the hydrides, occurring faster than pyruvate or H2 loss; (b) the discovery of a novel stable [Ir(H)2(IMes)(\k{appa}1-pyr)(DMSO)2] complex; and (c) the potential role of counterions (here Na+) in Ir-pyruvate binding. Previously unknown insights into complex kinetics and distributions as a function of temperature, [DMSO], [pyruvate], and hydrogen pressure are presented. The methods demonstrated here, exemplified by SABRE, provide a framework that is expected to guide future research in the field.

physics.chem-ph↗

arXiv2025

Over four minutes relaxation of pyruvate using chemically and physically induced deceleration of relaxation

[1-13C]pyruvate is the most widely used tracer for hyperpolarized metabolic magnetic resonance imaging, with profound applications in tumor and inflammation diagnosis as well as treatment monitoring. The most fundamental hurdle to broader application, however, remains the rapid polarization relaxation and the associated signal loss. Here, we report a method to address this challenge. Studying the nuclear spin relaxation dispersion of [1-13C]pyruvate across magnetic fields from 8 μT to 9.4 T, as a function of additives, solvents, and preparation methods, allowed us to achieve relaxation times of up to four minutes. Such a long time could enable reliable quality control and nearly polarization loss-free transport, further boosting the power of hyperpolarized metabolic MRI.

physics.chem-ph↗

arXiv2025

Upscaling the hyperpolarization sample volume of an automated hydrogenative parahydrogen-induced polarizer

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) suffer from inherently low sensitivity due to the weak thermal polarization of nuclear spins. Parahydrogen-induced polarization (PHIP) offers a powerful route to enhance NMR signals by several orders of magnitude, enabling real-time metabolic imaging. However, PHIP implementations are often constrained by small sample volumes, limited automation, and complex high-pressure requirements. In this work, we present an upgraded, automated PHIP system capable of hyperpolarizing sample volumes of up to 2.2 mL, making it suitable for preclinical MRI applications. We developed several high-pressure reactors and multi-port NMR tube caps compatible with standard commercial 5, 10, and 16 mm glass tubes. Reactor designs were simulated and fabricated from chemically resistant polymers, ensuring mechanical safety at more than 30 bar. Using FLASH MRI, nutation, and CPMG sequences, we characterized magnetic field homogeneity and stability, establishing optimal sample dimensions (12.5/16 mm ID/OD glass tube, 20 mm height) with B0 inhomogeneity below 2.5 ppm and B1 inhomogeneity around 1%. A high level of injection reproducibility was confirmed (volume precision ~0.6%). Optimization of experimental parameters, including hydrogenation pressure, pH2 flow rate, and sample temperature, enabled rapid and efficient polarization transfer. At optimized conditions (20 bar pH2, 2 L/min flow, 55°C, 4 s bubbling time), up to 31.3% 1H polarization of two protons was achieved for deuterated ethyl acetate in acetone with the theoretical maximum of 50%. This level of polarization was achieved with a duty cycle of 80 s, and the standard deviation of the mean was below 6.8%.

physics.ins-det↗

arXiv2025

Compact magnetic field cycling system with the range from nT to 9.4 T exemplified with 13C relaxation dispersion and SABRE-SHEATH hyperpolarization

We present a compact magnetic field cycling system for high-resolution NMR spectrometers. The system enables the transfer of the sample from B0 field of 9.4 T to about nT and all fields in between within 1 second. Utilizing a flexible gear rod made the shuttling system more compact, reducing the height to about the height required for filling liquid helium - hence, it can be installed in average-size NMR laboratories (the height of NMR with MFC is only 3.32 m). The system utility is exemplified by measuring T1 relaxation dispersion of the most common liquid state hyperpolarization tracer - [1-13C]pyruvate - and magnetic field dependences of signal amplification by reversible exchange enabling alignment transfer to heteronuclei (SABRE-SHEATH) hyperpolarization of [15N]pyridine. Using the system, we uncovered the exact relaxation of the pyruvate for a common preclinical dDNP sample composition and gave quantitative estimates for the retained polarization after sample transfer. We modified the observation protocol of SABRE-SHEATH polarization, which, with the high reproducibility of the MFC, provided us with a method to measure the chemical exchange rates of hyperpolarized compounds.

physics.chem-ph↗

arXiv2025

Maximizing NMR Sensitivity: A Guide to Receiver Gain Adjustment

Novel methods and technology drive the rapid advances of nuclear magnetic resonance (NMR). The primary objective of developing novel hardware is to improve sensitivity and reliability (and possibly to reduce cost). Automation has made NMR much more convenient, but it may lead to trusting the algorithms without regular checks. In this contribution, we analyzed the signal and signal-to-noise ratio (SNR) as a function of the receiver gain (RG) for 1H, 2H, 13C, and 15N nuclei on five spectrometers. On a 1 T benchtop spectrometer (Spinsolve, Magritek), the SNR showed the expected increase as a function of RG. Still, the 1H and 13C signal amplitudes deviated by up to 50% from supposedly RG-independent signal intensities. On 7, 9.4, 11.7, and 14.1 T spectrometers (Avance Neo, Bruker), the signal intensity increases linearly with RG as expected, but surprisingly a drastic drop of SNR is observed for some X-nuclei and fields. For example, while RG = 18 provided a 13C SNR similar to that at a maximum RG of 101 at 9.4 T, at RG = 20.2 the determined SNR was 32% lower. The SNR figures are strongly system and resonance frequency dependent. Our findings suggest that NMR users should test the specific spectrometer behavior to obtain optimum SNR for their experiments, as automatic RG adjustment does not account for the observed characteristics. In addition, we provide a method to estimate optimal settings for thermally and hyperpolarized samples of a chosen concentration, polarization, and flip angle, which provide a high SNR and avoid ADC-overflow artefacts.

physics.ins-det↗

arXiv2024

Characterization of Nuclear Magnetism at Ultralow and Zero Field using SQUIDs

Nuclear magnetism underpins areas such as medicine in magnetic resonance imaging (MRI). Hyperpolarization of nuclei enhances the quantity and quality of information that can be determined from these techniques by increasing their signal to noise ratios by orders of magnitude. However, some of these hyperpolarization techniques rely on the use of low to ultralow magnetic fields (ULF) (nTs-mTs). The broadband character and ultrasensitive field sensitivity of superconducting quantum interference devices (SQUID) allow for probing nuclear magnetism at these fields, where other magnetometers, such as Faraday coils and flux gates do not. To this end, we designed a reactor to hyperpolarize [1-$^{13}$C]pyruvate with the technique, signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). Hyperpolarized pyruvate has been shown to be very powerful for the diagnosis of tumours with MRI as its metabolism is associated with various pathologies. We were able to characterize the field sensitivity of our setup by simulating the filled reactor in relation to its placement in our ultralow noise, ULF MRI setup. Using the simulations, we determined that our hyperpolarization setup results in a $^{13}$C polarization of 0.4 %, a signal enhancement of $\sim$100~000~000 versus the predicted thermal equilibrium signal at earth field ($\sim$50 $μ$T). This results in a $^{13}$C signal of 6.20$\pm$0.34~pT, which with our ultralow noise setup, opens the possibility for direct observation of the hyperpolarization and the subsequent spin-lattice relaxation without system perturbation.

cond-mat.supr-con↗

arXiv2024

Indirect Zero Field NMR Spectroscopy

This study pioneers the two-field correlation spectroscopy (COSY) in zero to ultralow field (ZULF) liquid state NMR, employing hyperpolarized [1-$^{13}$C]pyruvate as a model system. We demonstrate the successful integration of signal amplification by reversible exchange (SABRE) for hyperpolarization, enabling the detection of ZULF COSY spectra with increased sensitivity. The use of field cycling allows the acquisition of two-field COSY spectra at varying magnetic field strengths, including zero-field conditions. This enables insight into both J-coupling and Zeeman-dominated regimes benefiting from ULF field observation sensitivity and mitigation of low-frequency noise by conducting readout at higher fields (>5 $μ$T). Our study explores the effects of polarization transfer, apodization techniques, and the potential for further application of ZULF NMR in chemical analysis exemplified for three X-nuclei and three corresponding molecules: [1-$^{13}$C]pyruvate, [$^{15}$N]acetonitrile and [3-$^{19}$F]pyridine. These findings pave the way for more sensitive and cost-effective NMR spectroscopy in low-field regimes.

physics.med-ph↗

arXiv2024

Diversity of Parahydrogen-Induced Hyperpolarization Effects in Chemistry

Nuclear spin hyperpolarization utilizing parahydrogen has the potential for broad applications in chemistry, biochemistry, and medicine. This review examines recent chemical and biochemical insights gained using parahydrogen-induced polarization (PHIP). We begin with photo-induced PHIP, which allows the investigation of short-lived and photo-activated catalysis. Next, we review the partially negative line effect, in which distinctive lineshape helps to reveal information about rapid exchange with parahydrogen and the role of short-lived catalytic species. The NMR signal enhancement of a single proton in oneH-PHIP is discussed, challenging the underpinning concept of the necessity of pairwise hydrogenation. Furthermore, we examine metal-free PHIP facilitated by novel molecular tweezers and radicaloids, demonstrating alternative routes to conventional hydrogenation using metal-based catalysts. Although symmetric molecules incorporating parahydrogen are NMR silent, we showcase methods that reveal hyperpolarized states through post-hydrogenation reactions. We discuss chemical exchange processes that mediate polarization transfer between parahydrogen and a molecular target, expanding the reach of PHIP without synthesizing specialized precursors. We conclude this review by highlighting the role of PHIP in uncovering the H2 activation mechanisms of hydrogenases. By providing a detailed review of these diverse phenomena, we aim to familiarize the reader with the versatility of PHIP and its potential applications for mechanistic studies and chemical analysis.

physics.chem-ph↗

arXiv2023

LIGHT-SABRE hyperpolarizes 1-^{13}C-pyruvate continuously, without magnetic field cycling

Nuclear spin hyperpolarization enables real-time observation of metabolism and intermolecular interactions in vivo. 1-13C-Pyruvate is the leading hyperpolarized tracer currently under evaluation in several clinical trials as a promising molecular imaging agent. Still, the quest for a simple, fast, and efficient hyperpolarization technique is ongoing. Here, we describe that continuous, weak irradiation in the audio-frequency range of the 13C spin at 121 μT magnetic field (\sim twiceEarth\apos s field) enables spin order transfer from parahydrogen to 13C magnetization of 1-13C-pyruvate. These so-called LIGHT-SABRE pulses couple nuclear spin states of parahydrogen and pyruvate via the J-coupling network of reversibly exchanging Ir-complexes. Using \sim 100% parahydrogen at ambient pressure, we polarized 51 mM of 1-13C-pyruvate in the presence of 5.1 mM Ir-complex continuously and repeatedly to a polarization of 1.1% averaged over free and catalyst-bound pyruvate. The experiments were conducted at -8°C), where almost exclusively bound pyruvate was observed, corresponding to an estimated 11% polarization on bound pyruvate. The obtained hyperpolarization levels closely match those obtained via SABRE-SHEATH under otherwise identical conditions. The creation of three different types of spin orders was observed: transverse 13C magnetization along the applied magnetic field, 13C z-magnetization along the main field B_0, and 13C-1H zz-spin-order. With a superconducting quantum interference device (SQUID) for detection, we found that the generated spin orders result from tiny 1H-13C J-coupling interactions, which are not visible even with our narrow linewidth below 0.3 Hz.

physics.chem-ph↗

arXiv2021

Symmetry constraints on spin order transfer in parahydrogen-induced polarization (PHIP)

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 the last decades, numerous methods were proposed for converting pH2-derived nuclear spin order to the observable magnetization of pro-tons 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. 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 maxi-mum average polarization for each spin is 100%, 50%, 33.3%, 25%, and 0, respectively, when A and B (or A') came from pH2 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.

physics.chem-ph↗

arXiv2021

Selectively pulsed spin order transfer increases parahydrogen-induced NMR amplification of insensitive nuclei and makes polarization transfer more robust

We describe a new method for pulsed spin order transfer (SOT) of parahydrogen induced polarization (PHIP) that enables close to 100 % polarization in incompletely 2H-labeled molecules by exciting only the desired protons in a frequency-selective manner. While a selective pulse (SP) on 1H at the beginning of pulsed SOT had been considered before, using SPs during the SOT suppresses undesired indirect spin-spin interactions. As a result, we achieved a more robust SOT for the SP variants of the phINEPT+ sequence that we refer to as phSPINEPT+. Thereby, for the first time, we report a sequence that is effective for all weakly coupled spin systems. Our simulations show that the method converts close to 100 % of the parahydrogen-derived spin order into 13C hyperpolarization in weakly coupled three-spin systems and partially or fully 2H-labeled molecules if relaxation is neglected. Experimentally we demonstrate high hyperpolarization of 13C with 15.8 % for 1-13C-hydroxyethyl propionate-d3 and 12.6 % for 1-13C-ethyl acetate-d6, which corresponds to ~47 % and ~38 % if the enrichment of parahydrogen had been 100 %. Even in non-2H-labeled molecules, a remarkable 13C polarization is achieved, e.g. up to 20 % were simulated for 100 % pH2, and 1.25 % were obtained experimentally for 1-13C-ethyl pyruvate and 50 % pH2, which can be further improved by faster hydrogenation. As a result, full deuterium labeling may no longer be required e.g., when new PHIP agents are investigated, the synthesis of fully deuterated molecules is too complex, or when a kinetic isotope effect regarding the metabolic conversion rate of an agent is to be avoided. Using SPs during SOT seems very promising and may be extended to other sequences in the context of PHIP and be-yond to make them less prone to experimental imperfections or real molecular environments.

physics.chem-ph↗

arXiv2021

Coherent evolution of signal amplification by reversible exchange in two alternating fields (alt-SABRE)

Parahydrogen (pH2) is a convenient and cost efficient source for magnetic resonance signal enhancement. Transient interaction of pH2 with a metal organic complex in a signal amplification by reversible exchange (SABRE) experiment enabled more than 10% polarization for some 15N molecules. Here, we analyzed a variant of SABRE, consisting of an outer magnetic field alternating between a low field of ~1 \muT, where a polarization transfer takes place, and a higher field >50 \muT (alt-SABRE). We found effects of both of these fields on amplitude and the frequency of polarization transfer. Deviation of a lower magnetic field from a "perfect" condition of level anti-crossing increases the frequency of polarization transfer that can be exploited for polarization of short-lived transient SABRE complexes i.e. some substrates. Moreover, the coherences responsible for polarization transfer at a lower field persisted during magnetic field variation and continued their spin evolution at higher field with a frequency of 2.5 kHz at 54 \muT. The latter should be taken into consideration for an efficient alt-SABRE.

physics.chem-ph↗

arXiv2020

Parahydrogen-induced polarization relayed via proton exchange

The sensitivity of NMR and MRI can be boosted via hyperpolarization of nuclear spins. However, current methods are costly, polarization is relatively low, or applicability is limited. Here, we report a new hyperpolarization method combining the low-cost, high polarization of hydrogenative parahydrogen-induced polarization (PHIP) with the flexibility of polarization transfer via proton exchange. The new method can be used to polarize various molecules, including alcohols, water, lactate, and pyruvate. On average, only $\approx$3 mM of a hyperpolarized transfer agent was sufficient to significantly enhance the signal of $\approx$100 mM of target molecules via proton exchange. Thus, hydrogenative parahydrogen-induced hyperpolarization with proton exchange (PHIP-X) provides a new avenue for NMR applications beyond the limits imposed by thermal polarization.

physics.chem-ph↗

arXiv2020

Singlet state encoded magnetic resonance (SISTEM) spectroscopy

Magnetic resonance spectroscopy (MRS) allows the analysis of biochemical processes non invasively and in vivo. Still, its application in clinical diagnostics is rare. Routine MRS is limited to spatial, chemical and temporal resolutions of cubic centimetres, mM and minutes. In fact, the signal of many metabolites is strong enough for detection, but the resonances significantly overlap, exacerbating identification and quantification. In addition, the signals of water and lipids are much stronger and dominate the entire spectrum. To suppress the background and isolate selected signals, usually, relaxation times, J-coupling and chemical shifts are used. Here, we propose methods to isolate the signals of selected molecular groups within endogenous metabolites by using long-lived spin states (LLS). We exemplify the method by preparing the LLSs of coupled protons in the endogenous molecules N-acetyl-L-aspartic acid (NAA). First, we store polarization in long-lived, double spin states and then apply saturation pulses and double quantum filters to suppress background signals. We show that LLS can be used to selectively prepare and measure the signals of chosen metabolites or drugs in the presence of water, inhomogeneous field and highly concentrated fatty solutions. The pH measurement presented here is one of the possible applications.

physics.chem-ph↗

arXiv2019

Continuous Radio Amplification by Stimulated Emission using Parahydrogen Induced Polarization (PHIP-RASER) at 14 Tesla

Nuclear Magnetic Resonance (NMR) is an intriguing quantum-mechanical effect that is used for daily life medical diagnostics and chemical analysis alike. Numerous advancements have contributed to the success of the technique, including hyperpolarized contrast agents that enables real-time imaging of metabolism in vivo. In physics, hyperpolarization has enabled an NMR RASER using a custom low-field setup and high-Q coils only recently. Expanding on this discovery, we report the finding of a RASER emitting 1H NMR signal continuously for more than 10 min at a high frequency of 600 MHz. Full chemical shift resolution is maintained and a linewidth of 2 ppb was achieved. A new simulation of a RASER effect in a coupled two spin-1/2 system was implemented and reproduced experimental findings. The effect was found using standard equipment only; no dedicated setup is necessary, making the NMR RASER accessible to a wide group of researchers.

physics.chem-ph↗

arXiv2016

Robust conversion of singlet spin order in coupled spin-1/2 pairs by adiabatically switched RF-fields

We propose a robust and highly efficient NMR technique to create singlet spin order from longitudinal spin magnetization in coupled spin-1/2 pairs and to perform backward conversion (singlet order)$\to$magnetization. In this method we exploit adiabatic switching of an RF-field in order to drive transitions between the singlet state and the $T_\pm$ triplet states of a spin pair under study. We demonstrate that the method works perfectly for both strongly and weakly coupled spin pairs, providing a conversion efficiency between the singlet spin order and magnetization, which is equal to the theoretical maximum. We anticipate that the proposed technique is useful for generating long-lived singlet order, for preserving spin hyperpolarization and for assessing singlet spin order in nearly equivalent spin pairs in specially designed molecules and in low-field NMR studies.

physics.chem-ph↗