Selective hyperpolarization of heteronuclear singlet states via pulsed microtesla SABRE

Tanner, Christian; Lindale, Jacob R.; Eriksson, Shannon L.; Zhou, Zijian; Colell, Johannes F. P.; Theis, Thomas; Warren, Warren S.

doi:10.1063/1.5108644

Cited by 22 publications

(25 citation statements)

References 21 publications

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“…In this context, SABRE does not require harsh conditions, and substrates can be constantly hyperpolarized without any structural changes during the polarization transfer. Furthermore, in this method, the polarization can be real-time transferred from protons to other isotopes such as 13 C 19 , 15 N 20 – 23 , 31 P 24 , 19 F 25 , 119 Sn 26 , and 29 Si 27 without chemical changes.…”

Section: Introductionmentioning

confidence: 99%

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Jeong

Min

Chae

et al. 2020

Sci Rep

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Several drug candidates have been proposed and tested as the latest clinical treatment for coronavirus pneumonia (COVID-19). Chloroquine, hydroxychloroquine, ritonavir/lopinavir, and favipiravir are under trials for the treatment of this disease. The hyperpolarization technique has the ability to further provide a better understanding of the roles of these drugs at the molecular scale and in different applications in the field of nuclear magnetic resonance/magnetic resonance imaging. This technique may provide new opportunities in diagnosis and research of COVID-19. Signal amplification by reversible exchange-based hyperpolarization studies on large-sized drug candidates were carried out. We observed hyperpolarized proton signals from whole structures, due to the unprecedented long-distance polarization transfer by para-hydrogen. We also found that the optimal magnetic field for the maximum polarization transfer yield was dependent on the molecular structure. We can expect further research on the hyperpolarization of other important large molecules, isotope labeling, as well as polarization transfer on nuclei with a long spin relaxation time. A clinical perspective of these features on drug molecules can broaden the application of hyperpolarization techniques for therapeutic studies. Coronavirus pneumonia (COVID-19) is a serious respiratory infectious disease that has emerged recently. Patients with coronavirus infection demonstrate fever with body temperature exceeding 38 °C, and symptoms, such as dry cough, fatigue, dyspnea, difficulty in breathing, and frosted glass-like symptoms in the lungs 1. The disease is known to be highly transmittable without the occurrence of severe symptoms. The number of cases has reached over tens of millions worldwide. To overcome this pandemic, many researchers have started working on developing a vaccine. However, ongoing vaccine developments are estimated to take over a year before becoming available for public use. As a result, the global clinical community is attempting to repurpose existing drugs to tackle the COVID-19 crisis. Recently, several drugs that can inhibit specific functions of the virus have been proposed and tested as part of the latest clinical treatment approaches. These drugs include chloroquine and hydroxychloroquine. Although the role of these drugs in the treatment of COVID-19 is controversial, hydroxychloroquine is more soluble than chloroquine and produces relatively less toxic metabolites 2-4. Although chloroquine (7-chloro-4-(4-diethylamino-1-methylbutylamino)-quinoline) and hydroxychloroquine (2-[4-[(7-chloroquinolin-4-yl)amino]pentylethylamino]ethanol), which have been in clinical usage for the last seventy years, are drugs for the treatment of autoimmune disease, they are also used as antimalarial drugs. These compounds have recently been reported as potential broad-spectrum antiviral drugs for COVID-19 5 ; however, their benefits against COVID-19 are controversial, with no evident effect on hospitalized patients 6. From a molecular perspective, the...

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Section: Introductionmentioning

confidence: 99%

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Jeong

Min

Chae

et al. 2020

Sci Rep

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“…More importantly, it is expected to be used for tracking the hyperpolarized signal through MRI in future studies. Examples include isotope labeling (such as carbon to 13 C isotope and nitrogen into 15 N) in the structure of chloroquine and lopinavir, which might have a long T1 time. This is not just because of the lower gyromagnetic ratio, but also because of its smaller relaxation effect from the Ir-catalyst by short binding time due to its relatively unstable complex structure.…”

Section: Resultsmentioning

confidence: 99%

“…Of several methods to hyperpolarize drugs, the para-hydrogen based signal amplification by reversible exchange (SABRE) method is a promising tool for hyperpolarization of several key structures with nitrogen. Furthermore, its polarization could be transferred in real time from protons to other isotopes such as 13 Several great recent studies of producing hyperpolarized drugs or metabolites [16][17][18][19][20] , including pharmacokinetics using SABRE 21 , confirm that such a study would widen its application in this era, when scientific solutions are the only way to conquer this disaster. Therefore, a hyperpolarization study using SABRE may be a good and key start to applying MRI scanning by using hyperpolarized chloroquine/lopinavir in the future.…”

Section: Introductionmentioning

confidence: 99%

Chloroquine and Lopinavir (COVID-19 Drug Candidates) Signal Amplification by Reversible Exchange

HyeJin¹,

Min²,

Chae³

et al. 2020

Preprint

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<p>To overcome the recent coronavirus pneumonia (COVID-19), several drug candidates are suggested and tested for the latest clinical treatment. Chloroquine and lopinavir are showing definite effects after treatment. To understand more about those roles in molecular level and future application on NMR/MRI, hyperpolarization technique can open new opportunities in the diagnosis and biomedical researches to cope with COVID-19. SABRE-based hyperpolarization studies on those two drug candidates are carried out and we observed hyperpolarized proton signals from the whole structures, which can be possible by unprecedented long-distance polarization transfer by <i>para</i>-hydrogen. Base on this result, future work on isotope labeling, and further polarization transfer on long T1 time nuclei including clinical perspectives will open a new door for overcoming this dreadful catastrophe.</p>

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“…To emphasize the efficiency and flexibility of this framework, we used the DMExFR2 model to fit the coherent hyperpolarization dynamics of ( 15 N-13 C)-acetonitrile when exciting the sample with short (milisecond) pulses tuned to a field near the SABRE resonance condition, as described in our prior work (5,32). Coherent evolution is then interrogated by varying the resonant pulse length, which encodes the dynamics in the final polarization detected.…”

Section: A B Cmentioning

confidence: 99%

Infinite-order perturbative treatment for quantum evolution with exchange

et al. 2020

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Many important applications in biochemistry, materials science, and catalysis sit squarely at the interface between quantum and statistical mechanics: Coherent evolution is interrupted by discrete events, such as binding of a substrate or isomerization. Theoretical models for such dynamics usually truncate the incorporation of these events to the linear response limit, thus requiring small step sizes. Here, we completely reassess the foundations of chemical exchange models and redesign a master equation treatment for exchange accurate to infinite order in perturbation theory. The net result is an astonishingly simple correction to the traditional picture, which vastly improves convergence with no increased computational cost. We demonstrate that this approach accurately and efficiently extracts physical parameters from complex experimental data, such as coherent hyperpolarization dynamics in magnetic resonance, and is applicable to a wide range of other systems.

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Selective hyperpolarization of heteronuclear singlet states via pulsed microtesla SABRE

Cited by 22 publications

References 21 publications

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Signal amplification by reversible exchange for COVID-19 antiviral drug candidates

Chloroquine and Lopinavir (COVID-19 Drug Candidates) Signal Amplification by Reversible Exchange

Infinite-order perturbative treatment for quantum evolution with exchange

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