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Hyperpolarized Molecules for Applications in Chemistry and Biomedicine

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Applied Chemistry".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 18250

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Special Issue Editor

Dr. Danila Barskiy

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Guest Editor

1. GSI Helmholtzzentrum für Schwerionenforschung, Helmholtz-Institut Mainz, 55128 Mainz, Germany
2. Institut für Physik, Arbeitsgruppe Quanten-, Atom- und Neutronenphysik (QUANTUM), Johannes Gutenberg-Universität Mainz, 55128 Mainz, Germany
Interests: NMR; MRI; hyperpolarization; nuclear spin dynamics; chemical kinetics; catalysis

Special Issue Information

Dear Colleagues,

Nuclear magnetic resonance spectroscopy (NMR) and imaging (MRI) are among the most powerful analytical tools used to study chemical and biochemical transformations. However, one of the main drawbacks of NMR and MRI is their low sensitivity. Hyperpolarization techniques allow enhancing the NMR signals of various molecules by several orders of magnitude, making possible applications that were previously inaccessible, i.e., monitoring metabolism of small molecules in vivo.

Researchers working in the field of hyperpolarized NMR/MRI are invited to contribute original research papers or reviews to this Special Issue of Molecules, which will report on the chemistry and physics of hyperpolarization formation, improvements in the detection of hyperpolarized molecules, and applications of hyperpolarized NMR/MRI approaches in chemistry and biomedicine.

Dr. Danila Barskiy
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hyperpolarization
nuclear magnetic resonance
magnetic resonance imaging
metabolism
cancer
bioprobes

Published Papers (6 papers)

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Research

Jump to: Review

17 pages, 1630 KiB

Open AccessArticle

Functionalized Controlled Porous Glasses for Producing Radical-Free Hyperpolarized Liquids by Overhauser DNP

by Raphael Kircher, Sarah Mross, Hans Hasse and Kerstin Münnemann

Molecules 2022, 27(19), 6402; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27196402 - 28 Sep 2022

Cited by 1 | Viewed by 1303

Abstract

Overhauser dynamic nuclear polarization (ODNP) can be used as a tool for NMR signal enhancement and happens on very short time scales. Therefore, ODNP is well suited for the measurement of fast-flowing samples, even in compact magnets, which is beneficial for the real-time monitoring of chemical reactions or processes. ODNP requires the presence of unpaired electrons in the sample, which is usually accomplished by the addition of stable radicals. However, radicals affect the nuclear relaxation times and can hamper the NMR detection. This is circumvented by immobilizing radicals in a packed bed allowing for the measurement of radical-free samples when using ex situ DNP techniques (DNP build-up and NMR detection happen at different places) and flow-induced separation of the hyperpolarized liquid from the radicals. Therefore, the synthesis of robust and chemically inert immobilized radical matrices is mandatory. In the present work, this is accomplished by immobilizing the radical glycidyloxy-tetramethylpiperidinyloxyl with a polyethyleneimine (PEI) linker on the surface of controlled porous glasses (CPG). Both the porosity of the CPGs and also the size of the PEI-linker were varied, resulting in a set of distinct radical matrices for continuous-flow ODNP. The study shows that CPGs with PEI-linkers provide robust, inert and efficient ODNP matrices. Full article

(This article belongs to the Special Issue Hyperpolarized Molecules for Applications in Chemistry and Biomedicine)

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9 pages, 1386 KiB

Open AccessCommunication

Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives

by Kerti Ausmees, Nele Reimets and Indrek Reile

Molecules 2022, 27(3), 802; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27030802 - 26 Jan 2022

Cited by 7 | Viewed by 2274

Abstract

Parahydrogen hyperpolarization has emerged as a promising tool for sensitivity-enhanced NMR metabolomics. It allows resolution and quantification of NMR signals of certain classes of low-abundance metabolites that would otherwise be undetectable. Applications have been implemented in pharmacokinetics and doping drug detection, demonstrating the versatility of the technique. Yet, in order for the method to be adopted by the analytical community, certain limitations have to be understood and overcome. One such question is NMR signal assignment. At present, the only reliable way to establish the identity of an analyte that gives rise to certain parahydrogen hyperpolarized NMR signals is internal standard addition, which can be laborious. Herein we show that analogously to regular NMR metabolomics, generating libraries of hyperpolarized analyte signals is a viable way to address this limitation. We present hyperpolarized spectral data of adenosines and give an early example of identifying them from a urine sample with the small library. Doing so, we verify the detectability of a class of diagnostically valuable metabolites: adenosine and its derivatives, some of which are cancer biomarkers, and some are central to cellular energy management (e.g., ATP). Full article

(This article belongs to the Special Issue Hyperpolarized Molecules for Applications in Chemistry and Biomedicine)

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14 pages, 1094 KiB

Open AccessArticle

Rapid SABRE Catalyst Scavenging Using Functionalized Silicas

by Thomas B. R. Robertson, Leon J. Clarke and Ryan E. Mewis

Molecules 2022, 27(2), 332; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27020332 - 06 Jan 2022

Cited by 4 | Viewed by 2852

Abstract

In recent years the NMR hyperpolarisation method signal amplification by reversible exchange (SABRE) has been applied to multiple substrates of potential interest for in vivo investigation. Unfortunately, SABRE commonly requires an iridium-containing catalyst that is unsuitable for biomedical applications. This report utilizes inductively coupled plasma-optical emission spectroscopy (ICP-OES) to investigate the potential use of metal scavengers to remove the iridium catalytic species from the solution. The most sensitive iridium emission line at 224.268 nm was used in the analysis. We report the effects of varying functionality, chain length, and scavenger support identity on iridium scavenging efficiency. The impact of varying the quantity of scavenger utilized is reported for the three scavengers with the highest iridium removed from initial investigations: 3-aminopropyl (S₁), 3-(imidazole-1-yl)propyl (S₄), and 2-(2-pyridyl) (S₅) functionalized silica gels. Exposure of an activated SABRE sample (1.6 mg mL⁻¹ of iridium catalyst) to 10 mg of the most promising scavenger (S₅) resulted in <1 ppm of iridium being detectable by ICP-OES after 2 min of exposure. We propose that combining the approach described herein with other recently reported approaches, such as catalyst separated-SABRE (CASH-SABRE), would enable the rapid preparation of a biocompatible SABRE hyperpolarized bolus. Full article

(This article belongs to the Special Issue Hyperpolarized Molecules for Applications in Chemistry and Biomedicine)

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Graphical abstract

10 pages, 1965 KiB

Open AccessArticle

Hyperpolarization of Nitrile Compounds Using Signal Amplification by Reversible Exchange

by Sarah Kim, Sein Min, Heelim Chae, Hye Jin Jeong, Sung Keon Namgoong, Sangwon Oh and Keunhong Jeong

Molecules 2020, 25(15), 3347; https://doi.org/10.3390/molecules25153347 - 23 Jul 2020

Cited by 7 | Viewed by 2268

Abstract

Signal Amplification by Reversible Exchange (SABRE), a hyperpolarization technique, has been harnessed as a powerful tool to achieve useful hyperpolarized materials by polarization transfer from parahydrogen. In this study, we systemically applied SABRE to a series of nitrile compounds, which have been rarely investigated. By performing SABRE in various magnetic fields and concentrations on nitrile compounds, we unveiled its hyperpolarization properties to maximize the spin polarization and its transfer to the next spins. Through this sequential study, we obtained a ~130-fold enhancement for several nitrile compounds, which is the highest number ever reported for the nitrile compounds. Our study revealed that the spin polarization on hydrogens decreases with longer distances from the nitrile group, and its maximum polarization is found to be approximately 70 G with 5 μL of substrates in all structures. Interestingly, more branched structures in the ligand showed less effective polarization transfer mechanisms than the structural isomers of butyronitrile and isobutyronitrile. These first systematic SABRE studies on a series of nitrile compounds will provide new opportunities for further research on the hyperpolarization of various useful nitrile materials. Full article

(This article belongs to the Special Issue Hyperpolarized Molecules for Applications in Chemistry and Biomedicine)

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16 pages, 1455 KiB

Open AccessArticle

In Situ SABRE Hyperpolarization with Earth’s Field NMR Detection

by Fraser Hill-Casey, Aminata Sakho, Ahmed Mohammed, Matheus Rossetto, Fadi Ahwal, Simon B. Duckett, Richard O. John, Peter M. Richardson, Robin Virgo and Meghan E. Halse

Molecules 2019, 24(22), 4126; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224126 - 14 Nov 2019

Cited by 7 | Viewed by 4009

Abstract

Hyperpolarization methods, which increase the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), have the potential to expand the range of applications of these powerful analytical techniques and to enable the use of smaller and cheaper devices. The signal amplification by reversible exchange (SABRE) method is of particular interest because it is relatively low-cost, straight-forward to implement, produces high-levels of renewable signal enhancement, and can be interfaced with low-cost and portable NMR detectors. In this work, we demonstrate an in situ approach to SABRE hyperpolarization that can be achieved using a simple, commercially-available Earth’s field NMR detector to provide ¹H polarization levels of up to 3.3%. This corresponds to a signal enhancement over the Earth’s magnetic field by a factor of ε > 2 × 10⁸. The key benefit of our approach is that it can be used to directly probe the polarization transfer process at the heart of the SABRE technique. In particular, we demonstrate the use of in situ hyperpolarization to observe the activation of the SABRE catalyst, the build-up of signal in the polarization transfer field (PTF), the dependence of the hyperpolarization level on the strength of the PTF, and the rate of decay of the hyperpolarization in the ultra-low-field regime. Full article

(This article belongs to the Special Issue Hyperpolarized Molecules for Applications in Chemistry and Biomedicine)

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Review

Jump to: Research

96 pages, 9298 KiB

Open AccessReview

Molecular Sensing with Host Systems for Hyperpolarized ¹²⁹Xe

by Jabadurai Jayapaul and Leif Schröder

Molecules 2020, 25(20), 4627; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25204627 - 11 Oct 2020

Cited by 19 | Viewed by 4046

Abstract

Hyperpolarized noble gases have been used early on in applications for sensitivity enhanced NMR. ¹²⁹Xe has been explored for various applications because it can be used beyond the gas-driven examination of void spaces. Its solubility in aqueous solutions and its affinity for hydrophobic binding pockets allows “functionalization” through combination with host structures that bind one or multiple gas atoms. Moreover, the transient nature of gas binding in such hosts allows the combination with another signal enhancement technique, namely chemical exchange saturation transfer (CEST). Different systems have been investigated for implementing various types of so-called Xe biosensors where the gas binds to a targeted host to address molecular markers or to sense biophysical parameters. This review summarizes developments in biosensor design and synthesis for achieving molecular sensing with NMR at unprecedented sensitivity. Aspects regarding Xe exchange kinetics and chemical engineering of various classes of hosts for an efficient build-up of the CEST effect will also be discussed as well as the cavity design of host molecules to identify a pool of bound Xe. The concept is presented in the broader context of reporter design with insights from other modalities that are helpful for advancing the field of Xe biosensors. Full article

(This article belongs to the Special Issue Hyperpolarized Molecules for Applications in Chemistry and Biomedicine)

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