Parahydrogen-Induced Hyperpolarized Nuclear Magnetic Resonance: from Basic Principle to Applications
WANG Xin-chang1, 2, JIANG Wen-long1, HUANG Cheng-da1, SUN Hui-jun1, CAO Xiao-yu2, TIAN Zhong-qun2, CHEN Zhong1, 2*
1. School of Electronic Science and Engineering, Xiamen University, Xiamen 361005, China
2. State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, and iChEM, Xiamen University, Xiamen 361005, China
Abstract：Nuclear Magnetic Resonance (NMR) can provide real-time, in-situ high-resolution molecular and biological information, and has been wildly applied in determining the structures of highly complex molecules and biological imaging. Its low sensitivity, however, hindered its further application. An effective way to increase the sensitivity of NMR is transferring hyperpolarized spin-orders of exogenous particles to the substrates. The main drawbacks of current methods are high cost of equipment and complicated procedures. Parahydrogen-induced polarization (PHIP) is a potential candidate to increase sensitivity of NMR due to its low cost, simple procedure and high polarization efficiency. By transferring the spin-order of parahydrogen into substrate, the sensitivity of NMR can be increased by at least 3 orders. This review will briefly introduce the basic principles of PHIP, physical and chemical procedures involved and its application in chemistry and biological imaging. The two hydrogen atoms in parahydrogen are in opposite spin states, and can be enriched at low temperature with the help of catalyst. Enriched parahydrogen is relatively stable even when returned to room temperature. Spin-order of parahydrogen can be transferred to substrate by two approaches. First, addition of parahydrogen into unsaturated groups in substrates, which can be used directly, or transfer spin-order to adjacent heteronucleus (13C, 15N, 19F et al). Second, signal amplification by reversible exchange (SABRE), through which parahydrogen and substrates are reversibly coordinated into metal complex and the spin-order is transferred from parahydrogen to substrates. Choosing the right catalysts is crucial for the enhancement of NMR sensitivity, and this manuscript summarized the types of catalyst used in this technique and their structures. Moreover, methods to transfer the hyperpolarized spin-order of parahydrogen, which are important for enhancing the sensitivity of heteronucleus, were also summarized. PHIP has shown great potential in many applications due to its high increase in sensitivity. First, this technique requires much lower sample concentration (μmol·L-1 or even lower) than normal NMR, which makes determination of low concentration species such as reaction intermediate or trace analysis. Second, hyperpolarized substrates are good candidates for NMR imaging contrast agent. Nevertheless, realizinglong-lived imaging contrast agent with high polarization and good solubility in water is still challenging.
Key words：Nuclear magnetic resonance; Parahydrogen-induced polarization; Imaging contrast agent; Magnetic resonance imaging contrasting agent
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