核磁共振(NMR)技术可提供原位、 实时、 高分辨的分子结构和生物组织信息, 虽然已广泛用于复杂分子结构表征和生物成像, 但低灵敏度限制了其进一步应用。 通过将外源性超极化状态核自旋转移至待测分子的原子核, 实现目标分子的超极化从而提高待测物中原子核特定自旋态的布居数差, 可有效提高NMR灵敏度。 然而, 目前主流超极化方法共同的缺点是仪器昂贵、 操作复杂。 仲氢诱导增强的超极化是一种低成本、 操作简单且高效的技术, 可将NMR灵敏度提高三个数量级以上, 正逐渐成为NMR领域的前沿热点。 介绍仲氢诱导增强超极化的基本原理、 实验方法以及在NMR谱学和成像方面的应用。 仲氢的两个氢原子核自旋方向相反, 通过降温和催化剂作用可实现高纯度富集。 富集后的仲氢通过两种方法将其超极化状态转移至底物分子。 第一种方法是在催化剂作用下将仲氢分子加成到底物分子的不饱和基团上, 直接采集氢的NMR信号, 或通过极化转移方法(脉冲序列或磁场循环)将其超极化状态转移至邻近的异核原子核(如13C, 15N, 19F等)。 第二种方法是仲氢与底物分子在金属配合物进行可逆交换反应, 实现底物分子中杂核原子的超极化。 选择合适的催化剂对灵敏度提升至关重要, 对常用催化剂的类型和结构进行了总结; 极化转移方法对异核灵敏度的提升至关重要, 并归纳了此技术中常用的极化转移方法。 仲氢诱导超极化增强技术对NMR灵敏度的显著提升使得该技术在应用方面已崭露头角。 首先, 仲氢诱导超极化增强技术将NMR谱所需浓度降低到μmol·L-1级别, 可用于表征催化反应中间体结构及监测混合物中低浓度化学物质。 其次, 基于异核的超极化底物分子是良好的NMR生物成像造影剂。 虽然仲氢超极化增强技术具有广泛的应用前景, 然而理性设计并合成超极化率高、 寿命长、 水溶性好的NMR造影剂仍是亟待解决的关键问题。

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.