Development and Application of Novel Parahydrogen based NMR Techniques

仲氢是产生超极化以增强核磁共振（NMR或MRI）灵敏度的最有效来源之一。利用PHIP或SABRE，可以将NMR信号提高几个数量级。然而，PHIP或SABRE型超极化的形成是自旋动力学和化学动力学的复杂相互作用，这仍然没有完全定量地理解。 这种知识的缺乏是PHIP或SABRE在结构或定量分析中应用的严重问题。因此，该研究项目的第一个目标是详细分析PHIP和SABRE的形成，特别是深入研究对位邻位转化在这一过程中的作用，因为后者可以大大降低可能的灵敏度增益。基于这种分析的过程中的扩展的理论描述将开发，实施和实验验证模型化合物的实验。 与此同时，将开发将PHIP超极化转换为净磁化的稳健而有效的技术。这种网络磁化是开发有效的PHP协议的先决条件。利用它，我们希望开发（i）超快速PHIP或SABRE增强的2D-NOESY和2D-TOCSY协议，其具有在单次扫描中记录完整的2D-NMR光谱以进行结构分析的潜力，具有前所未有的灵敏度;（ii）用于将超极化从质子转移到异核的1D和2D-NMR的稳健技术;（iii）用于SABRE的新的和改进的高场技术，即不需要场循环和（iv）用于通过在特别设计的PHIP标记中的长寿命自旋状态来保存所产生的超极化的实验协议。同时，我们将继续我们的工作的PANEL实验，它允许瞬态氢催化剂络合物的超灵敏检测，并将其应用到一系列的PHIP和SABRE活性催化剂。最初，所有这些技术都是采用具有不饱和键的小模型分子（在PHIP的情况下）或简单的吡啶衍生物（在SABRE的情况下）开发的。稍后，我们将验证那些采用寡肽，含有PHIP或SABRE活性基团的侧链，骨架或在N-末端。

Parahydrogen is one of the most efficient sources to generate hyperpolarization for sensitivity enhancements in nuclear magnetic resonance (NMR or MRI). With PHIP or SABRE, it is feasible to boost the NMR signals by several orders of magnitude. However, the formation of PHIP or SABRE type hyperpolarization is a complex interplay of spin dynamics and chemical kinetics, which is still not fully quantitatively understood. This lack of knowledge is a serious problem for the application of PHIP or SABRE in structural or quantitative analytics. The first target of the research project is accordingly a detailed analysis of the PHIP and SABRE formation in general and in particular an in-depth investigation of the role of para-ortho-conversions in this process, as the latter can strongly reduce the possible sensitivity gain. Based on this analysis an extended theoretical description of the process will be developed, implemented and experimentally validated by experiments on model compounds. In parallel robust and efficient techniques for the conversion of the PHIP hyperpolarization into net-magnetization will be developed. This net-magnetization is the prerequisite for the development of efficient PHIP-protocols. Employing it, we want to develop (i) ultra-fast PHIP or SABRE enhanced 2D-NOESY and 2D-TOCSY protocols, which have the potential to record a full 2D-NMR spectrum for structural analysis in a single scan with unprecedented sensitivity; (ii) robust techniques for the transfer of the hyperpolarization from the protons to heteronuclei for 1D- and 2D-NMR; (iii) new and improved techniques for SABRE at high-field, i.e. without the need of field-cycling and (iv) experimental protocols for the preservation of the created hyperpolarization via long-lived spin-states in specially designed PHIP markers. In parallel we will continue our work on the PANEL experiment, which permits the ultrasensitive detection of transient hydrogen-catalyst complexes, and apply it to a series of PHIP and SABRE active catalysts. Initially, all these techniques are develop employing small model molecules with an unsaturated bond in the case of PHIP or a simple pyridine derivate in the case of SABRE. Later we will validate those employing oligo-peptides, containing PHIP or SABRE active groups in the side chain, the back-bone or at the N-terminus.