Development and Application of Novel Parahydrogen based NMR Techniques

对氢是在核磁共振（NMR或MRI）中产生超极化以增强灵敏度的最有效来源之一。使用PHIP或SABRE，可以将核磁共振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，目前还没有完全定量理解。这种知识的缺乏对于php或SABRE在结构或定量分析中的应用来说是一个严重的问题。因此，研究项目的第一个目标是对PHIP和SABRE形成进行详细分析，特别是对这一过程中对正交转换的作用进行深入研究，因为后者可以大大降低可能的灵敏度增益。在此分析的基础上，对该过程进行了扩展的理论描述，并通过模型化合物的实验进行了实现和实验验证。同时，将开发将PHIP超极化转化为净磁化的可靠而有效的技术。这种网络磁化是开发高效的php协议的先决条件。采用它，我们希望开发(i)超快速PHIP或SABRE增强的2d - noasy和2D-TOCSY协议，这些协议有可能在单次扫描中以前所未有的灵敏度记录完整的2D-NMR光谱进行结构分析；（ii）一维和二维核磁共振超极化从质子转移到异核的可靠技术；（iii）新的和改进的高场SABRE技术，即不需要场循环；（iv）在专门设计的PHIP标记物中通过长寿命自旋态保存所创建的超极化的实验方案。与此同时，我们将继续开展PANEL实验，该实验允许超灵敏地检测瞬态氢催化剂配合物，并将其应用于一系列PHIP和SABRE活性催化剂。最初，所有这些技术都是使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，在侧链，骨干或n端含有PHIP或SABRE活性基团的人。

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.