Development and Application of Novel Parahydrogen based NMR Techniques

对氢是产生超极化的最有效来源之一，可用于核磁共振(核磁共振或磁共振)的灵敏度增强。使用PhIP或SABRE，将核磁共振信号提高几个数量级是可行的。然而，PhIP或Sabre类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，这一点仍然没有完全定量地理解。这种知识的缺乏对于PhIP或SABRE在结构或定量分析中的应用是一个严重的问题。因此，研究项目的第一个目标是详细分析总体上的PhIP和军刀形成，特别是深入调查副邻位转化在这一过程中的作用，因为后者可能极大地减少可能的敏感性收益。基于这一分析，将对该过程进行扩展的理论描述，并通过对模型化合物的实验进行实验验证。同时，将开发将PhIP超极化转换为净磁化的可靠和有效的技术。这种净磁化是开发有效的PhIP协议的先决条件。利用它，我们想要开发(I)超快PhIP或SABRE增强型2D-NOESY和2D-TOCSY协议，它们有可能在一次扫描中记录完整的2D-NOESY谱用于结构分析，具有前所未有的灵敏度；(Ii)用于一维和2D-核磁共振超极化从质子到异核转移的可靠技术；(Iii)在高场下用于SABRE的新的和改进的技术，即不需要场循环和(Iv)在特别设计的PhIP标记中保存通过长寿命自旋态产生的超极化的实验协议。同时，我们将继续我们在小组实验方面的工作，该小组实验允许超灵敏地检测瞬时氢催化剂络合物，并将其应用于一系列PhIP和Sabre活性催化剂。最初，所有这些技术都是在PhIP的情况下使用具有不饱和键的小模型分子或在SABRE的情况下使用简单的吡啶衍生物来开发的。稍后，我们将验证那些使用在侧链、骨骼或N-末端含有PhIP或Sabre活性基团的寡肽。

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.