Fast and Robust Two-Dimensional Heteronuclear Correlation Experiments for Small Molecules

多维高分辨核磁共振波谱是现代化学中最重要的分析方法之一。特别是二维异相关联实验是可靠表征溶液中分子和复杂混合物的基本要素。然而，相应实验的长测量时间导致严重的限制，并阻止其在许多应用中的使用。基于ASAP和ALSOFAST-HSQC的概念，我们的目标是在拟议的项目中开发和优化一系列具有不同目标的非常快速的异质结相关实验。为了实现这一目标，有必要了解所产生的信号强度的决定因素，将开发和实验验证的参数的系统变化的基础上的一些模型。然后，快速实验将以两种一般的方式进行扩展：一方面，ASAP和ALSOFAST概念将分别包括在许多已建立的脉冲序列中，如HSQC-TOCSY，纯移位HSQC，ADEQUATE，HSQC-DOSY和HMBC;另一方面，ASAP-HSQC作为实验的基本元素，将在鲁棒性，灵敏度，和解耦的可能性。特别是这些优化也将导致许多常规实验的改进。最后，快速实验的适用性将显示为各个研究领域。相应序列的使用将在NMR服务和代谢组学应用、质量控制和流动NMR以及扩散NMR中得到证明。

Multidimensional high resolution NMR spectroscopy is among the most important analytical methods in modern chemistry. Especially two-dimensional heteronuclear correlation experiments are an essential element for a reliable characterization of molecules and complex mixtures in solution. However, long measurement times of the corresponding experiments lead to severe limitations and prevent their use in many applications. Based on the concept of the ASAP- and ALSOFAST-HSQC, we aim in the proposed project to develop and optimize a series of very fast heteronuclear correlation experiments with different objectives. For this goal it is essential to understand the determining factors for resulting signal intensities, for which a number of models based on systematic variations of parameters will be developed and experimentally verified. The fast experiments will then be extended in two general ways: on the one hand, the ASAP- and ALSOFAST-concept, respectively, will be included in a number of well-established pulse sequences like the HSQC-TOCSY, pure shift HSQC, ADEQUATE, HSQC-DOSY, and HMBC; on the other hand, the ASAP-HSQC as the basic element of the experiments, will be further optimized with respect to robustness, sensitivity, and possibilities for decoupling. Especially these optimizations will also lead to improvements for many conventional experiments. Finally, the applicability of the fast experiments will be shown for various research areas. The use of corresponding sequences will be demonstrated in NMR service and metabolomics applications, quality control and flow-NMR as well as diffusion-NMR.