Liu Yizhou, Cohen Ryan D, Martin Gary E, Williamson R Thomas
Structure Elucidation Group, Process and Analytical Research and Development, Merck & Co. Inc., 126 East Lincoln Avenue, Rahway, NJ 07065, USA.
Structure Elucidation Group, Process and Analytical Research and Development, Merck & Co. Inc., 126 East Lincoln Avenue, Rahway, NJ 07065, USA.
J Magn Reson. 2018 Jun;291:63-72. doi: 10.1016/j.jmr.2018.04.002. Epub 2018 Apr 7.
Accurate measurement of residual dipolar couplings (RDCs) requires an appropriate degree of alignment in order to optimize data quality. An overly weak alignment yields very small anisotropic data that are susceptible to measurement errors, whereas an overly strong alignment introduces extensive anisotropic effects that severely degrade spectral quality. The ideal alignment amplitude also depends on the specific pulse sequence used for the coupling measurement. In this work, we introduce a practical strategy for the accurate measurement of one-bond C-H RDCs up to a range of ca. -300 to +300 Hz, corresponding to an alignment that is an order of magnitude stronger than typically employed for small molecule structural elucidation. This strong alignment was generated in the mesophase of the commercially available poly-γ-(benzyl-L-glutamate) polymer. The total coupling was measured by the simple and well-studied heteronuclear two-dimensional J-resolved experiment, which performs well in the presence of strong anisotropic effects. In order to unequivocally determine the sign of the total coupling and resolve ambiguities in assigning total couplings in the CH group, coupling measurements were conducted at an isotropic condition plus two anisotropic conditions of different alignment amplitudes. Most RDCs could be readily extracted from these measurements whereas more complicated spectral effects resulting from strong homonuclear coupling could be interpreted either theoretically or by simulation. Importantly, measurement of these very large RDCs actually offers significantly improved data quality and utility for the structure determination of small organic molecules.
准确测量剩余偶极耦合（RDC）需要适当程度的取向，以优化数据质量。取向过弱会产生非常小的各向异性数据，容易受到测量误差的影响，而取向过强会引入广泛的各向异性效应，严重降低光谱质量。理想的取向幅度还取决于用于耦合测量的特定脉冲序列。在这项工作中，我们介绍了一种实用策略，用于准确测量高达约-300至+300 Hz范围内的一键C-H RDC，这对应于一种比通常用于小分子结构解析的取向强一个数量级的取向。这种强取向是在市售聚-γ-（苄基-L-谷氨酸）聚合物的中间相中产生的。通过简单且研究充分的异核二维J分辨实验测量总耦合，该实验在存在强各向异性效应的情况下表现良好。为了明确确定总耦合的符号并解决CH基团中总耦合分配的模糊性，在各向同性条件以及两种不同取向幅度的各向异性条件下进行耦合测量。大多数RDC可以很容易地从这些测量中提取出来，而由强同核耦合产生的更复杂的光谱效应可以从理论上或通过模拟进行解释。重要的是，测量这些非常大的RDC实际上为小有机分子的结构测定提供了显著提高的数据质量和实用性。
