Enhanced measurement of anisotropic NMR parameters using tunable alignment strength and tensor orientation

除了已建立的各向同性核磁共振参数，如化学位移、标量耦合和NOE，引入弱取向样品允许测量各向异性核磁共振参数，如剩余偶极耦合(RDC)。RDC的原理技术及其在分子结构测定中的巨大潜力早在1963年就已为人所知，但直到最近样品制备的发展才使RDC能够广泛用于复杂有机化合物的研究。有机化合物中的各种RDC的大小差别很大，其中2DHH和1DCH是最大的，NDCC和1DCN是最小的(最小50倍)有用的联结，这使得在不改变样品条件的情况下进行可调节的对准是非常理想的。在第一个资助期内，两种改变对准强度的技术--可变角度核磁共振和基于ELAS-TOMER的拉伸装置--已经发展到可以常规使用的程度。目前这项研究的目的是开发相应的脉冲序列，以有效地测量长程异核和碳-碳偶合。第二个目标是开发具有固定在凝胶内的液晶成分的复合对准介质，其将允许调节分子的对准张量取向，从而解决RDC的信号重叠和随机简并。开发的所有技术将首先应用于测试分子，然后用于确定天然产物和其他化学和/或生物感兴趣的分子的结构。

Next to established isotropic NMR parameters like chemical shifts, scalar couplings, and NOEs, the in-troduction of weakly oriented samples allows the measurement of anisotropic NMR parameters like re-sidual dipolar couplings (RDCs). The principle technique and its large potential in structure determination of molecules is already known since 1963 but only recent developments in sample preparation made RDCs widely available for complex organic compounds. The various RDCs in organic compounds vary substantially in size, with 2DHH and 1DCH as the largest and nDCC and 1DCN among the smallest (up to 50 times smaller) useful couplings, making an adjustable alignment without change of sample conditions highly desirable. Two techniques for varying the alignment strength, variable angle NMR and an elas-tomer-based stretching apparatus, during the first funding period have been developed to the point where they can be used routinely. The aim of the proposed research is now the development of corre-sponding pulse sequences for efficient measurement of long-range heteronuclear and carbon-carbon couplings. A second objective is pursued with the development of composite alignment media, having a liquid crystalline component fixed inside a gel, which will allow tuning of the alignment tensor orientation of molecules and thereby resolve signal overlap and random degeneracies of RDCs. All techniques de-veloped will first be applied to test molecules and then be used for the structure determination of natural products and other chemically and/or biologically interesting molecules.